Monitoring and Managing Treatment Toxicity for Patients on Anti-CD38 Regimens


Toxicity management associated with anti-CD38 drugs is highlighted by a panel of medical experts.

Ryan Haumschild, PharmD, MS, MBA: Even with those toxicities, we want to make sure we are educating them but also monitoring them. Mr Hanna, how are you monitoring and managing treatment toxicity for patients on anti-CD38 regimens?

Kirollos S. Hanna, PharmD, BCPS, BCOP: With anti-CD38 agents, from what we learned over several years, there’s not much to do once your patient has gotten beyond a couple of cycles. I’m not saying there aren’t going to be toxicities that you need to manage. From a multidrug regimen perspective, you’re going to get your cytopenias and coagulopathies. But before initiating anti-CD38s it’s going to be key to obtain their blood type, typing and crossing our patients, although there are different ways to do it. That’s going to be 1 key intervention up front.

We want to make sure that these patients are any type of infectious prophylaxis that they may need as part of their regimen. But when you look at the history of anti-CD38s, when daratumumab came out, it was 3 to 4 lines into treatment and no one had an idea how we are going to fit this 8-hour-plus infusion into our infusion centers. People were talking about doing it at an inpatient-based center that’s still has outpatient billing. But we’re talking about eliminating premedications with X number of doses, and we’re doing subcutaneous infusions. What we’ve learned about CD38s from a safety perspective is that once patients have been exposed to 2 or 3 doses of the therapy, whether it’s daratumumab or isatuximab, they tolerate it just fine.

There are not-so-common adverse effects that I’ll talk about in a bit, but there are 2 key studies I want to highlight. One study published in JHOP, the Journal of Hematology Oncology Pharmacy, with HOPA [Hematology/Oncology Pharmacy Association] demonstrated that you can omit the premedications with daratumumab. I can’t remember if they did subcutaneous or IV [intravenous]. There was also a poster presented at ASH [American Society of Hematology] Annual Meeting that did it with the other formulation. I believe ASH was subcutaneous and HOPA was IV, and both represented that going forward with daratumumab after 3 doses, you can safely omit premedications.

Even before these data, we had publications that allowed us to safely administer daratumumab during those first 2 doses or even potentially isatuximab. [There are] not many studies, but you can apply these same concepts to drugs like montelukast. Fexofenadine is blended, but these are things you can incorporate from premedication to mitigate some of those infusion-related reactions. When a patient has an infusion-related reaction, pharmacists have an opportunity to provide education in terms of how you’d treat those types of reactions, but it doesn’t increase the risk or anything for subsequent infusions. For some of our drugs in the infusion center, we say that if a patient has had a prior reaction, they aren’t eligible for rapid infusion in the future. With daratumumab, we don’t care. Even if they reacted as expected—from 30% to 40%, even upward of 50%, regarding the CD38—they’re going to react whether it’s dose 1 or 2. Dose 1 has the highest risk. Those are important things to consider.

Look at daratumumab and at the PI. Some of the data say to administer steroids on day 2 and 3 because you can see delayed reactions. But beyond those first couple of dosages, you don’t even see that, so sometimes we can simplify myeloma regimens. Instead of giving steroids, your patient is taking 40 mg of dexamethasone weekly. Instead of doing that steroid 20 mg prior to daratumumab and 20 mg the day after—or however you potentially do it—give him 40 mg weekly. You don’t even need to time it around the daratumumab because they’re not going to have a reaction.

Pharmacists bring in great considerations in terms of how you should monitor patients around the subcutaneous formulation. You administer the subcutaneous formulation, and you look at the heterogeneity across the country of what you should do in terms of monitoring. Look at the Mayo Clinic, what I do at University of Minnesota, what some people do in South Carolina. Ms Maples and I were talking at HOPA Annual Conference several months ago, and we heard that some people weren’t doing any type of observation. After first administration, your patient can have a reaction within the first 3.5 or 3.7 hours; in subsequent doses, not so much. Those are areas where there’s some education. The last thing you want to do is give your patient that subcutaneous administration, and they have some type of reaction on their drive home, and a fatal event occurs.

I talked about some rare things that could occur. With neutropenias, they’re on a multidrug regimen. If you’re on IMiDs [immunomodulatory imide drugs] in combination with these drugs, that’s the most causative agent for cytopenias. I’ve seen a rare case of profound neutropenias with daratumumab. We’ve had a couple of patients on those. We’re talking severe neutropenias, but tolerability beyond getting them those first 3 doses is smooth sailing across the board.

Ryan Haumschild, PharmD, MS, MBA: We’ll continue in our discussion around toxicities. Mr Hossain, renal impairment is common in patients with multiple myeloma. How does the presence of renal impairment impact treatment decisions in multiple myeloma, particularly anti-CD38 therapy? Discuss your recent real-world data on renal function in patients with multiple myeloma and what can be done to prevent or slow the loss of renal function?

Shahrier Hossain, PharmD, BCOP: In our practice, we’re big on quads no matter what. If we can’t give you daratumumab–RVd [lenalidomide, bortezomib, dexamethasone] in that setting, we’ll give you daratumumab–CyBorD [cyclophosphamide, bortezomib, dexamethasone] until things are a little more calm. But renal impairment can mean a lot of different things, from CRT [cardiac resynchronization therapy] to dialysis to a creatinine clearance of less than 30 mL/min. Depending on the situation, if the patient is acutely ill in the hospital, we may do CyBorD [cyclophosphamide, bortezomib, dexamethasone] or Vd [bortezomib, dexamethasone] for cost-related issues, because daratumumab is more costly on the inpatient side than the outpatient side. But once they’re out of the inpatient setting and into the outpatient, we’ll add daratumumab or whatever anti-CD38 molecule we need to add.

Daratumumab has a lot of evidence in the renal impairment setting. There was an article that looked at patients in ICUs [intensive care units] that had multiple myeloma. Of those 15 patients who got daratumumab-RVd [lenalidomide, bortezomib, dexamethasone], I believe 12 or 13 ended up having at least VGPR [very good partial remission]. Six of those patients ended up on dialysis and then got off it, showing that these patients aren’t doomed. You can recover from renal impairment. You can potentially come off dialysis.

Another ASH abstract a few years ago looked at patients at Weill Cornell Medical College. They had a harder time looking at patients on dialysis, but they showed that patients with an eGFR [estimated glomerular filtration rate] of less than 60 mL/min did well on daratumumab-based therapy. Their overall survivals were roughly the same compared with those without renal impairment.

I want to point out that preventing renal dysfunction can be challenging. For pharmacists, it’s an opportunity to do medication reconciliation, to make sure patients aren’t on any nephrotoxic medications. I tell my patients that NSAIDs [nonsteroidal anti-inflammatory drugs] are everywhere, so be careful. I also tell patients to drink adequate amounts of water, which can be challenging if they have other comorbidities that may preclude the use of excessive hydration. Lastly, it’s always an option to think about bone-modifying agents. I shy away from bisphosphonates when a patient has renal impairment. I prefer to circumvent any adverse effects associated with Zometa.

Transcript edited for clarity.

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