Ryan Haumschild, PharmD, MS, MBA: As so many therapies come into this space, one question that arises is, how do we choose between these? How can we pay 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 are asking, and I’m curious about your thoughts, what’s the value of direct classroom clinical trials instead of placebo and standard care? Are there any direct studies you would like to see in mantle cell lymphoma? I’d like to hear some of your thoughts on that.
Michael Wang, physician: Head-to-head clinical trials are very important. For example with zanubrutinib in a mutual comparison in a Waldenström [macroglobulinemia] randomized trial, efficacy was similar, but toxicities were different. In another direct clinical trial with acalabrutinib versus ibrutinib in CLL [chronic lymphocytic leukemia]there are also comparable efficacy and different toxicity profiles.
There is no direct comparison with mantle cell lymphoma because mantle cell lymphoma is rare, and when we compare the therapies we need a large population, which takes years. We must try to survive without the mutual comparisons. But there is a direct comparison in the LOXO-305 trial, a phase 3 randomized clinical trial. One arm is pirtobrutinib and the other arm is the investigator’s choice for the covalent BTK [Bruton tyrosine kinase] inhibitors. dr. Jain and I think that’s the mutual comparison. dr. Jain tried to enroll a patient in this study yesterday. We eagerly await the outcome of this trial.
Preetesh Jain, MBBS, MD, DM, PhD: I totally agree with Dr. Wang. It is clear that several groups are working on randomized studies of mantle cell lymphoma, with a larger group consisting of the United States and Europe together. There are studies that combine rituximab maintenance versus ibrutinib maintenance versus no maintenance after first-line therapy has been completed. Those combinations are coming, but because it’s a rare condition, approval takes time and it takes a long time to answer those questions.
Ryan Haumschild, PharmD, MS, MBA: Dr. Jain, I have one more question for you, because you do 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 look at data. What is 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 of the ibrutinib trial, a pooled analysis with very large data points. Longer term follow-up shows the percentage of patients who discontinue treatment, and 90% of patients do not use ibrutinib in the relapsed setting after 10 years of follow-up due to either progression or intolerance. We also reported our long-term follow-up after ibrutinib discontinuation. If you look at the cumulative incidence, the most common reason is progression and then intolerance, and then there are different patient preferences in the relapse setting. If you look at the longer follow-up of acalabrutinib, Dr. Wang’s report, and the longer follow-up of zanubrutinib, which was released last month in Blood, we see a pattern of patients, 60% of even those on acalabrutinib and zanubrutinib in the relapsed setting, quitting. You have to look at intolerance. Our first-line studies with a longer follow-up will be reported, so those data will be interesting regarding what happens with BTK inhibitors in the first-line setting. A longer follow-up is important.
Ryan Haumschild, PharmD, MS, MBA: It sounds like, based on some of the reasons patients are discontinuing therapy, we can get more pharmacists involved in helping the teams manage those toxicities because there’s an opportunity to improve patients and their ability to stay in therapy. keep improving. You never want to see a patient progress from therapy, but you would rather see them progress than discontinue therapy due to toxicity or non-adherence to therapy. That’s a great point. Long-term follow-up is not only valuable to the patient, it is also valuable to us as healthcare providers and to the payer or insurer trying to keep that patient alive, provide them with the best therapy for their illness and make coverage arrangements. feed. That.
Transcription edited for clarity.