Second-line Therapies in MCL: Regimens With BTK Inhibitors and BCL-2 Targeting Therapies

EP: 1.Disease Overview: Mantle Cell Lymphoma

EP: 2.Factors for Consideration in Treatment Decision-making for MCL

EP: 3.Mantle Cell Lymphoma Maintenance Strategies

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EP: 4.Second-line Therapies in MCL: Regimens With BTK Inhibitors and BCL-2 Targeting Therapies

EP: 5.BTK Inhibitors in Relapsed/Refractory MCL and Treatment Selection

EP: 6.CAR T-Cell Therapy in R/R MCL

EP: 7.Strategies for Sequencing and Combining Therapies in MCL

EP: 8.Advancements on the Horizon in Mantle Cell Lymphoma

EP: 9.Treatment Overview: Chronic Lymphocytic Leukemia

EP: 10.Acalabrutinib in CLL: Insights from the ELEVATE TN and ASCEND Trials

EP: 11.Zanubrutinib in CLL: The ALPINE Trial

EP: 12.Treatment Decision-making Among Second-generation BTKis in CLL

EP: 13.Updates from Patient-reported QOL and Matching-adjusted Indirect Treatment Comparisons (MAICs) Studies in CLL

EP: 14.Emerging Approaches in CLL

EP: 15.TRANSCEND CLL: CAR T-cell Therapy for CLL

EP: 16.The Potential Role of Venetoclax Combination Approaches in CLL

EP: 17.Considerations for COVID-19 in MCL and CLL

EP: 18.Anti-CD20 Regimens and Triplet Therapies in CLL

EP: 19.Pirtobrutinib and Other Non-Covalent BTK Inhibitors in the Treatment of CLL

EP: 20.Closing Remarks on Upcoming Data and Future Perspectives in MCL and CLL

Anthony R. Mato, MD, MSCE: Alexey, one more question for you about mantle cell lymphoma (MCL), talking about the wayside. There was a moment in time where drugs like bortezomib or lenalidomide were state of the art, and now I'm finding it harder to sort out how to use those drugs in MCL, particularly lenalidomide, which always had more activity than bortezomib, as a single agent. Can you talk about recent data for lenalidomide-based therapy in MCL and help us to figure out how or where to use this agent?

Alexey V. Danilov, MD, PhD: Certainly, I think the use of these agents declined mainly because of the advent of novel therapies [that] are much more effective, like BTK inhibitors, to some extent, BCL-2 inhibitors, [and] the newer drugs as well as novel agents in clinical trials like bispecific antibodies. I think there is less appetite to use this agent simply for that reason that we have more effective agents at this time. I agree, [with] bortezomib, I'll occasionally use low teens, like 20% response rate. Response rates are not durable, so I have used it very sporadically for MCL, and in general, we have not been particularly pleased with the results except VR-CAP (rituximab, cyclophosphamide, doxorubicin, prednisone) that Dr. Wang mentioned as one of the frontline regimens, which certainly has viability as a regimen.

Regarding lenalidomide, the lenalidomide-rituximab combinations may be associated with response rates of 30% to 40% in relapsed/refractory MCL. Again, the durability of response is somewhat suboptimal, and the reality is, again, in post-BTK inhibitor setting, it hasn't been extensively studied, and I would go to a BTK inhibitor before lenalidomide any day, whether it's ibrutinib or acalabrutinib. Even in the face of relative contraindications, be that atrial fibrillation or concurrent anticoagulation, I would still choose a BTK inhibitor over lenalidomide. Then, like I said, [with] T-cell enablers, CAR (chimeric antigen receptor) T-cells, [and] bispecifics, I think the role for lenalidomide has been decreasing.

Anthony R. Mato, MD, MSCE: Brian, Michael, anything to add about lenalidomide?

Michael Wang, MD: I was actually the first to publish the rituximab plus lenalidomide therapy in MCL, and then it was studied in other different lymphomas. Initially I thought (it was) the first chemotherapy-free therapy for lymphoma, but later on, we realized that lenalidomide is cytoreductive. Also in the randomized myeloma clinical trials, it clinically, significantly increased the secondary malignancy rate. I feel that it no longer fits the criteria of chemotherapy-free therapy for lenalidomide because of the cytopenia [and] because of the secondary malignancies in randomized trials. It is a semi-chemotherapy. It is especially good when you have achieved greater cytoreduction with some other therapy, or the patient relapsed with a minimal disease. You can still get the patient into good remission that lasts for a long time, so I totally agree with you, Anthony. Lenalidomide usage is decreasing, but it's remained an option for some of the patients during the late relapses.

Transcript has been edited for clarity.