Kirollos Hanna, PharmD, BCPS, BCOP

We talked about a lot of exciting things. Dr Perissinotti, why don’t you take us through what the role of the pharmacist is in the management of CLL [chronic lymphocytic leukemia]? We talked about treatment selection and strategies. But what can pharmacists do, or how can pharmacists become more involved in caring for these patients with CLL?

: Obviously, when you think of pharmacists, you think of our traditional role of ensuring that patients are adherent to therapy, that there are no drug interactions, there are no contraindications, that we’re selecting the right therapies based on comorbidities and whatnot. You certainly think about the pharmacist in helping with access, especially when it comes to combinations. When you’re now going to be adding 2 drugs, oral therapies that cost roughly $15,000 per month each, copay assistance is going to be incredibly hard. Getting funding for these—we’re going to run out of funding, so trying to develop strategic strategies to get patients’ therapy. Now, access, I don’t think a pharmacist should do. I think we should really advocate having support staff to be able to do this. That way, we can free up our pharmacists to really advance our practice. I think the biggest thing we really need to push ourselves to do is read the data. Read through all the literature. We went through so many studies, and this was just primarily study at ASH [American Society of Hematology 2021 Annual Meeting]. There are so many other studies out there. Keeping up with this is incredibly daunting and challenging. Just to read this information took us hours to prepare. Then you have to then apply these data to your patients, so that takes a tremendous amount of time also. And then you have to educate your physician colleagues and your nursing colleagues. I really think the role of the pharmacist should be critically appraising all this literature and identifying how we should be treating our patients in the clinical arena. And this is not only developing clinical pathways for the 80% of patients that this fits, but also for those individual patients that cookie-cutter medicine doesn’t work for so that we can think outside the box of what therapy is best for certain patients. I think those are some of the things that we should do as pharmacists. We should really push ourselves and really advance our profession by continuing to read, learn, and know everything there is about all the little nuances of the literature.

I couldn’t agree with you more, Dr Perissinotti. A couple of other things that I think would be very important for our pharmacists to consider, as you mentioned, drug-drug interactions. Those are key. Almost any patient that’s going to be treated with CLL therapy, 3A/3A4 inhibition; that’s going to be critical. BTK [Bruton tyrosine kinase], BCL2 [B-cell lymphoma 2], PI3K [phosphoinositide 3-kinase], really all the above. Another thing is infectious prophylaxis. So sometimes our pharmacists can have key interventions in terms of making sure that we make recommendations for certain patients that could be at high risk for developing infectious complications. We mentioned COVID-19 vaccinations earlier and what the implications there are, especially in those patients receiving anti-CD20 monoclonal antibodies. That’s going to be very important. Another thing, Dr Perissinotti, you had mentioned earlier is the absorption of these drugs. All our BTK inhibitors can be taken with or without food. But outside of acid suppression, etc, high-fat, high-calorie meals actually impact ibrutinib [Imbruvica] and acalabrutinib [Calquence] absorption. So those are also things that, although we can take with or without food, we have to be cognizant of and be aware of in terms of clinical practice. Some patients may require growth factor prophylaxis. Pharmacists can play a role in terms of developing pathways for institution; being part of that team, how you evaluate the data that Dr Perissinotti had just mentioned, again, outside of ASH; and incorporating that into your clinical practice and developing guidelines, your care model, your value-based care; and trying to move that needle forward. Whether it is indefinite treatment with BTK, finite treatment with BCL2 anti-CD20. Whether you break it down based on subsets of patients. All those are going to be critical strategies for your patients. And again, the amount of evolution that we’re seeing, that amount of combinations, sequencing the therapy is going to be very, very critical to success for these patients.

: Well, that was a really great discussion. I want to thank you Dr Hanna, for all of your comments. I was going to say, “Let’s open it up for more discussion to see what other unmet needs we have,” but we really talked about it all. I want to just thank the audience, everybody that’s viewing this, for your undivided attention. And I hope that you learned a thing or 2 from me and Dr Hanna. It’s been a pleasure. Hope that you found this 

Insight to be rich and informative. And with that, have a good evening.

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Drs Anthony Perissinotti and Kirollos Hanna provide some important considerations for pharmacists in treating chronic lymphocytic leukemia.

Chronic Lymphocytic Leukemia: Considerations for Pharmacists

Another exciting thing that we saw at ASH [American Society of Hematology 2021 Annual Meeting], CAR [chimeric antigen receptor] T in CLL [chronic lymphocytic leukemia]. Dr Perissinotti, what do you know about CAR-T cells?

: With CAR T, it has taken some time in CLL to come to fruition, mainly because we’ve had so many other good, effective therapies. And CAR T is expensive. It’s laborious. And there’s quite a bit of logistics for patients and toxicities. There were 2 abstracts at ASH that clinically aren’t going to change things but, at least scientifically, I think are really important. One was by Shadman [Mazyar Shadman, MD, MPH, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA] and colleagues. They were trying to show some responses in a third-generation CAR T. The first generations didn’t have a costimulatory domain. And then in second gens [generations], we added either 4-1BB or CD28. Third gens [generations] have 2 costimulatory domains, which had 4-1BB and CD28. The idea there is better T cell activation and more persistence. There was only 1 patient with CLL in this study and that patient had a CR [complete response]. Again, it’s the science aspect of this that I think is going to be the most interesting. The second CAR T study was of AUTO1. This was by Roddie [Claire Roddie, PhD, MD University of London, London, United Kingdom] and colleagues, presented at ASH. Again, a scientific breakthrough, I think, as opposed to a clinical right now. Only 1 patient with CLL was studied in this trial. The claim to fame with AUTO1 is that it has a fast dissociation with CD19, and so it binds to CD19 very quickly but then comes off a little bit quicker than our previous CAR T cells. And the idea is that, perhaps, we’ll have less cytokine release syndrome [CRS] and less neurotoxicity. In fact, in these small numbers, we saw no neurotoxicity, and there were no cases of grade 3 or higher CRS that they reported. I think something to just keep an eye on with CAR T and CLL, but at this point, I didn’t see anything at ASH that is going to lead to something in clinical practice in the next year or so.

I think that leads me into another exciting or up-and-coming pharmacological class: our bispecific drugs. I think epcoritamab. Looking at the epcor [epcoritamab] trial, from what was published at ASH, this is really looking at again, bispecific antibodies. This is nothing new in oncology care. But it’s, again, something new, definitely, to the CLL patient population. Looking at this bispecific therapeutic, it’s really looking at potent activation and cytotoxic activity through CD4 positivity and CD8-positive cells, so really trying to incorporate that into that CLL patient population. The clinical trial that was presented was by Kater [Arnon P. Kater

 MD, PhD, of Cancer Center Amsterdam, Netherlands] and colleagues, was a phase 1B2 trial trying to evaluate dose-limiting toxicities and early, early signs of clinical efficacy of epcoritamab in the relapsed/refractory CLL patient population. The eligible patients, or the patients that they looked at, had to receive at least 2 or more lines of therapy for CLL, so that could’ve been BTK [Bruton tyrosine kinase], BCL2 [B-cell lymphoma 2], etc. Ultimately, they had 2 types of dosing schemas. One was at 24 milligrams and 1 was at 48 milligrams. And what the data suggested is that those levels up to that 48-milligram had good clinical activity in patients with high-risk features and were well tolerated. Now, notable things that they did observe in this clinical trial; cytokine release syndrome happened in almost all the patients that were observed. Again, it was a small subset of patients in this clinical trial. They did see some fatigue, injection site reactions, and nausea. But all that CRS that did occur was predominantly during the first cycle, and there were really no CRS events that were deemed to be higher than a grade 2, so generally well-managed. But also, as Dr Perissinotti said, these therapeutics, CAR T, bispecific therapeutics, our noncovalent BTK inhibitors, and even our newer PI3K [phosphoinositide 3-kinase] inhibitors, all these things are in the pipeline, but we’re starting to evaluate these in terms of, could we use these next? From what we saw at ASH, none of these therapeutics are yet in line to replace that standard of care frontline therapy that we mentioned, or even in that second-line setting, from the efficacy data that we highlighted here today.

Experts discuss the potential future use of CAR T-cell therapy and bispecific therapeutics for chronic lymphocytic leukemia based on data presented at ASH 2021.

CAR T for Chronic Lymphocytic Leukemia

An exciting concept in CLL [chronic lymphocytic leukemia] are noncovalent binding BTK [Bruton tyrosine kinase] inhibitors. We’re all ready, I think, blowing everybody’s mind with all the data in terms of BTK inhibitors, but we’re going to add even more BTK inhibitors. But what benefit do these noncovalent binding BTK inhibitors have? I know there are some mutations there that these could potentially benefit from. What did we see at ASH [American Society of Hematology 2021 Annual Meeting] about these therapeutics?

: I think the most exciting right now is pirtobrutinib. As you said, they’re noncovalent binding. They’re irreversible binding. But, honestly, I don’t know pharmacologically that that is really what matters. I think the most important things about pirtobrutinib are, number 1, it’s more selective to BTK, even more selective than an acalabrutinib [Calquence] and zanubrutinib [Brukinsa]. So much more selective. And number 2, the half-life. Ibrutinib [Imbruvica], acala [acalabrutinib], and zan [zanubrutinib] have a very short half-life; they have to covalently bind to BTK, and they just need to shut down BTK until you produce more BTK. But pirtobrutinib, being a reversible BTK inhibitor, needs a long half-life so that you’re constantly binding BTK. And then if you create more BTK, or there’s high cellular turnover, it’s still going to be around and it’s going to bind to BTK. Those are the 2 claims to fame of pirtobrutinib: selectivity and longer half-life. So how do I treat a patient who’s double exposed? So it's a clinical trial—a clinical trial with something like pirtobrutinib. Now, if I don’t have a clinical trial, what am I doing? I’m really thinking long and hard about what their previous therapy was and why they came off therapy. Was it for progression? For example, did the patient actually progress on venetoclax [Venclexta]? Did they not get a durable remission? If the answer to that is no, and yes, they had a durable remission, I would retreat them with venetoclax. Or, if you have a patient that just didn’t tolerate their BTK inhibitor, I would switch around their other BTK inhibitor and not necessarily move on to the next line of therapy. But, if it was truly a patient that progressed, and was completely intolerant to all BTK inhibitors, clinical trials is where I would go, and pirtobrutinib has some excellent data that was presented at ASH. So this is the BRUIN study. The BRUIN study had multiple different arms. They had a CLL and a mantle cell [lymphoma] arm. I’ll focus on the CLL arm. This is a phase 1/2 study in patients that have relapsed/refractory CLL. All patients received a BTK inhibitor, and many patients were refractory also to both BTK inhibitor and venetoclax. There was about 170 patients in this study. And despite being that refractory, about 63% of patients had an overall response. If you follow patients longer, we know from BTK inhibitors that responses do take some time. In patients that had at least 10 months of follow-up, that overall response rate moved from 63% up to 86%. So this is a very, very effective therapy that I think is going to hopefully get FDA [Food and Drug Administration]-approved in the next year or so, so that our patients who are double-exposed in double-refractory have an additional option so that they’re not having to use chemotherapy, and they’re not having to use PI3K [phosphoinositide 3-kinase] inhibitors like idelalisib [Zydelig]. Because, as you mentioned, the toxicities are not that great. But Dr Hanna, there is a nice new PI3K inhibitor, umbralisib, that was presented at ASH. Talk about that agent, how it’s different than our other PI3K inhibitors. You kind of ragged on the toxicity. Do we see that also with this new therapy?

Dr Perissinotti, we have a novel PI3K inhibitor that is already FDA-approved in other B-cell malignancies. But umbralisib, there was actually some phase 2 data, really exciting in the CLL population; really interesting approach, too, not just looking at umbralisib, but they call it the U2 combination, but really focusing on umbralisib and how it’s distinguished from other PI3K inhibitors like idelalisib or duvelisib [Copiktra]. Its claim to fame is that it’s more selective, thus leading to off-target, again, kinase activity, potentially leading to a safer AE [adverse event] profile. So this is very selective to PI3K and casein kinase 1-epsilon as well. Again, more targeted, just really trying to focus on those fewer side effects, but really looking at the phase 2 data, looking at umbralisib in this patient population. What they wanted to do in this phase 2 trial—again, it was a small subset of patients, it was 26 patients that were recruited in this phase 2 trial, just really beginning to evaluate some efficacy signals—is that they treated patients with CLL with ibrutinib. For patients that did not achieve MRD [minimal residual disease] negativity, which again, in BTK monotherapy treatment, you don’t get a lot of MRD negativity, as all of us pretty much know. But what they did in this clinical trial is that they had this lead-in approach. And what they did in this patient population is that they added umbralisib, as well as ublituximab, and that’s why it’s called U2. Both begin with a U. And ultimately, what ublituximab is, it’s a novel anti-CD20 monoclonal antibody. It is glycoengineered for enhanced antibody-dependent cellular cytotoxicity, so really trying to—the goal here was to induce undetectable MRD, minimize the potential risk of developing BTKi [Bruton tyrosine kinase inhibitor] resistance or mutations, and maybe even stopping all the CLL-directed therapies and to see what type of durable response. This is a very, very early study with a very small subset of patients. But what they noticed in this clinical trial is, again, in CLL, this is the first MRD-driven approach, not so much of treating patients and then evaluating what their MRD outcomes were, but it was more of treating patients, looking at MRD, and then changing therapy based on MRD. It was really interesting to see that. And what they saw was promising; tolerability and efficacy signals, whereas that undetectable MRD negativity was achieved in 71% of patients that got that addition of U2 to ibrutinib. So pretty exciting. But I would take it as a small subset of patients. Again, we don’t really know the full extent of MRD negativity and what that means in terms of outcomes, so it’s going to be exciting to see what will come from this.

Dr Anthony Perissinotti details an effective new therapy on the horizon in chronic lymphocytic leukemia.

Noncovalent Binding BTK Inhibitors for Chronic Lymphocytic Leukemia

We’ve discussed tons of information. We’ve talked about BCL2 BTK [Bruton tyrosine kinase]. We’ve talked about finite treatment durations. We’ve talked about long-term efficacy from BTK and BTK plus anti-CD20. Clearly, this landscape is becoming extremely crowded and the treatment algorithms are becoming more complicated. Walk us through treatment selection strategies for a patient with CLL [chronic lymphocytic leukemia].

The unbiased opinion is to throw venetoclax and obinutuzumab into a hat with ibrutinib, acalabrutinib, and zanubrutinib, and pick 1 out. Honestly, that’s the right therapy for the patient—these are all fantastic options. My preference is to use venetoclax with obinutuzumab. The reason is that you have a fixed duration. You’re going to treat these patients in the frontline setting for only 1 year. Based on CLL14, the majority of your patients 4 years later are still going to be off therapy. No. 1, patients are going to be off therapy. They’re not going to have adverse effects from a therapy they’re not on. No. 2 is the cost of therapy. There was an analysis published that looked at a variety of regimens: ibrutinib-based regimen vs FCR [fludarabine, cyclophosphamide, rituximab] vs chlorambucil-obinutuzumab vs venetoclax with obinutuzumab, so the CLL14 study. On a 3-year horizon, you’re looking at about $350,000 for venetoclax-obinutuzumab, which sounds like a lot until you go and look at the BTK inhibitors. You’re looking at $500,000 to $600,000 over a 3-year horizon for most patients.

Based on RESONATE-2 data presented at ASH [American Society of Hematology Annual Meeting], roughly 60% of patients are still on therapy at 7 years. With a horizon of 7 years, you’re looking at millions of dollars. From a cost perspective, the majority of patients should get a finite therapy of venetoclax-obinutuzumab. That being said, the elephant in the room is COVID-19. None of us wants to bring our patients into our infusion centers to receive obinutuzumab. Most of us are trying to avoid an anti-CD20 monoclonal [antibody] because of vaccine responses, so it’s very appealing to write a prescription for a BTK inhibitor, send the patient home, and do virtual visits. That’s the challenge with COVID-19. We have swayed toward using single-agent oral therapy because of it.

Other patients for whom I’d consider a BTK inhibitor are those with 

 mutations. The [University of Texas] MD Anderson [Cancer Center] presented its data at ASH. It was about 6 years of follow-up, and 60% of patients are progression-free despite having a 

 mutation. This is very similar to RESONATE-2. Essentially, your 

 patients are doing as good as any other patient with CLL if they’re treated with a BTK inhibitor. A 

 mutation sways toward a BTK inhibitor for me, as opposed to venetoclax.

Then the question is which BTK inhibitor do you choose? We’ve been using ibrutinib for almost a decade, so we have a lot of personal experience with it. Most of our patients were still using ibrutinib. If there’s any patient we’re worried about who has comorbidities or cardiovascular disease, and we’re worried about long-term complications, if this patient does get A-fib [atrial fibrillation] or hypertension, what’s that going to mean for their long-term outcome? We’re swaying toward using our second-generation [BTK inhibitors]. As I said, some institutions have abandoned ibrutinib and are going on because the data support that. The data support that BTK inhibitors or second-generation [BTKs] are better tolerated.

What about at your center in the front line? Anything? I don’t want to give my own bias, but that’s my interpretation of the literature. That’s what I’m looking at for patients. Being off therapy and the cost of therapy are 2 of the most important things, from my perspective, [along with] your ability to manage the toxicities. If you’re comfortable preventing or managing the toxicities, I don’t think ibrutinib is a bad option. But if you’re uncomfortable, and you only treat a few [patients with] CLL per year, you probably should move on to second-generation [BTKs]. What are your thoughts?

 I totally agree with you, Dr Perissinotti. It’s really exciting. In CLL, we can almost say that our patients are going to succumb to older age or other comorbidities not related to their disease. We have numerous exciting options. But I’m in favor of what you’re saying and more in favor of finite treatment duration. You limit costs, you limit treatment exposure, you limit adverse event [AE] potential. We know from what we’ve learned that these patients can still respond to some of the therapies that we’ve already used in the finite approach vs telling someone you’re going to be on ibrutinib for 8, 9, 10 years. It poses a challenge.

That brings us into the bucket of some challenges we’re seeing in the CLL patient population, which will also help us segue into future perspectives of CLL. One challenge we’re seeing predominantly in CLL is that if you have a patient who’s double exposed, and you’ve exhausted your BTK and BCL2, what now? Do we go PI3K? Do we go chemoimmunotherapy? This is where we have some challenges with PI3Ks. We’re going to talk about some exciting things coming up, but PI3Ks are hard to tolerate, at least the ones that we have that have been FDA approved in CLL or more widely utilized, and they’ve really fallen out of favor.

We see a lot of immune-related adverse events or adverse events that [result from] immunotherapy, something like a pembrolizumab, for example. We see a lot of colitis, a lot of GI [gastrointestinal] involvement, and a lot of other AEs that many patients aren’t used to when they were on BCL2 or BTK. By this time, they’re older, they’re more frail, and they have more comorbidities, so chemoimmunotherapy is not a very good option for many of these patients. What do we do? Do we enroll them in a clinical trial looking at all the exciting approaches we’ve seen? Is 1 patient more appropriate than another? It becomes very challenging. But in clinical practice, I’m not seeing many patients for whom I think about a third-line setting. That’s really exciting to say about CLL in this day and age.

Anthony Perissinotti and Kirollos Hanna discuss considerations for selecting treatment regimens in chronic lymphocytic leukemia.

Treatment Selection Strategies for Chronic Lymphocytic Leukemia

Let’s segue into an important concept: tumor lysis. You mentioned that these patients may have leukocytosis at baseline or come with a very high ALC [absolute lymphocyte count] and that ultimately, when you give therapies, they see leukocytosis, etc. When we talk about tumor lysis, the biggest drug we’re going to focus on is the BCL2 inhibitor venetoclax. For our listeners, when we talk about tumor lysis prevention, the patient at most risk is going to be that person on venetoclax. But when you look at the CLL14 and MURANO trials, the clinical incidence of TLS [tumor lysis syndrome] was 0%. With laboratory TLS, you had some changes in their lab parameters, so we saw very low numbers there. When you follow the appropriate titration schedule of venetoclax, it’s a 5-week titration and not the same as the AML [acute myeloid leukemia] dosing. That’s very important. Or if you debulk them with your anti-CD20 first as 1 of the approaches, that’s going to be very important and a key to success to lead to that 0 incidence of clinical TLS.

There are [some] things we have to focus on in terms of evaluating our patients for tumor lysis. What is their absolute lymphocyte count at baseline? What are their lymph node sizes at baseline? How many lymph nodes throughout their system do they have? What are their baseline laboratory parameters? [What does their] organ function look like? In terms of your absolute lymphocyte count, if you have a patient greater than 25,000, you’re probably going to treat that patient as a moderate-risk patient, potentially even a high-risk patient, if they have other factors that increase the risk for developing tumor lysis.

In terms of their lymph node size, there are 3 categories: 5 cm or less, 5 to 10 cm, and greater than 10 cm. How many of these lymph nodes are there? That’s going to be a clinical assessment call. If I have a patient with 3 or 4 lymph nodes, all 7 cm, I’m probably going to treat them as high risk, moderate risk, or on the higher end of moderate. Lastly are your baseline labs: what does the creatinine look like? What does the renal function look like? What does their baseline uric acid look like? Then [we look at] various electrolytes—your calcium, your phosphorus, your potassium. Based on these assessments, you’re able to put your patient in different buckets, whether it’s low risk for TLS, moderate or intermediate risk for TLS, or high risk for TLS.

Those higher-risk patients are the most concerning. Those are the patients you may consider admitting and treating with aggressive fluid hydration. If you have a high-baseline uric acid, maybe something like rasburicase prophylactically or right from the get-go with this patient population. All these patients are going to require antihyperuricemics with allopurinol. We’ll talk about pharmacy considerations later, but it’s also very important to avoid drug-drug interactions, especially during the ramp-up phase of venetoclax.

Your low-risk patients are on the other side of the spectrum, as long as they can stay hydrated, adhere to the ramp-up schedule, and adhere to their laboratory schedule. You’re going to have to evaluate labs more frequently as you’re ramping up, especially on those first days of each ramp-up level—sometimes predose, 6 to 8 hours in, 24 hours later—to make sure. If you’re high risk, you’re evaluating it much more frequently. In terms of tumor lysis syndrome, all these things are going to be very important considerations for your patients. Mr Perissinotti, is there anything different that you’d consider for TLS?

No, you perfectly articulated all that. To summarize, you have patients who are high risk, intermediate risk, or low risk for TLS. For high-risk patients and some of your intermediate risk, unfortunately, you have to admit those patients for extra monitoring. There was an ASH [American Society of Hematology Annual Meeting] abstract based on the CLL13 trial, a study that had multiple arms—well, 3 arms had a venetoclax-based regimen. They did the trick that Mr Hanna talked about and did a lead-in with your anti-CD20 monoclonal. They did about 3 doses of obinutuzumab or obinutuzumab with ibrutinib before starting venetoclax. They ended up finding is that a substantial number of patients were able to be reduced from that high-risk category down to intermediate, and some intermediates down to low risk. What that means clinically is probably nothing. As Mr Hanna said, the risk for TLS is still pretty low based on our dose escalation. What that means logistically is that you no longer have to admit your patient into the hospital to administer their first dose and then the second week of their dose escalation of venetoclax. I like how we now have data from CLL13 that this strategy is effective.

Chronic lymphocytic leukemia experts debate how to prevent or reduce the risk of tumor lysis in patients.

Tumor Lysis and Chronic Lymphocytic Leukemia

Mr Perissinotti, in your practice, what would it be a good clinical scenario to incorporate an anti-CD20 monoclonal antibody?

 I agree with everything you said. For any patient who’s receiving venetoclax, I would. If you’re following the CLL14 study, and you’re trying to get deep remissions, and you want to keep your patient off therapy for as long as possible, the anti-CD20 and obinutuzumab are going to deepen your remission. Venetoclax is an absolute. Even MURANO used rituximab. It’s a little less clear whether you need rituximab or obinutuzumab in the relapse setting, especially if you already previously received it. Let’s follow the data.

With the BTK inhibitors, there isn’t any clear guidance from the literature as to who’s going to benefit from a monoclonal antibody. Open questions are, did the Alliance [for Clinical Trials in Oncology] trial have no difference because rituximab [Rituxan] was the problem? Did you need to use obinutuzumab, something with more antibody-dependent cellular cytotoxicity [ADCC]? Maybe it’s ibrutinib, which inhibits ITK and can reduce ADCC and inhibit the mechanism of rituximab. Maybe you shouldn’t use a monoclonal with rituximab. Being able to compare, contrast, and extrapolate whatever happened with rituximab or ibrutinib with obinutuzumab and acalabrutinib is tough.

The ELEVATE-TN trial pretty much tells you the story: there’s a very marginal benefit. Even at the 4-year update that was recently published, it’s a marginal benefit. I agree completely with you with COVID-19: going in and out of the hospital is not ideal. Vaccine responses with obinutuzumab are next to nil. That’s not ideal for our patients.

Going back to your question of where I would consider using it: with a BTK inhibitor. If I have a patient with CLL [chronic lymphocytic leukemia] with a tremendously high white blood cell count—let’s say they present with a white blood cell count of 700,000 per mm3—that patient is going to have lymphocytosis from their acalabrutinib or ibrutinib, and it’s going to skyrocket to into the millions. That makes me a little concerned. I want to debulk that patient to bring it down as much as possible. It freaks me out. Clinically is that going to end up leading to leukostasis or tumor lysis? Probably not. But it would make me feel a lot better if the white blood cell count wasn’t rising to the millions. That’s 1.

If I have a patient who needs a quick response—they have really painful lymphadenopathy, or they’ve got a packed marrow and pancytopenia—and I think a BTK inhibitor is appropriate, and I might consider using obinutuzumab in that setting as well. It’s not evidence based at all; it’s anecdotal of what I do. That’s that teeny-tiny percent—99% of my patients would not get an anti-CD20.

Anthony Perissinotti, PharmD, BCOP, explains potential scenarios requiring anti-CD20 monoclonal antibodies as a therapy for chronic lymphocytic leukemia.

Kirollos Hanna, PharmD, BCPS, BCOP

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