Dr Phillips on Treatment Navigation in R/R Mantle Cell Lymphoma

We [will] continue to hopefully invest in more research to find more options, because at this point, we don’t consider bispecific antibodies or CAR-T cell therapy to be curative in patients with MCL.

Tycel Phillips, MD, an associate professor in the Department of Hematology and Hematopoietic Cell Transplantation in the Division of Lymphoma at City of Hope, discussed considerations for navigating treatment options for relapsed/refractory mantle cell lymphoma (MCL) following covalent BTK inhibitor–based therapy, including novel strategies using cellular and immune therapies.

In the evolving treatment paradigm for relapsed/refractory MCL, emerging strategies continue to shape clinical decision-making, Phillips said. Bispecific antibodies are not currently FDA approved in the MCL setting, and although some agents may be accessible through National Comprehensive Cancer Network–supported pathways, Phillips noted. He added that the integration of these agents into routine practice remains inconsistent, particularly in community oncology settings, where experience with bispecific antibody administration may be limited.

At present, CAR T-cell therapy remains a preferred option for many eligible patients because of its demonstrated ability to induce deeper and more durable remissions compared with currently available alternatives, he said. The noncovalent BTK inhibitor pirtobrutinib (Jaypirca) is viewed as an effective bridging strategy and may provide durable responses in a subset of patients, although long-term disease control is not expected for the majority, necessitating subsequent therapy, Phillips added.

Bispecific antibodies are generating increasing interest because of their favorable logistical profile and potentially lower toxicity burden relative to CAR T-cell therapy, he continued, noting that updated results from a phase 1/2 trial (NCT03075696) evaluating glofitamab-gxgm (Columvi) monotherapy will be presented at the 2026 ASCO Annual Meeting. Unlike the CAR T-cell therapy brexucabtagene autoleucel (Tecartus), which carries known risks of neurologic toxicity, bispecific antibodies may have a more manageable safety profile and do not carry the potential manufacturing delays associated with autologous CAR T-cell therapy production, he said.

If a bispecific antibody gains regulatory approval for MCL, it may move earlier in the treatment algorithm for many patients because of ease of administration and broader accessibility, according to Phillips. Ongoing follow-up will be critical to determine whether these responses are sufficiently durable to position bispecific antibodies alongside CAR T-cell therapy as long-term disease control strategies, Phillips noted.