Promising Advances in the Treatment of Patients With Mantle Cell Lymphoma

At the 2023 Society of Hematologic Oncology (SOHO) annual meeting in Houston, Texas, Michael Wang, MD, MD Anderson Cancer Center, Houston, Texas, speaks on the continually evolving landscape of research and treatment advances for patients with mantle cell lymphoma (MCL). 

Transcript: 

I'm Michael Wang from the MD Anderson Cancer Center. I'm the Puddin Clark endowed professor in the department of lymphoma [and] myeloma division of cancer medicine. At the [Society of Hematologic Oncology] (SOHO) [annual meeting], I shared my presentation [on] the major advances in mantle cell lymphoma. 

First of all, we want to discuss the most recent FDA approval. The most recent FDA approval in January of 2023 was on pirtobrutinib in relapsed mantle cell lymphoma. In that clinical trial, called [the] BRUIN clinical trial, there [are] many subsets on [chronic lymphocytic leukemia] (CLL), Waldenström [macroglobulinemia], large cell lymphoma, and other lymphomas. I focused my presentation on the mantle cell lymphoma data. The mantle cell lymphoma data showed a response rate of 57% in patients with prior exposure [to] combined BTK inhibitors and in patient[s] [who were] BTK previously naive.

For those who never received BTK, covalent BTK inhibitor Jaypirca [pirtobrutinib] induced a response of 85%. This is a very impressive part. The phase 3 clinical trial is ongoing to test the pirtobrutinib with any covalent BTK inhibitor of choice. 

Prior to that, the FDA approved brexucabtagene autoleucel, CD19, [chimeric antigen receptor] (CAR) T-cell therapy. This was approved by the FDA in July of 2020. The overall response rate was 93%, [complete response] (CR) was 69%, and the duration of response was feasible in the most recently presented 3-year follow-up data. Brexucabtagene [autoleucel] is widely used in every major institution where CAR T[-cell therapy] is available to treat relapsed mantle cell lymphoma patients and with good results. 

Prior to that, the major advance was the approval of zanubrutinib in 2019 for relapsed mantle cell lymphoma. The response rate is over 80%, the CR is very impressive, and zanubrutinib is approved, and it's been used in the community because it's an oral drug, as well as in academic centers.

Prior to that, another major advance was the approval of covalent BTK inhibitor acalabrutinib in 2017 for relapsed mantle cell lymphoma. This is also widely used. Even before that was the approval of the first covalent BTK inhibitor, ibrutinib, in 2013. In a subsequent study, the response rate was very high and the CR rate was also high. 

However, the long-term phase 3 clinical trial, the SHINE study, showed that the overall survival between the [bendamustine rituximab] (BR) placebo arm versus the BR plus ibrutinib arm was superimposed. As a result, the covalent BTK inhibitor ibrutinib was [voluntarily] withdrawn from the market (Editor’s note: Specifically, for patients with MCL who have received at least 1 prior therapy as well as patients with marginal zone lymphoma who require systemic therapy and have received at least 1 prior anti–CD20–based therapy.) 

This has brought many changes, [and] is another major event in the field of mantle cell lymphoma. In the future, we are witnessing many other agents coming up, including BTK inhibitor degraders, BCL-2 analogs or BCL-2 inhibitors, venetoclax analogs, and also BCL-XL, CDK-19.

Of course, the other major advance is the emerging bispecific antibodies. Glofitamab has generated very impressive data in relapsed mantle cell lymphoma, and phase 3 clinical trials [are] ongoing. Another subcutaneous bispecific antibody [is] called epcoritamab. 

The trial is also ongoing, so the future of mantle cell lymphoma is bright. Not only have we used all these agents in the relapsed setting, but we have also brought them to the frontline. The studies in the frontline are also ongoing and some of them are already read out. We are making a lot of changes and progress in treating mantle cell lymphoma. Thank you for listening.

Source: 

Wang M. Major Advances in the Fight Against Mantle Cell Lymphoma. Presented at the Society of Hematologic Oncology (SOHO) Annual Meeting; September 6-9; Houston, Texas.