The Evolving Role of BTK Inhibitors in the Treatment of Relapsed/Refractory Mantle Cell Lymphoma - Episode 11

Aligning Value-Based Care with Payer Considerations In MCL Therapy Management

Key opinion leaders evaluate treatment options for MCL while emphasizing payer considerations.

Ryan Haumschild, PharmD, MS, MBA: As so many therapies enter this space, a question that comes up is, how do we choose between them? How do we afford the cost of them? That’s a common question. I always like to see more therapies available because that’s better for patient care, but it’s a reasonable question. So some people ask, and I’m curious about your thoughts, what’s the value of in-class head-to-head clinical trials instead of placebo and standard of care? Are there any head-to-head trials that you’d like to see within mantle cell lymphoma? I’d like to hear some of your thoughts about that.

Michael Wang, MD: Head-to-head clinical trials are very important. For example, with zanubrutinib in a head-to-head comparison in a Waldenström [macroglobulinemia] randomized trial, the efficacy was similar but the toxicities were different. In another head-to-head clinical trial with acalabrutinib vs ibrutinib in CLL [chronic lymphocytic leukemia], there also are similar efficacies and different toxicity profiles.

There’s no head-to-head comparison with mantle cell lymphoma because mantle cell lymphoma is rare, and when we compare therapy head to head, we need a big population, which takes years. We have to try to survive without the head-to-head comparisons. But there’s a head-to-head comparison in the LOXO-305 study, which is a phase 3 randomized clinical trial. One arm is pirtobrutinib, and the other arm is investigator’s choice of the covalent BTK [Bruton tyrosine kinase] inhibitors. Dr Jain and I think that’s the head-to-head comparison. Dr Jain tried to enroll a patient on this trial yesterday. We’re eagerly looking forward to the outcome of this trial.

Preetesh Jain, MBBS, MD, DM, PhD: I totally concur with Dr Wang. Clearly, there are several groups working on randomized studies in mantle cell lymphoma, with a larger group consisting of the United States and Europe combined. There are studies combining, after the frontline therapy is done, rituximab maintenance vs ibrutinib maintenance vs no maintenance. Those combinations are coming up, but because it’s a rare condition, the approval takes time, and it takes a long time to answer those questions.

Ryan Haumschild, PharmD, MS, MBA: Dr Jain, I have another question for you, because you’re doing a lot of great work in this space. We know that mantle cell lymphoma has a smaller patient population. It’s more unique when we’re looking at data. What’s the importance of long-term follow-up studies in this patient population?

Preetesh Jain, MBBS, MD, DM, PhD: It’s very important. Dr Wang recently reported the 10-year follow-up on the ibrutinib study, which is a pooled analysis with very big data points. The longer-term follow-up shows the proportion of patients who are discontinuing, and 90% of patients aren’t on ibrutinib in the relapsed setting after 10 years of follow-up because of either progression or intolerance. We have also reported our long-term follow-up post–ibrutinib discontinuation. If you look at the cumulative incidence, the most common reason is progression and then intolerance, and then there are other patient preferences in the relapsed setting. If you look at the longer follow-up of acalabrutinib, the report by Dr Wang, and the longer follow-up of zanubrutinib, which was recently reported last month in Blood, we’re seeing a pattern of patients, 60% of even those on acalabrutinib and zanubrutinib in the relapsed setting, are discontinuing. You have to look at intolerance. Our frontline studies with longer follow-up are going to be reported, so those data are going to be interesting regarding what happens in BTK inhibitors in the frontline setting. Longer follow-up is important.

Ryan Haumschild, PharmD, MS, MBA: It sounds like based on some of the reasons patients are abandoning therapy, we can get more pharmacists involved in helping the teams manage those toxicities, because there’s opportunity to keep improving patients and their ability to stay on therapy. You never want to see a patient progress off therapy, but you’d rather see them progress than abandon therapy due to toxicity or not adhering to therapy. That’s a great point. Long-term follow-up isn’t only valuable to the patient, it’s valuable to us as providers and to the payer or insurer that’s trying to keep that patient alive, provide them the best therapy for their disease, and make coverage determinations off of that.

Transcript edited for clarity.