, Ahmed Kotb, MD, discussed findings from a trial investigating navitoclax for the treatment of myelofibrosis. In safety findings from the trial, thrombocytopenia was the most common adverse effect, which was managed through dose reduction.

Q: What were the most common adverse effects and how severe were these?

I think it's important to look at the holistic data set. I think it's important to see the efficacy as well as the safety together. And let's look at the cohort 3. This is the cohort where navitoclax was added to ruxolitinib in the JAK-naive patient population. The primary endpoint, as I mentioned, was SVR35. And here, what we saw was about 63% of the patients achieved this endpoint at the 6-month landmark, as I mentioned, 24 weeks. This is quite unprecedented in this disease area.

What we also saw was that the longer you treated patients, more patients responded. So, we saw best overall response in about 78%. Again, this is very encouraging for us. We have a phase 3 trial that's ongoing, that is looking exactly at that, adding navitoclax-ruxolitinib versus ruxolitinib alone, so we're quite excited to see the outcomes of that study, because we believe this may be practice changing. At the same time, the other endpoints, like total symptom score reduction was about 40%. Again, very encouraging. We also saw that about a third of the patients showed a reduction in the bone marrow fibrosis. And what was very interesting was that irrespective of the amount of fibrosis the patient had at baseline, whether it was a lot of fibrosis or intermediate or a little amount of fibrosis, they had the chance to decrease this bone marrow fibrosis. So that was about 35%. So, that was also quite interesting and gives us the confidence that this agent may be having a disease modification potential.

From a side effect perspective, from an adverse event perspective, the most common adverse event was thrombocytopenia, it occurred in about 80% of the patients. It's an on-target side effect because BCL-XL, which is the target of navitoclax, is highly expressed on thrombocytopenia, thrombocytes, or platelets. So, we expected that it's a predictable and manageable adverse event. We didn't see any clinically meaningful bleeds happen in the study.

Q: How can these adverse effects be managed?

So, so far, we have not really seen that this adverse event has impacted the outcomes of therapy. It's kind of included within the outcomes that I've just mentioned. The way we manage it within the protocol is we do reduce the dose and when it gets to a certain level, we sometimes dose interrupt. We still keep baseline therapy, which is ruxolitinib. It's also important to know that thrombocytopenia is a side effect of both the agents, navitoclax and ruxolitinib, so there is an algorithm of how this is being managed.

Q: Is there anything you would like to add?

No, I think this is very exciting. I think that this is a new mechanism of action in a disease area that has not seen much advances over the last decades. I think we're quite hopeful that this molecule will add options to patients and to physicians. As I mentioned, we have a phase 3 trial, the TRANSFORM-1, which is running in the frontline setting. We also have a phase 3 trial that is running in the relapsed/refractory setting. We're hoping to see data from these studies by end of this year, early next year, and we will use this data to register navitoclax and hopefully bring it to patients in need. This also shows the investment that AbbVie is doing in oncology and the way we're trying to drive innovations across multiple blood cancers. We've obviously done a lot in CLL with venetoclax and IMBRUVICA. We're doing a lot also in AML with venetoclax, and we're expanding our portfolio to touch other blood cancers like lymphomas with epcoritamab, we have exciting data coming at EHA, and also you're going to see data here at ASCO from our solid tumor program. So, it really speaks to the breadth of our oncology portfolio and how we're evolving that.

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Thrombocytopenia was the most common adverse effect, which was managed through dose reduction.

Manage Adverse Effects Associated With Navitoclax in Patients With Myelofibrosis

 interviewed Zahra Mahmoudjafari, PharmD, BCOP, DPLA; Alison Gulbis, PharmD, BCOP; and Kamakshi Rao, PharmD, BCOP, FASHP, on a 2022 ATOPP Summit session they will be co-presenting addressing research they conducted assessing the underlying causes of the hematology-oncology pharmacist great migration.

 Where are hematology-oncology pharmacists migrating to for the most part?

 Well, that is a great question. That's not something we could pull out from the survey, but speaking from what we know of people going, I'd say a lot of them went into pharmaceutical industry, especially with the increase in CAR-T products and other opportunities out there that were opening up for medical science liaison positions, etc. I think a lot of people have gone to that.

But in addition to that, there have been a lot of other nontraditional pharmacy roles that have opened up that people with clinical expertise really are being recruited for. That includes things like working for insurance companies, as a clinical pharmacist to help with decisions they may have to make with formularies or other access issues patients might have. There's health information technology, tons of people are looking for clinical pharmacists to help with the sector of the electronic health record [(EHR)] and how to build orderable, especially for chemotherapy, etc, and best practices and data mining, and looking at how do you pull data and extract it out of the EHR and bring it back to take care of the patient better.

So those are some nontraditional roles that I think are becoming more appealing to people also, because they're remote positions, for the most part. So I think those will be trends that continue. You may see a more equal shift across different types of positions that might be out there, not just industry.

 I would definitely echo that what we saw in our research, we have to absolutely acknowledge that our colleagues are well-trained and well-positioned to take on these roles, and that the title of clinical pharmacist is evolving.

There's also, to add to what Alison said, opportunities in continuing education, and some of our colleagues have moved onto support those types of roles. So there's no shortage of opportunities, and I have to acknowledge, that doesn't necessarily mean that clinical pharmacists are going to necessarily be in direct patient care roles like we were when we were training.

 Has there been any research conducted looking to assess this migration from the field?

 So there's a lot of research on burnout in health care professionals, and pharmacists get lumped into that in a lot of those surveys that have been done within the past 5 to 10 years. I think that what hasn't been addressed directly in terms of a study is how do you mitigate these migration issues, how do you keep and retain your employees, and how do you come up with ways to show that you appreciate them that you recognize their hard work their doing and that you're willing to give them time to do professional development activities.

There's commentary on that in some publications, but how do you make that go into play and how do you measure if that works to keep employees. That hasn't been research that's been done that I've been able to find.

 Yeah, I would say that was that was the motivation here is that we've had those anecdotal stories, we've heard the commentary, and we've read the opinion papers, but what we really thought was there's power that could be had if we could aggregate that data and start to show that it's not an institutional issue, it's not a regional issue; it's a nationwide professional issue. So that was really the goal when we started was to make sure that every oncology pharmacist in the country had a voice that we could aggregate together to show some power, and I think that's exactly what we saw in the study.

In that survey that we sent out we asked some directed questions around job satisfaction, around how that correlated with a desire to consider alternate careers or changing careers, but then we actually left an open commentary section, and that was the part that I think when we got results, I sent Zarah and Alison an email saying we have a couple of hours or days of reading ahead of us, because people just bared their souls, and it was so powerful to read those words.

As we started to really affinitize that data, it was so clear that it was common themes coming across consistently, so as 3 of us really sat and all 3 of us have read all the comments, we feel really confident that this is a really powerful way of looking at this data as a whole. So ours is just one piece that I would say warrants repetition throughout the pharmacy profession.

Is this migration occurring across the field among hematology-oncology professionals beyond pharmacy, or is it primarily occurring among pharmacists?

 I'd say yes, it is occurring across health care, not just hematology/oncology. I think even beyond health care, when you read articles about the “Great Resignation,” they don't focus just on health care professionals.

It's hard to pinpoint if, like we said earlier, is this because of the pandemic and all the things that occurred with it. Clearly, something has happening for people to notice it and talk about it, whether it be through a commentary in the 

 or other places where they're talking about this, but yeah, I think it's an issue across the board.

It might be that maybe we need to revisit all human professionals or all health care professionals, and are they doing what they should do at the top of their license? Do we need to make sure we're not giving administrative tasks to people who shouldn't be getting certain administrative tasks? Do we need to make sure we're giving protected time to all these people to develop professionally, because professional development is vital in health care in general, to make sure that you're on top of things, and you're in the know, with the new research and that you're networking with people. I think that was a big thing COVID-19 took away from us to networking with people. That's made an impact on how people rethink what they're doing across health care, and is this what they want doing and be in?

What is your outlook on the future for hematology-oncology pharmacy?

 That's a big question because there's a lot of weight behind that answer. But, quite honestly, I've been a hematology/oncology pharmacist for over 20 years now, and I remain optimistic about the impact and the value that hematology/oncology pharmacy professionals and pharmacists can have.

It is so clear the value that we have in helping optimize patient care and collaborating with our other health care providers and professionals to do strong research to teach and to advance care. Those opportunities all exist, and they will continue to grow over time. As all 3 of us are involved heavily in education as well, it's great to see the amount of interest there is in joining this profession and being part of that.

I would say there's a challenge to the profession as well. I think it is going to require local institutions and our profession as a whole to really embark on some very serious cultural change: It's about changing our value proposition and it's about trying to blend the business-minded pharmacy with the idea that we are a people-oriented profession, not just for our patients, but for the people that actually do the work. I think that the evolving focus and the evolving attention around building inclusive work environments is absolutely necessary to be leaned into.

So I think there is a challenge ahead for those that are trying to leave this profession to make it one that continues to be someplace that people choose to join, and maybe more importantly, a place that people choose to stay. I think a lot of people see clinical practice as that first entry point out of postgraduate training, our challenge is going to be how do we get them to see it as a place where they can continue to grow and evolve for a long swath of their career.

 Well, I feel like we've laid a lot out the issues and the problems, but I think there's also strategies to mitigate and make things better. So I don't think we want to leave this all doom and gloom. I think there's great promise for us.

I think from a mitigation and how do we move this in the right direction standpoint, I think it's a couple of things, and I invite my co-authors here to chime in. I think, on one hand, is just recognition that the landscape of opportunity has changed and supporting our people so that every individual has the opportunity to realize their best potential, whether that be within the patient care environment or outside is part of our job to move people into the roles that they best deserve.

I think a lot of times people migrating into roles outside of direct patient care, we've all heard the terms people say, 

‘Oh, they're moving to the dark side of admin or the dark side of industry.’

 Realistically, there are just so many sides, so I am more interested in people finding where they belong versus feeling like they are running from jobs that aren't satisfying and that don't have the right reward ratio.

I think individuals have a responsibility to communicate with their managers and managers have a responsibility to open, vulnerable, and thoughtful conversations with employees so you can understand what each individual is looking for. If we can really engage in getting to know the people who are helping us deliver care, then there's nothing that we can't do and there's nothing that we can't get past.

 Well, I agree, I would say we have an opportunity now. We understand the issue, we understand what it is our team members are asking for, so I think, as practice managers, we have to continue to advocate for, like Kamakshi said, our value, not only within our organizations but within ourselves, but also outside of our departments, with our providers, with our nursing colleagues, etc so they can give support to our pharmacists that are with us and are working day in and day out, trying to make their lives a little bit easier, giving them that time that they need to do the teaching, do the research, supporting them in whatever support means to them. And then recognizing that patient care is extra ordinary, it should not be ordinary, and making sure that they feel valued as well.

We also have an opportunity, as Kamakshi said, to figure out this value metric and apply it to clinical pharmacy in a way that's meaningful and not just institutionally specific, as that's something we definitely have yet to define from a clinical pharmacy standpoint. So I see opportunity to talk about this, and we've looked up the data and now we need to work on the next steps. So we're really looking forward to the discussion in San Diego and presenting the research. It's near and dear to us so it’s a exciting to present it because we've been sitting on it for a little bit and we're really excited to show it off and to really start the discussion with everyone.

Zahra Mahmoudjafari, PharmD, BCOP, DPLA; Alison Gulbis, PharmD, BCOP; and Kamakshi Rao, PharmD, BCOP, FASHP, discuss research conducted looking to assess the hematology-oncology pharmacist “great migration” from the field.

Expert: The Great Migration of Hematology, Oncology Pharmacists Brings a Call to Action for the Field

 interviewed Ken Thorpe, PhD, professor of public health at Emory University and chairman of Partnership to Fight Chronic Disease, on legislation that the US House of Representatives passed to put greater restrictions on the FDA’s accelerated approval pathway.

. Joining me is Ken Thorpe, a professor of public health at Emory University and a chairman of the Partnership to Fight Chronic Disease. Ken is here to discuss legislation that the US House of Representatives just passed to put greater restrictions on the FDA’s accelerated approval pathway.

So Ken, what is this legislation and what exactly does it restrict?

 Well, it's a piece of legislation that passed the House has yet to pass through the Senate. But in essence, what it’s saying is that it gives the Secretary broad authority to require, prior to approval in the program, that a drug go through a post-approval study. So at least have that setup.

Also it does give the Secretary the flexibility to not require one, and if it's not required, they would have to publish the reason why under the FDA website, given the rationale for it. So it's really just tightening up this process of really the post-approval confirmatory studies.

 You mentioned, just as a follow up, the Secretary—is the Secretary someone within the FDA or someone appointed by legislators?

 No, it would be over at the FDA. So it would be an FDA decision in terms of how this goes. The idea is to really, as the drug is getting approved, that there'd be a methodology laid out, enrollment targets, really the structure of the post-approval study process would have to be sitting there. Then the company, the manufacturer would have to provide some indication of progress within 180 days after the accelerated approval has been okayed.

So I think there was some concern that some of these medications that went through the accelerated approval process or not, on a timely basis, really going through the more formal confirmatory studies, although, again, most of them did, so approximately 80% of the drugs that are approved through the accelerated approval process, ultimately are approved through the traditional FDA evaluation method.

 Does the passing of this legislation in the House result in any immediate action or does that not take place until the Senate makes a decision?

 Yeah, no, there's no immediate action. We're going to have to wait on the Senate to pass their version. This is on the FDA user fee program, so there's some urgency to get it passed by next fiscal year on October 1. But the versions are somewhat different though, on the non-FDA user fee components. So they're going to have to come up with a reconciliation of sorts, to get both of the bills to match up on the language with this accelerated approval process. So no immediate action now.

 Why was the FDA’s accelerated approval pathway developed in the first place, and what have been the results of its development to date?

 Well, it was approved some time ago, really in response to the HIV/AIDS epidemic. At that time, obviously, that was a disease that we really had no treatment options for and the mortality rates, obviously, were very, very high. So the FDA put into place a process that they could get medications and treatments out to HIV/AIDS patients in a much faster time period, just given the seriousness of that illness. So, it has been incredibly successful, particularly for cancer patients and patients with rare diseases.

The process started in 1992, and there's been over 270 treatments that have been approved since then. So, I think the results have been impressive. There's been a reduction in cancer mortality deaths since 1992. Those types of medications, whether they be cancer or rare disease drugs, come to market a little over 3 years faster than they otherwise would. So it's really a critically important part of treating patients that have maybe limited, if no other, treatment options.

 What are the arguments being made by the critics of the FDA is accelerated approval pathway, and is there any validity to these arguments?

 Well, the argument that I hear most frequently is that the process is expensive, and that these medications are costing, particularly Medicaid programs, a lot of money. So we've spent a lot of time looking at that issue, just to see what role accelerated approval drugs play in the Medicaid budget and in the growth of Medicaid spending.

We've gone back to 2007 looking at this, and what we have found is that the growth of accelerated approval drug spending accounts for less than one half of 1% of the growth in Medicaid spending, and in any particular year, they account for less than one half of 1% of the total Medicaid budget. So I think that this criticism and concern of the program is really unfounded, they really don't consider they'll contribute to the growth and level of Medicaid spending.

We know that Medicaid expenditures are driving up because of increased enrollment, but also because they have to provide treatment to really expensive patients, disabled patients, that are eligible for both Medicare and Medicaid. That's where most of the spending is—roughly 40% of the Medicaid budget goes to treating those types of patients. So I think if we're really serious about slowing the growth in Medicaid spending, that we really need to look at what's driving it in the first place and the accelerated approval drugs or not.

 As a follow up question, do you believe or think that the impact of vaccine hesitancy that really emerged as a key problem during the pandemic in terms of vaccine uptake that that might have some role in this decision or this legislation that just passed the House?

 I don't think so. I really do think that a lot of this is coming from unfounded financial concerns, we've seen this from a couple of states that are asking for some flexibility in terms of how much they pay for these medications.

But again, as you look at the data on this, it really is not a driving concern for Medicaid budgets. So I think that, sure, I think it makes some sense to look at the timeline of some of the confirmatory trials post approval. Hopefully, just continue to give flexibility to the FDA to say, well, we really don't need to do this, and here's the reason why. But that's really the major thrust of what the House has passed.

 What are the arguments in support of the continuation of the FDA’s accelerated approval pathway, and do you think that these arguments might be paid a bit more attention in the Senate?

 I hope so. The main benefit is that it saves time and lives, instead of waiting years for an experimental drug to show a primary clinical endpoint, like prolonging the life of a cancer patient. In a clinical trial, this process allows the use of surrogate endpoints like shrinking a tumor, which are associated with extended life, and to get those new treatments to patients faster. Like I said, something on the order of 3 to 3 and a half years faster than otherwise would happen. So I think it's an incredibly important tool for treating patients that have cancer and rare diseases, and as we've seen it has been critically important in the HIV/AIDS world.

 How could this legislation impact the future of drug approvals?

 Again, I don't know that it's going to have a huge impact. Again, as I've mentioned, it's just providing some additional structure on the timing of when the manufacturers have to do the post-approval confirmatory, more traditional studies, and it gives give some guidance in terms of when the study layout has to be outlined. You'd have to provide reports back to the FDA within 180 days post approval just on the progress of what's going on. So I don't think the process will change, it's just more this timing and structure of these confirmatory studies that that have to happen.

 Yeah, I just want to say hopefully that when it's finally done, we don't want to create any uncertainty about drugs’ likely approval; this program has been incredibly successful in getting treatments to patients.

I understand the rationale for putting some more structure on the timing of confirmatory studies, and hopefully, the flexibility the FDA would retain and not requiring them, but we just certainly wouldn't want to raise concern or doubts about a drugs’ likely approval because it really has been such an important program for large number of patients that otherwise may not have other treatment options.

Ken Thorpe, PhD, professor of public health at Emory University and chairman of Partnership to Fight Chronic Disease, discusses legislation that the US House of Representatives recently passed to put greater restrictions on the FDA’s accelerated approval pathway.

Implications of Legislation Passed in the House That Places Restrictions on FDA Accelerated Approval Pathway for Cancer, Rare Disease Drug Pipeline

 interviewed Zahra Mahmoudjafari, PharmD, BCOP, DPLA; Alison Gulbis, PharmD, BCOP; and Kamakshi Rao, PharmD, BCOP, FASHP, on a 2022 ATOPP Summit session they will be co-presenting in addressing research they conducted assessing the underlying causes of the hematology-oncology pharmacist great migration.

 What is the hematology-oncology pharmacist great migration, and when did it start?

 That's a great question. Honestly, I couldn't put a finger on when it exactly started. I think we all began understanding and recognizing it about a year ago when we met for a brief conference in June of 2021 and recognized that a lot of our colleagues and team members who have worked with us and alongside us in direct patient care roles, since transitioning to different roles, were doing different things.

This allowed us to start questioning why this was occurring and led us to ask those questions directly to our colleagues, and we got together at the end of that conference, and at the time phrased it, as “the great migration. There are other publications that are available for the general workforce, specifically looking at what is called the “great resignation.” But we chose to call it the “great migration” because our pharmacists are still working in the field of pharmacy in some capacity, just not necessarily in direct patient care role. So we were motivated to figure out why some of those reasons were occurring to motivate our team members to move on to non-direct patient facing roles.

 I think I would only add to it to say that I think pharmacists have been migrating amongst clinical and other roles for a long time. So it's not new to have pharmacists moving around or changing roles. I think what we had talked about was, I think it was 2 things.

The first was the rate of change, like how quickly it seemed like every few days, every week, we were hearing about somebody who we were quite familiar with, and I think the 3 of us are pretty well connected at knowing oncology pharmacists throughout the country, and so it sort of startled us to see the pace of change.

Then, I think, there were probably for each of us a couple people that we knew that in our heads, you just never would have thought that would happen. They were someone who, when you met them, you're like, this is a person who is going to be in patient care for the duration, it's completely their zone. Then to watch those people making decisions to leave patient care—I think those 2 factors sort of piqued our ears as to something different is going on here, something has changed.

 How did the pandemic contribute to this migration?

 Yeah, I think the pandemic maybe hastened what was already occurring and made it potentially even more painfully obvious, thinking it was a time where pharmacists really had to sit down and evaluate what mattered to them. So sometimes, what mattered to them was increased flexibility and their ability to work from home. What was what mattered in terms of their own mental health or career advancement—they took some time to really evaluate that specifically, and I think it just escalated it and really highlighted it and just really wiped the rug out from under us.

So I think it has really made me look at it in a more positive light and enabled us to really look at some of the things that are the root of the issue and allow us to have a lot more honest conversations. So, therefore, our patient-facing pharmacists can really have the time to spend with our patients and to take care of our patients, and we have more honest conversations now than we've ever had before. So I kind of like to think of it as a positive. But certainly it has been a tough couple of years, and I think for all of us in so many ways, just as you thought you got over one thing, the next problem came along.

Certainly what other facet of this is direct shortages that never went away, and it's only getting worse, it feels like, by the end. So again, I think the pandemic helped highlight it, but also helps us understand some of these core factors and core reasons it was already occurring, it just maybe hastened it.

 I think to add to what Zahra said about the whole work from home thing and flexibility that people realized was out there—a lot of institutions took these clinical pharmacy specialists who had direct patient facing roles and made them work from home. So it really started a realization that the flexibility is helpful for some, but, on the other hand, I think work from home also blurred the lines of when you stop working. Also, I think that made people reflect on their own personal time and what they needed, so I think that has been a contributor as well.

What are the causes of the great migration, and is it primarily burnout?

 Burnout is a big facet, but it is not the only reason. In fact, our research found a lot of emerging trends, some of which were more obvious than others. Some of them are kind of surprising things that we would call low-hanging fruit that institutions can implement pretty quickly to try to help retain staff.

One thing that came out pretty loud and clear was the team members want more support, and potentially better patient ratios. They're feeling lack of recognition, they're not feeling valued, necessarily.

One thing that came in loud and clear was just the number of administrative responsibilities that our pharmacists have taken on both in the military spending as well as a QA person. Another facet was flexibility in wanting to work from home potentially, and then there's other facets, including career advancement—I think our pharmacists are extremely high achievers, and they want to continue to work towards something. Some of them have different strengths that don't necessarily mean that they want to be in direct patient care, providing avenues for them to explore those opportunities are all facets of some of the trends that we identified in our research.

Again, there's some other, like I said, low hanging fruit, those include things like board certification support, the ability to attend conferences, and to network with other colleagues, which we consider to be something that could be easily achievable, if given the right resources, but it's not simply just burnout.

 I would have to call attention to, I think, burnout and wellbeing are very important. And you consider that so many things intersect and contribute to someone's risk of burnout and wellbeing. Those things can include more than just workload. We did hear about from a lot of people who felt like their desires for advancement didn't fit the strict narrative of the position descriptions that they had, feeling like their time was being nickeled and dimed to things that really weren't utilizing their skillset, so when a pharmacist is spending inordinate amounts of their days on insurance authorizations on trying to navigate the system versus being able to actually provide care to patients.

We also heard from pharmacists within oncology that are also involved in so many different things—teaching, research, committee work, representation and service on local, regional, and national organizations, and most of them are doing that on their own time.

Also, just tying back to the discussion around the pandemic, our own time became more important than ever. So when things started to creep in, and the idea was all the achievement you want has to happen on your own time. It really changed people's level of satisfaction with how their professional advancement was not tied to the appropriate metrics. So I think we heard a very loud call for more appropriate metrics that drive clinical pharmacy practice and career ladders and advancement opportunities that are more than just pharmacy administration as 3 individuals who have made those transitions into administrative roles. I think 3 of us have had some really healthy discussions about how that was the only option for advancement, and we pursued those options. But if we could turn back the clock and consider advancement using different avenues, whether it was getting protected time for education research scholarship, that would have changed the course of many pharmacists who have chosen admin as a path that may have changed the choices they made.

Zahra Mahmoudjafari, PharmD, BCOP, DPLA; Alison Gulbis, PharmD, BCOP; and Kamakshi Rao, PharmD, BCOP, FASHP, discuss the underlying causes of the hematology-oncology pharmacist great migration from the field.

Experts: The Hematology-Oncology Pharmacist Great Migration Is Caused by Issues Outside of Burnout That Could Be Quickly Addressed

 When we think about BTK [Bruton tyrosine kinase] inhibitors as a whole, there are some clinical pearls and takeaways. As a pharmacist who leads an entire pharmacy department, I usually think of some drug interactions that we constantly need to be looking at. If a patient might be on a gastric-reducing therapy, how is that going to interact? If a patient has a fungal infection and is on an azole, how is that going to interact with BTK inhibitors? When we focus on those, what are some key pearls that you have for our viewers in terms of efficacy, resistance, intolerance, or any type of dosing or adherence that you’ve seen from your real-world practice?

 That’s very important, because many of these cardiac arrhythmia drugs that many older patients take—like amiodarone, and anticoagulation, like warfarin or omeprazole—are the common drugs that patients use when you look at their medication history. These drugs can influence the adverse events and increase the levels of BTK inhibitors in the blood, which can increase the risk of toxicity, so we avoid the concurrent administration of these drugs with BTK inhibitors, most commonly ibrutinib. With acalabrutinib and zanubrutinib, we’re noticing that these patients can also have interactions, so we change the medication to an alternative H2-blocker agent. This problem isn’t as common with pirtobrutinib because there aren’t any data that pirtobrutinib, the newer BTK inhibitor, can influence that. But we do that stratification.

The second thing is about the antifungal agents, which is very important: azoles vs nonazoles. With the azole group, if the patient is taking posaconazole or fluconazole with these, then we have to change it to isoconazole or space out the duration of administration about 6 hours after taking the antifungal medication. Those are the some of the adjustments we make.

There are some specific things to pay attention to. If a patient already has a history of atrial fibrillation or paroxysmal atrial fibrillation, we avoid ibrutinib. If a patient is young and has a history of migraine, acalabrutinib is the only BTK inhibitor that’s associated with headache. We’ll be very careful with a young patient with a history of migraine.

With covalent BTK inhibitors, before, some of the patients with mantle cell lymphoma would have lymphoma cells in the peripheral blood. If you give them covalent BTK inhibitors, they’d have phenomena where the lymphocytosis will increase before it decreases. Sometimes we have to be aware of the blood viscosity and the risk for DVT [deep vein thrombosis] and tumor lysis. Pirtobrutinib doesn’t have this. But pirtobrutinib is still an early drug with few years of follow-up time, so we’ll continue to pay attention to the adverse effect profile along with more people treated with longer follow-up time.

 When we think about adverse effects and treatments, 1 thing I like is leveraging real-world evidence. Ibrutinib and some of these have been on the market a little longer. There has been higher utilization in the past, but these next-generation BTK inhibitors offer a lot of advantages for patients. We’ve gone through those. We don’t need to rehash too much.

Dr Jain, you and Dr Constantine Tam and others are bringing a lot of literature to the forefront as clinicians are trying to decide. When I interact with providers who might be in the community setting or might be more familiar with some of the first-generation BTK inhibitors, there are some differences between the next generation and the first generation. Some of that has to do with the pharmacokinetics that we think about quite often. Sometimes it’s the drug-drug interactions of statins and zanubrutinib. Or its the ease of use, whether a patient has to take it with or without food. When you want to break this down to people who are helping influence treatment decisions or management, what are some of the key differences that you’d like to call out between the first- and next-generation BTK inhibitors?

 Those are very important and practical questions that patients ask on a day-to-day basis. As Dr Wang mentioned, you have to look at the particular BTK inhibitor to see whether it’s going to be suitable for a patient. For example, when a patient has a significant history of cardiac issues or cardiac arrhythmias, we’d be very careful about giving ibrutinib by discussing it with the cardiologist. We’d look into administration of acalabrutinib or zanubrutinib for those patients.

If a patient has a previous history of migraine, as Dr Wang suggested, then because the most common adverse effect of acalabrutinib is headache, we’d clearly stratify and discuss this with the patient and observe and monitor. If the patient has a GI [gastrointestinal] history, diabetic history, or a history of diarrhea or some other GI malabsorption syndrome, we’d look to avoid zanubrutinib because that more commonly has a tendency to cause GI upset. If a patient has a bleeding or coagulation tendency, a protein C or protein S deficiency, or they’re already on multiple anticoagulants, then with all 3, we’d look at the risk and benefit or dose reduce or change to a direct-acting oral anticoagulant or space out the administration of the drug.

The second-generation BTK inhibitors have a much more favorable profile compared with ibrutinib. The incidence of major bleeding is also being reported with ibrutinib. If the patient is on azoles or has a previous long-term administration of ibrutinib, that’s also reported to induce the risk of CNS [central nervous system] aspergillosis or high risk of aspergillosis, but it isn’t as reported with acalabrutinib and zanubrutinib. In that situation, if your patient has a previous history of recurrent fungal infection, you’d lean more toward the next-generation BTK inhibitors.

Ryan, as a PharmD and a leader in the field, you can give an even better profile on BTK inhibitors, their drug problems, and so forth.

 I agree with what Dr Jain said. You have to be patient specific. Is the patient on corticosteroids? Could they potentially have had a fungal infection in the past? Is that something I need to consider when treating with this medication? I like looking at the pathophysiology and thinking about the cardiac history and how that’s going to come into play with these patients. Typically, is that something I need to be concerned about? If it is, I need to [adjust the] dose or select our therapy appropriately on the front end. At the same time, if any therapies can be modified, I want to do that as part of that patient’s plan and reach out to that primary care provider who started that therapy.

Those are some of the unique things I consider when it comes to adverse effects. When there’s mechanism of action, I also want to think about what the resistance is going to be like with these BTK inhibitors and how mutations come into play. That’s the next step as we’re selecting therapy. Third, agnostic of all the clinical criteria, which are extremely important, I want to make sure our patient is going to adhere to the therapy. If there are any cytochrome P450s or inducers that patient is on, I want to be very thoughtful about that to make sure that I’ll get them on the right therapy and they’ll be able to maintain that therapy through that duration of therapy.

Many times, the frustration for me as a PharmD and someone who’s treating patients is when a patient abandons therapy too soon, or for some reason has any rate-limiting adverse effects and we haven’t done anything to dose modify that patient or at least intervene early on. That’s where I feel my role or the pharmacists’ roles comes into play—team-based care, where we’re complementing the great therapeutic decisions that you and Dr Jain are making and we’re helping make it patient specific. We’re educating them. We’re anticipating any changes in therapy or adverse effects and providing early intervention.

Drs Haumschild, Jain, and Wang discuss clinical pearls regarding BTK inhibitors, including drug interactions.

Optimizing The Impact of BTK Inhibitors 

 interviewed Andre Harvin, PharmD, MS, executive director of Pharmacy, Oncology Services at Cone Health, on an ATOPP session he will be moderating that addresses ways of developing greater workforce diversity in cancer care.

At the ATOPP summit, you will be moderating a session on developing greater workforce diversity in cancer care. What are your views on methods of accomplishing greater workforce diversity in the field?

 Yeah, so well, my hope is that our panel will help us answer this question more so than anything else. But from my perspective, it really starts from a much younger age than when you're already a pharmacist and you're deciding what to do. We know that there's compelling data that shows that if patients don't see themselves, which means that their providers don't reflect them in their community, then there are poor outcomes associated with that. We see that especially in aspects like breast cancer, that there is a very distinct divide in terms of outcomes with Black women compared to their non-African American counterparts, and why is that? A lot of times, it's just, there's not that familiarity. There's not that overall trust that's there, and we have to find ways to bridge that gap.

We know, and I can say, I can attest myself, a lot of times, I'm the only person that looks like me in the room when we're talking about aspects within oncology or oncology pharmacy specifically, and that's not something I want to occur. I want our entire population to be represented in those conversations. We need to make sure that our pipeline of pharmacists that are coming out, starting to fill those needs throughout the country of where do we see these populations of African Americans, Hispanic Americans, or Asian Americans that need greater representation, that need to be brought to the table, and make sure that we have a compelling workforce that reflects that. So it's something that's going to take us time.

I think what we're going to see right now is that the data shows us that really within pharmacy as a profession, and then specifically oncology pharmacy, the diversity is lacking. And that's okay, as long as we can acknowledge it as a profession and as a subspecialty within that profession, and then ask questions like we're asking now, 

It's going to start at a much earlier phase, we have to make sure that we're touching these children at the high school and middle school level and making sure they have interest in pharmacy is profession making sure they understand that oncology is a subspecialty that they can go into that can be really successful for them, and that needs them at the table to help represent that population that they can serve one day.

What are some challenges you see ahead when working towards the goal of creating greater workforce diversity?

 There's a lot of challenges when it comes to creating greater workforce diversity. One of the more pivotal ones is really getting people to understand that it's a problem. When we talk about things like diversity, equity, and inclusion, we would be ignorant if we said that there was not ingrained pushback against that within our country, and we have seen that play out over the last several years. They sometimes say that's part of woke culture like it's a negative, and really, what I tell people is like, let's get away from the emotional aspect of talking about diversity, equity, and inclusion, and just look at the data. The data really show that when it comes to disease burden, health outcomes, access—there are very clear lines that occur between African Americans, Hispanic Americans, Native Americans, and some of their White counterparts. There are just inefficiencies. There are failures there at a systemic level.

We are here as caregivers, right? We got into this profession as pharmacists, as physicians, nurses, whatever have you, because we wanted to help people. None of us got into it because we wanted to just help Black people or White people or Hispanic people or Native American people—we just wanted to help people, and we have to recognize that to a degree we fail some of those subsections of our American population.

So probably one of the biggest challenges is being able to recognize our failures and accept our failures, and then say, how do we move forward as a profession and as an industry in health care to help reduce some of those failures and reduce some of those gaps that exist in care today, and that takes all of us. It's not just saying that what would need to occur is we need more Black pharmacists that are interested in oncology, we do need that. But we also need the support of our White counterparts and our Asian American counterparts to support us and help uplift us and introduce us to those opportunities when they see fit. So we all have to come together as a profession as experts to say that we want to be inclusive as a profession, that we want to be inclusive in terms of those of us who help lift this disease burden that is oncology, and that it's important to all of us.

Probably number 2, the biggest thing is we all need resources. So right now, as we've got issues within the economy, there's a lot have worries around recession, people are worried about how they're going to fill their tanks up with gas, saying, ‘

Hey, we have to focus on putting effort and FTE and capital dollars towards building more diversity and a more equitable society.’

 Again, some people are going to initially push back on that. But again, the data show that when we embrace things like diversity, equity, and inclusion, it makes us better, and helps us bring new resources to the table that help us bring new ideas and solutions to the table that we couldn't if we only play in a very small box.

So, not only is it critical when we look across the country that we have to bridge these divides, but it's critical when we look at the disease that is cancer that we are better together. That's what this is about. It's like how do we ensure that the people that we care for they can see themselves and the people that care for them?

What could be the impact of bringing greater workforce diversity into cancer care in terms of patient care and outcomes?

 The impact of diversity, I think, is going to be very clear. I know one of the biggest aspects that we talk a lot about is not necessarily what we're going to focus on a lot in this forum, but I feel like the conversations are going to go there, especially before and afterwards, is when we think about clinical trials. Clinical trials are a huge area, it's a huge opportunity, but we continue to see the disparities there, when we look at well, in what population was a new drug, or this new therapy, tested.

Right now, we just don't get a lot of participation from African Americans, Hispanic Americans, and Native Americans in these clinical trials, which means that if there are differences, if there are reasons that an African American should receive different doses, or they need to be adjusted, which is going to be different from their Caucasian counterpart, we're not going to know that because we're not getting enough of that diversity at that clinical phase trial. So the hope is that we find opportunities to really get past the mistrust that certain demographics have with public health care, and we have to understand that that's there for a reason, because there's history around that, there's reasons for certain populations not necessarily trusting when it comes to like clinical studies or drugs that have been FDA approved. So we have to find ways to bridge those gaps.

I think what's going to be most important, though, is when we look at the outcomes. I constantly look to it is that when we looked at breast cancer survival rates, and the impact that breast cancer has within populations in the United States. African American women are at the very rear of every single measure you can look at. They're more likely to become food insecure, they're more likely to become shelter insecure, they're more likely to have worse outcomes and more likely to deal with additional comorbidities during their cancer care, and there really isn't a reason for it. The reason is because we have unconscious biases that find their ways into clinical decisions. There is an overall, again, mistrust that sometimes still occurs, but we can combat that. So, my hope is that we really focus on some of those areas where we know we can bridge those divides, we know we need to get more diversity in clinical trials, we also know that we have very specific disease states where we have drugs that can improve patient's outcomes, we have to make sure that they're being prescribed to them accurately, and that they have the same access to those drugs that they're maybe not African American counterparts have. So there's a lot of downstream outcomes that can occur.

I'm very hopeful that when we look at breast cancer 5 to 10 years from now, we start to see an erosion of those differences between Black women and White women. But that's going to take all of us coming together and all of us focusing in recognizing that it's a problem.

 So what I'm hoping that everyone comes away from this session, when we talk about building a more diverse and equitable workforce, is that we are all so much stronger when we come together. The really great thing that I love about not only ATOPP, not only the profession of pharmacy, and that subspecialty that is oncology, is that it is a small world. I mean, we know each other when we go to these meetings, we've seen one another before. We’ve spoken to them in different conferences, we put messages on ad boards to ask them like, 

‘Hey, where are you doing in this situation? What are you doing in that situation?’

When we all come together, I think we can certainly recognize that we still have areas of improvement, and we can rely on the data to show us where we need to improve, and that's what we hope comes out of this session is that there is a lot of emotion around it. There is sometimes it's going to make us feel and potentially squirm in our seats to hear that as a profession, we still have a problem, we have divisions when it comes into race and gender that we need to work on. But the great thing is that, again, we all know each other, we all know why we're here, and why we came into this profession and the subspecialty. Because we want to end the burden of cancer.

When we say that we have to do that, across the board, we never came in as to say we want to end the burden cancer in these specific patients, or patients that look like me or don't look like me, we want to end the burden of cancer really across the world. I believe this group can do that, by helping understand that we do that by ensuring that we have an inclusive workforce. That's going to take time, it's going to take commitment, it's not something that we fix in the next couple of years. It's something that we have to fix over the next 5, 10, 15, 20 years is that we have to continue finding opportunities to help ensure that we have a diverse workforce. So my hope is that this is step one, which is having that conversation, articulating and recognizing the issue, but also understanding that the person next to us is not the problem. They're going to be who we look to in terms of solutions. So I hope that everyone looks at themselves in the mirror after they leave and say, 

‘What is my role in helping build a more diverse workforce?’

 If we can do that, then we have succeeded.

Andre Harvin, PharmD, MS, executive director of Pharmacy, Oncology Services at Cone Health, discusses methods of accomplishing greater workforce diversity in the field of oncology pharmacy.

How to Bring Greater Workforce Diversity to Oncology Pharmacy

 We talked about the concept of a chemotherapy-free regimen. Looking into the future, how can we provide therapies that provide a good quality of life and are less toxic, so patients can handle? That’s the exciting piece of clinical trials, but also leveraging innovative mechanisms of action in combining these targeted therapies. In that vein, I’d like us to talk about BTK [Bruton tyrosine kinase] inhibitors, because that’s an innovative area. When we think about BTK inhibitors, we obviously think about ibrutinib. It’s been around. There are a lot of clinical data there. There’s also acalabrutinib and zanubrutinib. We’re thinking about some of these first-generation and next-generation BTK inhibitors. Dr Jain, can you explain the differences and similarities of BTK inhibitors as a whole and how they play into the pathophysiology of mantle cell lymphoma?

 This question can be answered in different ways, but BTK is a protein. It’s a large protein with almost 700 amino acids. This protein is called a Bruton tyrosine kinase. It’s like other cancers, where there’s a signal transduction pathway. It’s 1 of the important tyrosine kinases in the cells of mantle cell lymphoma, which is shown to have a very significant role in signaling the cell growth proliferation and survival.

The B-cell receptor is basically a receptor complex that has different subunits. Whenever there’s any antigen that’s promoting the signaling, it goes via the BTK. We’ve seen that if you block this enzyme, the intracellular signaling pathways are abrogated. Once they’re abrogated, the downstream propagation of these into the transcription factors is gone. Once that’s done, then the cell division growth proliferation—everything is affected. That’s how the BTK inhibitors were developed. Canine lymphoma models were the first, where Dr [Lee] Honigberg reported those.

Because the BTK enzyme is big, it can [resemble] some of the other enzymes present in our body, such as in the heart, pancreas, lymphocytes, and other areas and immune cells. When ibrutinib was discovered, it was identified to be blocking this big enzyme. But we were noticing some of the adverse effects from ibrutinib therapy over the long term. Then they went into developing more specific drugs, such as acalabrutinib and zanubrutinib, which are more selective and with fewer off-target effects. These 3 are the covalent innovators. That means they bind to the BTK protein and particular domains in a covalent manner. But whenever the BTK enzyme is recovered, these drugs become resistant. Although you have fewer adverse effects, the question comes about resistance. That’s why new BTK inhibitors, such as pirtobrutinib, have come into picture.

Dr Wang has led the major study on the pirtobrutinib, which is a major advancement in mantle cell lymphoma. They’re also reversible. In spite of a higher turnover rate, they can keep blocking by hydrogen bonds instead of the covalent bonds. That makes it quite unique and very well tolerated. This way, you develop the BTK inhibitors again into first generation, second generation, and now the new generation and third generation of agents. This is how it pans out.

 In the past, patients came to our clinic and said, “Dr Wang, I don’t care what you do. Just get rid of my lymphoma.” These days, things have changed. The young people come here and say, “Dr Wang, I want you to get rid of my lymphoma without using chemotherapy.” All this therapy described by Dr Jain, with BTK inhibitors, covalent, and reversible, together with the other agents shall be combined as chemotherapy-free therapies to gradually replace chemotherapy so that we can reduce acute toxicity and the longer-term toxicities, such as secondary and primary malignancies, which will be a bigger problem in the future. We’re not only using chemotherapy-free therapies, we’re adding immunotherapies and CAR [chimeric antigen receptor] T-cell therapies. Our field has never been so exciting. Dr Jain and I work hard, but we’re also working hard with excitement.

 Your passion for patient care comes through on this video. That’s what I wanted people to see: that innovation and great knowledge. You’ve explained how far we’ve come and how much further we want to take the therapeutic choices that are still out there. Dr Jain, you did a great job describing some of these BTK inhibitors. We’ll get back to some of the pathophysiology about the off-target effects on the heart, because that’s going to come into play as we talk about some of the management. But talk me through how BTK inhibitors changed the therapy and outcomes for patients with mantle cell lymphoma.

 Recently, a Connecticut group from Yale [University] did a fantastic job of looking into patients who’ve been treated with BTK inhibitors across the United States. More than 3000 patients were reviewed, and they divided these patients between 2012 onward and prior to 2012, patients who haven’t gotten a BTK inhibitor—pre-BTK era—and those in the post-BTK era. Those patients were subdivided into different age groups. Clearly, there was an overall survival impact by using BTK inhibitors in patients between the ages of 70 and 80 years, with patients at least 65 years and older and up to 75 or 80 years old. In the multivariate analysis, this age group best benefited from improvement in the overall survival. That’s the major advancement in mantle cell lymphoma.

 Dr Jain, as we think about these innovative products, are there patients who aren’t eligible for BTK inhibitors? How would you identify a patient like that during the course of therapy?

 That’s a clinical scenario where we see that these patients are already having a very bad cardiac condition with advanced cardiac comorbidities. Clearly, we have to choose the BTK inhibitors very carefully for these patients because of the risk of cardiac arrhythmias or different patterns of cardiac arrhythmias, not only atrial fibrillation. There’s a different spectrum of cardiac arrhythmias described with the use of ibrutinib and the other BTK inhibitors. Compared with ibrutinib, the incidence of these adverse events is much less with the newer BTK inhibitors, such as acalabrutinib and zanubrutinib. But clearly, they’re also able to induce those adverse effects.

If the patients have those conditions, then we have to carefully discuss with the patient and get cardiologists to see these patients, get the loop event recorder, maybe get the abolition, and then carefully assess with the patient the need for anticoagulation, because bleeding tendency can also get worse. There’s an interaction of BTK inhibitors with the warfarin type of agent, so you have to look at direct-acting oral anticoagulants. These are the things that you have to carefully discuss with the patient in conjunction with the cardiology consultation. That’s a major comorbidity that you’d discuss.

The second comorbidity you’d discuss is hypertension. With long-term follow-up, ibrutinib-associated hypertension is an important thing that has come into the picture. You discuss optimal management of blood pressure with these patients. Those are the 2 common clinical scenarios. There’s bleeding tendency, as I mentioned, which can be also induced with acalabrutinib and zanubrutinib, but it’s more like superficial bleeding. Clearly, you have to weigh the cardio and vascular comorbidities together.

 That was a great overview of those unique patients and what we should be on the lookout for. Not only who’s ineligible but what to monitor. I like how you touched on hypertension and tied it back to that pathophysiology.

This panel of experts navigates the effects of BTK inhibitors, and their impact on trpatients with Mantle Cell Lymphoma.

Utilizing BTK Inhibitors to Achieve Chemo-Free Therapy

 spoke with Paul Feuerstadt, MD, FACG, AGAF, about the investigative 

 treatment RBX2660. Recent research investigated its efficacy in patients with underlying comorbidities.

Q: What underlying comorbidities can affect patients with C. diff?

So, there's a lot of comorbidities that can impact patients with C. diff. Really what you're asking me is what are the risk factors for recurrence, and I like to group these into several different categories: demographics, medication, exposures, environment, and bacterial virulence factors. From a demographical standpoint, age over 65, any form of immune compromise (chronic kidney disease, HIV, inflammatory bowel disease, diabetes), any distant history of 

 can play a role. Medication wise, antimicrobials are a big player, amoxicillin, ampicillin, clarithromycin, fluoroquinolones, cephalosporins, piperacillin tazobactam. As a gastroenterologist, I of course have to include proton pump inhibitors, because they always show up as a risk factor for initial infection and your risk factor for recurrence. We believe it's actually a result of alterations to the microbiota. When we think about bacterial virulence factors, we think about the NAP1/B1/027 strain or the hypervirulent strains, as well as whether the patients have severe infection defined by a white cell count greater than 15,000 and creatinine greater than 1.5 milligrams per deciliter. And finally, the environment that the patient is coming from, do they live in a skilled nursing facility? Are they in the hospital frequently, because if they are, they probably have a lot of the other risk factors. But also, they're surrounded by people who potentially have 

So, when we contextualize this information, it's important to understand who's at greatest risk for recurrence. And what this abstract did was it looked at something called the Charlson Comorbidity Score, which is a scoring system for underlying comorbidities. And within this study, patients were grouped into 1 of 3 groups: mild Charlson comorbidity score, which is a score of 0 to 2; moderate score of 3 to 4; and severe, greater than 5. And using this breakdown, we carved up the specific PUNCH CD3 cohort of 262 total patients, and 107 of them had mild disease, 71 had moderate, and 84 had severe. And then we looked at the efficacy of RBX2660 within those subgroups, different than the subgroups from the other abstract.

And what they found was very consistent efficacy. Efficacy was 76.5% in the mild group, efficacy was 68.0% in the moderate, and 67.8% in the severe. So, we see trends for greater efficacy than placebo in all 3 groups. Importantly, in the mild group, as you would expect, as a younger group, you have a greater efficacy at 8 weeks than the moderate and severe. Interestingly enough, there were very similar treatment effects—68.0, 67.8%. That is despite the placebo effect, the placebo treatment being lower efficacy in the severe cohort than the moderate cohort. So, what we're seeing is RBX2660 really being consistently efficacious, but having a very profound effect in the moderate and severe cohort, again, speaking to the fact that this is a product that can be used after standard of care antimicrobial in a broad range of patients and still have very good effects.

Are there gaps in care for these patients?

So, without RBX2660, they're facing being treated only partially, right? As we discussed, RBX2660 as a supplement to the microbiota, what we're currently using are antimicrobials. And then if you have the opportunity to go to a coronary care center where fecal microbiota transplantation is performed under enforcement discretion through the FDA, you might be able to get that second piece to shut down the cycle of recurrence, but the majority of patients don't have access to that. Thus, they're really only being treated with the standard of care antimicrobials, and it's up to their own microbiota to regrow and that leaves these patients prone to that 35% initial recurrence rate. And up to 65% of those with 2 or more recurrences getting stuck in the cycle of recurrence after recurrence after occurrence.

Q: Can you discuss the safety profile and adverse effects for RBX2660?

You know, that's a really important question. Safety signals with regards to RBX2660 have been on par with what one might expect and they're really minor. The majority of patients that have side effects from this are usually gas, bloating, or changes in bowel habits. They're usually short lived, and they're classified as minor. Lindy Banky presented a very nice abstracted at ID Week back in the Fall of 2021 that looked at the 3 phase 2 trials and the 2 phase 3 trials considering RBX2660, and showed very consistent safety for these products and in a separate abstract consistent efficacy. So, we see that the safety profile for RBX2660 is very encouraging as well.

You know, I think I'm just going to add something in general. You know the Charlson comorbidity poste, and the subgroup analysis shows broad applicability of this product. The recurrence data shows again broad applicability of this product consistent with what many hypothesize with microbiota-based live biotherapeutics. I think it's just so important to understand that RBX2660 and microbiota-based live biotherapeutics are the future, they are going to be a piece of how we treat 

 infection. And we're really seeing the light at the end of the tunnel. We're seeing, hopefully, an FDA-approved product within the next 12 months. And if that happens, this will give so much better access to so many more patients of treatments that they need to shut down that cycle to decrease morbidity, to decrease mortality, to improve patients’ quality of life. So, as a clinician, it's just so exciting for me to see the potential for broad applicability of technology that I've had access to for a long time with foundational fecal microbiota transplants. But now, having phase 2, phase 3 data that's consistent in a broad range of patients, that's incredibly exciting for patients and for clinicians.

Pharmacy Times spoke with Paul Feuerstadt, MD, FACG, AGAF, about the investigative C. difficile treatment RBX2660. 

Investigative C. Diff Treatment Shows Success in Patients With Underlying Comorbidities

 interviewed Bhavesh Shah, RPh, BCOP, steering committee co-chair of the 2022 Advanced Topics for Oncology Pharmacy Professionals (ATOPP) Summit, on what ATOPP is as an organization and highlights of the upcoming ATOPP annual summit in San Diego, California taking place from July 14 to July 16, 2022.

Could you tell me a bit about how the ATOPP summit impacts the oncology pharmacy field and about your work on the ATOPP steering committee?

 I feel like more and more people are asking, 

because it's a new organization, and how to get involved with it and should they get involved with it. So, on the website, we actually develop FAQs, where people can learn what ATOPP is, and the genesis of it. Really, I think that a lot of the confusion has always been is it a community focus, is it IDN focus, who is the audience for this. So, we didn't want to create a disparity where you have to go to so many different conference or educational events. There are institutions that do pediatric and adult, and it's kind of also separates those specialists who work in the same institution.

So, we thought that we have a lot of folks who are on our program planning committee too, with expertise in pediatrics, and it was definitely an unmet need. So we kind of added a lot of content in the conference for pediatrics. So, I think the way I explain it to somebody when they're asking about ATOPP is that it's designed for a lot of your seasoned oncology leaders or pharmacists across the country to elevate the level of interactions that you have.

So, there's different levels in oncology. You have your directors, your VPS, and then your managers, and then your specialists. So, essentially, having presence from all of those leaders, I think, helps develop more conversations that you can solve, a lot of times, where you have an issue that kind of is presented by a specialist, and essentially goes up to a manager, or it goes up to a director, maybe the VP afterwards, so it takes a significant amount of time to solve something, or even identify that there was a problem. But if you're actually talking at the leadership level, you're able to change things much faster.

So, we purposely actually made sure that the leaders were actually at the table so that this is what the whole reverse expo is. There is about 40 plus VPs and directors from major cancer centers, not just health systems, but community practices, too. So really kind of a broad leadership community coming to ATOPP and then having also industry interact with those leaders, they can also actually have a much meaningful conversation. If there's a contract that can benefit that institution, it should be presented to the right person, and sometimes that gap that a lot of times from both sides where industry doesn't have access to the right person, and then the director doesn't know that there's a contract. So we thought that it would be really beneficial to actually bring everybody together, where we can provide education and solve a lot of the issues at hand.

So, the focus of the steering committee has really been to help guide and lead a lot of the initiatives that we're working on and really have some oversight and guidance in having seasoned steering committee members who've actually also been part of previous organizations where there are founders, so they have a lot of experience and are able to guide the agenda, a lot of the interactions, and how do we actually make things better having visibility on how other organizations put together their agendas. It helps us with how we can do better. So, I think this steering committee really was helping to steer a lot of them.

For example, one of the things that we had identified was, many industry partners want to do product theaters, which are great, but the feedback that we've gotten from our audience was that that's not something that they would like to attend, and it was not well attended in our last meeting. So really, the steering committee to this task was to actually provide benefits for industry partners, and then also bring value to our attendees. If we're really designing a solution for leaders, and seasoned leaders in oncology, we want to do better than just provide them manufacturer labeling information.

So, we actually came up with a lot of programs, essentially, called coffee conversations called ‘Spill the Tea,’ where it's very casual conversations about complicated cases or specific topics in mind. So really kind of bringing a group of leaders together in oncology to talk about a specific disease, or a specific case, or so I think it brings value to the industry partners, where it may be actually something that they want feedback on, and they want to understand how the oncology community is actually grasping this disease or managing this these types of cases. So, really kind of bringing the folks together in terms of discussions more casual, which provides the attendees with the choice of which topics they want to attend.

So, it kind of also brings value where they could go to an ITP discussion, because we know, there is emerging treatments coming out for ITP. There are constantly changes in practice, because of COVID and emerging data, so it could definitely be engaging to learn about this in a casual format. So I think really, getting away from the product theatres, where you're not actually looking at the package insert information, and having to be on label for everything—that doesn't bring value because you already know all that information, as that's on the label. So, then being able to interact with other specialists and leaders in that disease to learn from them. So I think we thought having a very free style with various types of these events embedded into the conference will be really valuable, and the topics can be chosen by our industry partners, and then audience can attend, based on their needs, in education in those topics, or in those areas of expertise.

So I think really making it more appealing from an educational perspective, so I think that's a uniqueness that we have. Of course, I think every single lecture is worth going to, but if I was to highlight, I think—the steering committee was like, ‘

What is the major things that institutions are thinking about currently in what are top of the mind.’

Essentially so, one of the things that we identified was many institutions were trying to develop a hospital at home program, and we've never seen anybody present any information on hospital at home program at any conferences, and how to do that, and then what successful looks like, what's not successful, so we actually pulled together institutions that are currently doing it across the country, so one in the East Coast, one in Midwest, or maybe it's just East Coast, but really kind of pulling those institutions together to talk about where they are with their program, and what it took to develop that and share best practices. Then we also have CMS, who actually will answer a lot of questions that institutions may have, who are either considering it, or actually have gone through the process and have successfully done it, but there's issues with reimbursement or provide feedback to CMS that, 

 So really it’s going to be very well attended, very engaging from all the leaders who are have a program or considering it, you have actually CMS there and leaders talking about that.

So, of course, as I said, I think one of the biggest obviously choosing the keynote speaker. I think that's very important. It took a lot of thought into it I think we looked at, obviously, other organizations, and also feedback from our teams and our audience, that what's the biggest unmet need is health inequities in oncology. It is on the top of mind for every single institution, even manufacturers, how can we increase access to our drugs, how can we increase access to innovative clinical trials to patients with diversity and inclusion, and really, I think we searched high and low when identifying the right speaker for the keynote, and with the Arya, who's been in this space for a very long time, and she's done a lot of work, and we thought that it would be perfect to actually bring in somebody with a lot of background and experience in the space to really basically bring to light what can we do when having the leaders in the room, having industry partners in the room, in terms of closing the gap in health inequities in oncology.

So, really, I think, obviously, I can go on and on about all of the great sessions and how much thought we put into them in terms of choosing a lot of things that we have, but I think just highlighting those few are probably top of my mind. Then I think in terms of just in the field of oncology, it's ever evolving, I mean, there's so many things that you can do professionally in oncology. You can specialize in a specific disease. I mean I think we've seen more specialization from pharmacists where they're more focused specifically on GU, myeloma, or BMT. So really, there's so much evolvement professionally that oncology has.

Then I think, really, there's definitely been a shift of many of my colleagues. I mean, we saw Larry Buie, who was actually the president of HOPA went to BMS, a huge statement there. What is going on here with such a big shift, and I think that goes to, basically, the keynote that HOPA had in terms of pharmacy burnout. Industry is not this place where the grass is always green and this rosy picture. There are definitely a lot of challenges with industry that you have, but I think the more people are looking for that remote opportunity they're starting a family and the traveling and commute that they may have.

So not to mention, hospitals are very stressful, especially with COVID-19. I mean we've gone through so many different surges, and I think people are just burnt out. So I think there's burnout that actually eventually leads to kind of people thinking about, 

‘Hey, I'm going to try something different, this is my opportunity.’

 I mean, you're actually able to make changes professionally. And if you don't, if it doesn't work out, there's plenty of oncology pharmacy specialist jobs. I mean, I have 4 positions open right now. So I think there's a shortage, and that's in oncology on the health system side, so I think that there's definitely a concern from I mean, obviously, from our community that, if this continues, how do we actually—we just added another oncology resident to our pool, but I think more institutions will actually have to consider adding more residency spots in order to grow more oncology specialists professionally.

So I think there's definitely, I mean, in a positive way, I feel like having people who are more have experienced in patient care, being involved in the day to day in an organization or a health system can provide a lot of value to industry, essentially because it feels like there's always this missing part with how did they come up with this, where did they come up with this formulation, did they not talk to a pharmacist before they develop this, this type of service or product—so I think really, there's a benefit for industry in a way where they're also getting a lot of good talent that could help them with better positioning their products and better partnerships, better value that they would be able to create with that type of expertise. So I think, really, it's a good, but there's always going to be a bad that you have to consider one side is always going to imbalance the other right.

So, I think the other questions you think we talked about kind of where can our audience go for kind of understanding what a top is, and I think the exciting part is that we had our first meeting last year, second meeting this year, we've already confirmed our third meeting next year in New Orleans. So I think, it’s really exciting that we're actually already on our way to our third meeting and are in our audience continues to grow. I think we're definitely doing something right, where we have so much excitement around our conference, and then partnerships—I think those are the ways really if we didn't offer the value that we're able to provide, I think we wouldn't have all the partnerships that we have in terms of the sponsorships.

Then the uniqueness, I feel like is always, what helps kind of drive educational organizations like this are what is the uniqueness? There's continuing education that I can get from any anything, but is this relevant to my practice, is this what I'm going to take back, is this something that's going to fill a gap, and I think, as more oncology leaders kind of see this, I think that we're going to get that to continue to grow the membership and really kind of continue to evolve the scope of our organization where I think we already had it and we want to focus on making sure that we're not actually just doing one thing a year, and then that's it.

So we have a lot of ancillary events that we're doing on the side or before the next conference, so we have educational CEs that we put out, again, similar to what we're doing in understanding what are the unmet needs, so we're working on a precision medicine continuing education activity, which is essentially bringing together a pathologist, medical oncologist, a pharmacist and a payer together, and they're talking about how, of course, you have all these FDA-approved testing that you can do for biomarkers, but we saw last year at ASCO, that lung cancer, which has the most amount of biomarker testing done, but 50% of patients are actually not getting all the tests that they should be, even though there's FDA approved treatments, not all the patients are getting that. Then if you look at African Americans, it's actually even lower. So really, we wanted to kind of bring together is this a payer issue, a provider issue, a pathology issue—are the pathologists falling asleep? So really, kind of talking through a lot of the inefficiencies that could lead to this, and how can we, by having these discussions, be stimulated to actually go back to practice and say, 

‘Hey, why don't I actually have a connection with my pathologist and my molecular pathologist and my interventional radiologist, and my medical oncologist, and why isn't the pharmacy involved in helping to support this.’

 We're just basically on the back end where, 

‘Hey, this patient has the EGFR mutation, they can have this medication, right?’

 Pharmacy is not involved in this train of thought, where until there is an actual mutation, and then a prescription.

So, I think really, what we developed at our institution is actually a weekly meeting that we have with our pathology and our medical oncology on various diseases, so kind of having an operational meeting to understand what do we need to fix not just for biomarkers, but all the broad molecular testing that we're doing her to PDL? One liquid, so, we want to make sure that we're actually supporting the providers, because when you have 40 plus providers across 50 different malignancies, and there's a lot of different testing that needs to happen. There needs to be constant communication because of the changes. I need, for example, SDK mutation, because it's going to tell me that a patient with PDL1 therapy, so they have a poor prognosis, and that's important to know. But that's emerging data the pathologist does not know, and the medical oncologist does not know if our NGS testing in house, we can do that, or if this is something that needs to go to external. So by having this collaboration and having this type of operational meeting, because a lot of folks actually have tumor boards, which are more clinical meetings.

So it's really kind of evolving to a more of an operational meeting to understand what are the inefficiencies that are causing this type of testing, because it's not just patients that don't have access to it, there is something in the system that's broken, where maybe the interventional radiologist doesn't know that this is a stage 4 lung cancer, and they're going to do NGS testing, and he needs to get as much tumor as possible. Because you can't do cytology, pathology, and the NGS testing with just one tumor sample, right. So I think it's like basically identifying all of those inefficiencies to close the gap in getting access, I don't think that you can solve this by just having the medical oncologist just try to do this on their own because there's so many other things going on. There is patient care, they're on-call, they are paged going in left and right. I mean, so having this structure, I think, can help overcome a lot of the barriers to access to precision medicine, which we know is driving oncology significantly. Then so I think really doing these types of important educational activities this is where like ATOPP really kind of comes together where it's not just clinical, and I'll also create another conference to go for your administrative knowledge that you need to gain, that there should be clinical and administrative together.

I think the other uniqueness about ATOPP is that we want to get more payers involved into our educational activities, because I feel like a lot of the problems that we see happening is because payers are not educated and in the differences and the change in data on how we function, so I think having more payers, we’ll probably have at least 2 or 3 payers this year, and I think that's going to broaden to much higher number of payers. So I think more and more, we're going to see more payers attending our conference and education and participate in our educational sessions.

I think one of the symposiums that we have is, there's a very simple symposium, it's IV iron. And you're like, what's so fascinating and about fascinating about IV iron and right, but we know that each institution is actually struggling with managing patients with IV iron, and because of the volume of patients that they have, there's no structure in terms of managing patients. There's a backlog and we know that if a patient doesn't get IV iron, they will actually end up getting a transfusion, or get admitted to the hospital, or actually miss their chemotherapy because they're too anemic to get treated.

Bhavesh Shah, RPh, BCOP, steering committee co-chair of the 2022 ATOPP Summit, discusses the impact of the annual ATOPP summit on the oncology pharmacy field.