Redefining Frontline Therapy for Mantle Cell Lymphoma

Peter Martin, MD, discussed the evolving frontline treatment landscape for patients who have fitness or transplant eligibility with mantle cell lymphoma (MCL).

He addressed the pivotal question of whether autologous stem cell transplant remains a necessary component of initial therapy, particularly considering emerging data from the phase 3 TRIANGLE trial (NCT02858258). Martin also explored the potential for novel agents to supplant traditional chemotherapy, drawing parallels to established regimens in chronic lymphocytic leukemia (CLL). Overall, he has a positive perspective on how the integration of Bruton tyrosine kinase (BTK) inhibitors and other innovative therapies is reshaping the standard of care for MCL.

Martin is a professor of medicine and chief of the Lymphoma Program at Weill Cornell Medicine.

Transcript:

The first question that comes [to mind] is, what is the role of autologous stem cell transplant? That’s still, to some degree, debatable. The TRIANGLE trial that was reported by the European Mantle Cell Lymphoma Network preliminarily suggests that autologous stem cell transplant may not be necessary in younger patients who are treated with an intensive induction [therapy] in combination with a BTK inhibitor, with maintenance of a BTK inhibitor and rituximab [Rituxan]. There may be some patients who still benefit from an autologous stem cell transplant. There was an unexpected trend toward improved outcomes in [patients] with the higher-risk version of mantle cell lymphoma, which is contrary to what we would normally expect. Is there a role for stem cell transplant or not? For a subset of [patients] with high-risk mantle cell lymphoma, potentially.

The question that follows is, what are the subsequent lines of therapy that we’re using? Is it possible that earlier use of CAR [chimeric antigen receptor] T cells or bispecific antibodies, for example, might be more appropriate than a superintensive strategy that then makes a second-line therapy more difficult? They’re good questions for the future.

Another question for the future will be, is there a role for chemotherapy at all? Outcomes with chemotherapy and BTK inhibitors combined in these [patients who are] younger and fitter are excellent. Is it possible that some [patients] don’t need chemotherapy? That may be true. We’ve seen a number of phase 1 and phase 2 trials that have suggested that these nontraditional cytotoxic chemotherapy-containing regimens can be very successful. We’ve seen in an older population that a nonchemotherapy regimen can be as good as a chemotherapy regimen, depending on how you define good. There’s a scenario where these nonchemotherapy regimens may replace traditional cytotoxic chemotherapy in some [patients] in the near future, and we’ve seen this already with CLL. We’re maybe 5 or 10 years behind in MCL compared with CLL, but the playbook is already there.

Reference

Dreyling M, Doorduijn J, Giné E, et al. Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE): a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network. Lancet. 2024;403(10441):2293-2306. doi:10.1016/S0140-6736(24)00184-3