Recent Advancements in Treatment of Mantle Cell Lymphoma and Marginal Zone Lymphoma

Izidore Lossos, MD, University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida, discusses updates for the treatment of patients with mantle cell lymphoma (MLL) and marginal zone lymphoma (MZL) at the 2025 Lymphoma, Leukemia & Myeloma (LL&M) Winter Symposium in Miami, Florida.

Transcript:

Hello, my name is Dr Izidore Lossos. I'm from University of Miami and I'm here at the LL&M Winter Symposium. I will be presenting topics of mantle cell lymphoma and marginal zone lymphoma [featuring] recent updates during the last year. A lot of new publications and presentations appeared, so I will only focus on what, in my opinion, are the major advances.

We will start with the TRIANGLE study. This study was published a year ago in the Lancet Journal and in this ASH meeting there was update on this study still showing advantage of adding ibrutinib to the standard chemotherapy plus maintenance, versus autologous stem cell transplant without this addition of ibrutinib. Interestingly, also potentially showing advantage of eliminating autologous stem cell transplant when you add ibrutinib versus standard aggressive chemotherapy plus autologous stem cell transplant. That was presented in the meeting that it's not only progression-free survival improvement but also advantage in overall survival (OS).

The second presentation that I would like to mention is a study called the ECHO study that analyzed addition of acalabrutinib to [bendamustine and rituximab] (BR) therapy versus currently standard of care BR therapy in elderly patients that are not eligible for stem cell transplant. This study allowed crossover; therefore, we don't know if there will be any difference in overall survivals, probably not, but definitely demonstrated significantly improved progression-free survival. Last week it was approved by the FDA.

The last study on mantle cell lymphoma that I want to mention is a study that analyzed that was done by Alliance A052101 study and that analyzed addition of acalabrutinib in patients with mantle cell lymphoma that are younger and eligible for stem cell transplant to chemotherapy backbone can improve outcomes. There were 3 arms in this study, with first arm 3 cycles of BR plus 3 cycles of acalabrutinib. Second arm was the same regimen but with addition of ibrutinib. The third arm was the same treatment, but with the different way to do it. In this study, the standard arm that was the BR was discontinued early because of lack of efficacy in interim analysis.

There was no difference between the 3 arms with regard to progression-free survival and also with regard to primary end point. The primary end point in this study was interesting. It was PET negativity plus [minimal residual disease] (MRD) negativity, suggesting that most probably we can proceed with addition with acalabrutinib, and this will induce significant responses—and maybe we don't need to add [rituximab and zanubrutinib] (RZ). That until now was quite a standard therapy because the outcomes were not different, and BR therapy with acalabrutinib had fewer side effects.

I'll move to marginal zone lymphoma. On the marginal zone lymphoma, there were a few studies that analyzed novel BTK inhibitors. These studies were small and only provide us initial glimpse on their potential, but to me it seems that it'll not be different from the current BTK inhibitors that we already using or approved for this disease.

The true major advantages, in my opinion, is the addition of bispecific antibodies. One with the use of mosunetuzumab plus or minus revlimid in patients that do not achieve responses. The second study was a study on odronextamab. Both studies demonstrated interesting and high responses, but the follow-up still is short. We will need to wait for longer follow-up. We presented a study on loncastuximab. It was interim analysis, and it reached statistical significance as was predicted and the study is ongoing.

Source:

Lossos I. Updates in Mantle Cell Lymphoma and Marginal Zone Lymphoma. Presented at Lymphoma, Leukemia & Winter Symposium; February 7-9, 2025. Miami, FL.