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Challenges with BTKis in CLL, MCL, and SLL

A panel of experts discuss the provider, payer, and patient challenges that must be considered with BTK inhibitors in chronic lymphocytic leukemia, mantle cell lymphoma, and small lymphocytic lymphoma.

Ryan Haumschild, PharmD, MS, MBA: We know there are also challenges, and you kind of highlighted those but maybe you could talk us through [in more detail]. What are some of the other challenges you need to consider when you’re starting a patient on a BTKi [Bruton tyrosine kinaseinhibitor]? It might be working with a cardio-oncologist, or there might be additional follow-up needed with patients. If you could, talk us through some of the provider challenges with the adverse event profiles between these agents.

Callie Coombs, MD: There certainly are challenges. The first is getting the drug approved so that obviously can be colored by whomever the patient is insured by. It can be difficult for uninsured patients, though I’ve often worked with drug companies and have been able to get manufacturer assistance. Once we do get the drug, we do worry about these toxicities. With the cardiac adverse effects, it’s often important to understand the patient’s risk of these complications. Atrial fibrillation is the most common, arrhythmia can come up, but there are also ventricular arrhythmias that fortunately are rare, but they are seen more with ibrutinib than acala [acalabrutinib] based on cross-trial comparisons. Still very rare events, though they have occurred also in a lot of the studies we’ve seen. We also don’t want to worsen any existing conditions. So if a patient has poorly controlled hypertension, I do get nervous about putting them on any BTK inhibitor, but more nervous with ibrutinib with the higher rate. Another concern is once zanubrutinib is approved, what do you pick between zanubrutinib and acalabrutinib, given that they both have superiority to ibrutinib but we don’t have head-to-head data? I did try to emphasize how different the trial populations were, so I don’t think one can conclude zanu [zanubrutinib] is definitely better than acalabrutinib, but I do think they both have advantages over ibrutinib that lead most CLL [chronic lymphocytic leukemia] doctors to tend to favor the newer drugs because we want to have the safest drug possible for our patients.

Ryan Haumschild, PharmD, MS, MBA: Dr Coombs, you did a great job. I think you’ve outlined the benefits of BTK inhibitors, those that are safer, or so we can decide between 2 agents. But sometimes treatment does get hung up in some of those payer challenges. Dr Beveridge, being a managed care executive, I’m curious from your perspective, what are some of the payer challenges you have when evaluating these BTKi? Is there enoughavailableevidence, is there any efficacy, or safety information you’re considering?

Roy Beveridge, MD: I do have some worries. Most FDA trials look at populations who are significantly healthier than the normal patient who’s going to be taking a BTK drug. When we looked at Humana or UnitedHealthcare, or any of the large nationals, patients coming off an FDA trial will have 1 or 2 comorbidities; the normal patient population with CLL has 5 to 7. Hypertension is almost universal in this population, and A-fib [atrial fibrillation], A-flutter [atrial flutter], etc, is much more common. So one thing that the payer community urges and is doing itself is looking at real-world evidence and saying look, United has classically done this for a long time. We’ll look at this BTK, and this BTK, in terms of the 2 new ones, and then look at the old one and say, for a patient population with 5 comorbidities, this is what we’re seeing. This begins to drive some of the conversations.

There’s still a hesitancy in too much of academic medicine, in my opinion, to not contribute and engage in real-world evidence. It is a big problem for say, the Medicare Advantage population. If we want to talk a bit about the Medicaid population, I would remind people that there are 90 million Americans who have Medicaid right now. And 20 million of them are going to lose their Medicaid insurance over the next year once the public health emergency disappears as of April. So when you’re talking about worrying about your Medicaid patient getting a prescription, you’re going to have 20 million more people who have no insurance who will have even fewer options to engage. That’s what I think the payers worry about.

Ryan Haumschild, PharmD, MS, MBA: It’s helpful to know the payer perspective as well, especially when we’re looking at this. But one of the most important ones I feel like is the patient perspective. Dr Koffman, I’m going to turn to you for that. If you could, provide a bit of background on what are some of the patient access challenges in terms of ease of access and dosing that usually come up with these BTKi?

Brian Koffman, MD: I think it’s easy to hit that one out of the park because the biggest problem for a lot of patients is the financial toxicity of these. So even if you have good insurance, if you have traditional Medicare, the co-payments can be very difficult for a lot of patients. And it’s very difficult for patients to get support. It’s possible to get support, but it’s not certainly guaranteed. I’ve certainly seen patients and their clinicians make a decision based on the fact that the patient can’t afford what might be their best choice. Instead, they’re being put in a chair and getting an infusion of cytotoxic chemotherapy because that’s paid for in a different part of Medicare. So that’s a real problem for patients.

The other thing that’s less of an issue, but is a significant issue, are things like arthralgias and myalgias; patients get sick of that, especially when they’re taking medicine that they’re taking until they progress. When you look at the data on ibrutinib, in most studies the main reason for patients stopping is intolerance, not disease progression. So are there ways to manage that? Can you work with the patient? If they’re doing great on that medicine, can you find ways to help them cope with their muscle aches and pains, to control their blood pressure, if there’s a cardiac issue can you control that? Do you switch to a different medication? These are issues I think the patients face. First is the financial toxicity, and second is the annoying adverse effects. It’s clear if your patients have significant cardiac arrhythmias, they have to stop. But is there a way you can keep them on a medicine that’s working for them? However, they feel miserable.

Ryan Haumschild, PharmD, MS, MBA: You highlighted so many things that I’m passionate about as well. Financial toxicity, if you can’t get the medication to the patient, then you can’t get started. I think that’s so important, especially when we think of social determinants of health. There are so many vulnerabilities patients have when they’re trying to seek treatment. You also brought up a great point, making sure patients stay on therapy as long as they need to. If a patient gets a rate-limiting adverse effect or some type of toxicity, is there something we can do to offset that, to keep them on therapy longer, because we know that there are great durable responses when they can get there? I appreciate you bringing up those points.

Transcript edited for clarity.

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