The Future of BTK Inhibitors

EP: 1.Overview of CLL, MCL, and SLL

EP: 2.Prevalence, Diagnosis, and Management of CLL, MCL, and SLL

EP: 3.Goals of Therapy for CLL, MCL, and SLL Patients

EP: 4.BTKi Landscape for CLL, MCL, and SLL

EP: 5.Challenges with BTKis in CLL, MCL, and SLL

EP: 6.Unmet Needs Addressed by BTKis

EP: 7.BRUIN Trial: Pirtobrutinib and the Impact of BTKis

EP: 8.Managing BTKis for Coverage

EP: 9.Resistance to BTKi Therapy

EP: 10.Financial Burdens of BTKi Therapy

EP: 11.BTKis in the Value-Based Care Models

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EP: 12.The Future of BTK Inhibitors

EP: 13.Final Thoughts on BTK Inhibitors

Ryan Haumschild, PharmD, MS, MBA: Dr Coombs, when we think about education around BTK [Bruton tyrosine kinase] inhibitors, the space is expanding, and a lot of good agents are coming. What’s that unmet need in terms of education for physicians and payers surrounding the use of BTK inhibitors?

Callie Coombs, MD: There are a lot of educational aspects that could make our collective lives easier. Things are very different for the community doctor who primarily sees patients with breast cancer, colon cancer, and lung cancer, and a couple with CLL [chronic lymphocytic leukemia] a year vs the academic doctor who’s laser focused on CLL. Pathways could be very helpful for community doctors, who have such a hard job. Those could be curated, perhaps by people intimately familiar with the data who are laser focused on the disease. That’s 1 potential benefit. The second is toxicity management. If you see 2 patients with CLL a year, you don’t get intimately familiar with how to manage these toxicities. That’s another area of education that could improve outcomes for patients, to the point where we don’t abandon the drug prematurely—we help manage and support. That would be another major benefit.

Ryan Haumschild, PharmD, MS, MBA: Ilike your discussion of the prospective management of these patients and therapies. We’re making sure if there are any dose reductions needed, any supportive care. We’re being proactive, making sure the patient has the best chance of completing that regimen as prescribed. That’s another great thing to highlight. Dr Beveridge, you deal a lot with the payer side. What education is needed around BTK inhibitors from a payer’s perspective?

Roy Beveridge, MD: What Callie just said is exactly right. People think that pathways have to be 100%. Most of us have learned that pathways should be followed 80% of the time. If you’re following pathways 100% of the time, you’re probably performing cookbook medicine. If you’re following a set of pathways 50%, maybe you’re not reading enough—80% seems about right from a classic experience. That’s where we need to get to because the first thing that my esteemed colleagues mentioned is that this is a very individual disease—the 97-year-old patient and the 37-year-old patient are fundamentally different. Within that cohort of 80%, there should be a commonality in terms of how we approach patients. About 10% or 20% of patients are going to be off pathway, and they’re going to be very different. They may be the stem cell transplant or something else. That should be perfectly acceptable to all involved.

Ryan Haumschild, PharmD, MS, MBA: We’re excited about the future of BTK inhibitors, especially the research on how we can best utilize them across the country, incorporate them within pathways, and better manage patients, so they can continue that regimen as prescribed. Lastly, newer agents that are coming can circumvent resistance better and provide better outcomes for our patients. I’m curious about this panel, what are you most looking forward to in the use of BTK inhibitors in the future? What’s next for these therapies in leukemia and lymphoma? Dr Koffman, can you get us started?

Brian Koffman, MD: As a patient, I’m extraordinarily grateful for this revolution in targeted therapies and having these BTK inhibitors. I wouldn’t be alive—that’s no exaggeration—if I hadn’t enrolled in a couple of phase 1 trials. I’m extraordinarily grateful for that. They’ve changed the therapeutic landscape in the last decade. As patient advocates, we want to see everybody get the benefits of these. The benefit of these is knowing when to use them. What testing needs to be done? And knowing how to keep your patients on them. What’s your choice? When can you do dose reductions? Things like this. We’re excited about the next generation coming on because they look like they’ll help with patients who develop resistance and also be extremely well tolerated. The last hope is that these drugs become increasingly affordable for patients. If we get all those things, I’m going to be thrilled as a patient and as a patient advocate.

Ryan Haumschild, PharmD, MS, MBA: I love your wish list. It probably aligns with a lot of what we’re all hoping for as well. Stay tuned because there are some good things coming down the line.

Brian Koffman, MD: I agree.

Ryan Haumschild, PharmD, MS, MBA: Dr Coombs, I’m curious about your thoughts.

Callie Coombs, MD: No. 1, I agree with everything Dr Koffman said. To expand on that, there are new developments. We use BTK inhibitors as chronic therapies. I’m also excited about: time-limited options combining BTK inhibitors with venetoclax to give patients a break from therapy. I’m excited about the next generation of knocking down BTK inhibitors. [There’s] pirtobrutinib, which is a noncovalent BTK inhibitor, and nemtabrutinib. I’m profoundly excited about both of those. But now we have a newer class of drugs: BTK degraders. It’s been amazing to collaborate with the scientists who develop these new concepts, bring them into the clinic, and watch patients benefit because I truly value my long-term relationships with patients. That’s why I became a CLL doctor. To have them live longer and better is a win for everybody.

Ryan Haumschild, PharmD, MS, MBA: Thanks for your work in ongoing research to bring these therapies forward. That’s always exciting—to have you be a part of that, we’re very appreciative. Dr Beveridge, what are you most looking forward to out of these BTK inhibitors?

Roy Beveridge, MD: I’ll echo what Callie and Brian said. When I did my fellowship—a long time ago—all my patients with CML [chronic myeloid leukemia] died, most with AML [acute myeloid leukemia] died, and all with ALL [acute lymphocytic leukemia] died. Those with CLL [chronic lymphocytic leukemia] lived a little longer, but their quality of life—in terms of getting recurrent infections and having anemia, and having not a very good existence—is so different now. We should all be grateful for these products. They have a seriously positive impact on the world.

Transcript edited for clarity.