A broad review of BTK inhibition as a novel therapeutic approach toward the treatment of marginal zone lymphoma.
Bhavesh Shah, RPh, BCOP: We now have 2 BTK [Bruton tyrosine kinase] inhibitors in this area. Obviously, there are more than 2 BTK inhibitors, but we have at least 2 approved in this setting. Javier, thinking about the differences in the BTK inhibitors and adverse effect profiles, how do you choose which BTK inhibitor to use from your perspective?
Javier Munoz, MD, MBA: Excellent question. My experience has been positive with BTK inhibitors in general. Regarding marginal zone lymphoma, there was a phase 2 study addressing single-agent ibrutinib 560 mg per day. It was a small study of only 63 patients with relapsed/refractory marginal zone lymphoma. The overall response rate was 58%, which is attractive. The median duration of response was 27.6 months, which is very attractive. The safety profile was consistent with prior reports. The most common grade 3 or higher event was anemia in that particular trial.
When it comes to zanubrutinib, which was recently FDA approved for marginal zone lymphoma, we have the results from the MAGNOLIA trial. Amit is going to comment a little more about that study in a second. The overall response rate was 60%, and responses were seen in all subtypes of marginal zone lymphoma. The median duration of response wasn’t reached. Was zanubrutinib stopped? Yes. The treatment discontinuation was mainly due to disease progression. The adverse effects were similar to what we have seen with other BTK inhibitors: diarrhea, easy bruising, and upper respiratory tract infections. Of note, atrial flutter was only seen in the single digits—1.5% in the MAGNOLIA trial—at least during the last data cutoff, the last rendition reported during ASH [American Society of Hematology annual meeting] 2020. Until then, no major bleeding events had been reported.
What comes to mind when you think about a BTK inhibitor is bleeding, atrial flutter or atrial fibrillation, and hypertension. It seems like these novel BTK inhibitors retain efficacy with a more favorable toxicity profile. We’re starting to get results, including randomized data from several lymphoproliferative disorders, like Waldenstrom macroglobulinemia and chronic lymphocytic leukemia. It’s tempting to extrapolate. I don’t think the novel BTK inhibitors are necessarily more efficacious, but they probably have a safer toxicity profile.
Bhavesh Shah, RPh, BCOP: It’s amazing. We continue to expand on what we have in terms of more selective higher BTK occupancy in the lymph nodes and the PBMCs [peripheral blood mononuclear cells]. We haven’t seen a clinical difference in responses, but we’re seeing differences in adverse effects. It’s amazing how we continue to evolve, making these treatments even better.
Transcript edited for clarity.