Dr Phillips on the Evolving Treatment Landscape in MCL

Tycel Phillips, MD, associate professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses current and emerging therapeutic treatment strategies for patients with mantle cell lymphoma (MCL).

To date, brexucabtagene autoleucel (brexu-cel; Tecartus) is the only CAR T-cell therapy that is FDA approved for patients with MCL. This agent was approved by the regulatory agency in 2020 for patients with relapsed/refractory disease. This approval was based on findings from the phase 2 ZUMA-2 trial (NCT02601313). In the confirmatory trial, at a median follow-up of 35.6 months, the overall response rate (ORR) with brexu-cel in patients with MCL who had previously received bendamustine- or anthracycline- containing chemotherapy, an anti-CD20 antibody, and a BTK inhibitor was 91% (95% CI, 81.8%-96.7%). Notably, 3% of treatment-emergent adverse effects of interest in this trial occurred during the follow-up period.

Lisocabtagene maraleucel (liso-cel; Breyanzi) is under investigation in patients with relapsed/refractory MCL who have received at least 2 prior lines of therapy in the MCL cohort of the phase 1 TRANSCEND-NHL-001 trial (NCT02631044). Primary findings from this study demonstrated an ORR of 86.5% (95% CI, 76.5%-93.3%; P < .0001). Although these efficacy findings are comparable with those of the ZUMA-2, trial, liso-cel is associated with a more tolerable safety profile than brexu-cel, Phillips says. The data from theTRANSCEND-NHL-001 study may support the potential FDA approval of liso-cel for patients with MCL, Phillips notes.

Bispecific antibodies, such as glofitamab-gxbm (Columvi), are also under investigation for patients with MCL and will are hoped to gain FDA approval, Phillips explains. Furthermore, studies combining bispecific antibodies with classes of drugs such as immunomodulatory agents and BTK inhibitors may support the use of bispecific antibodies in earlier lines of therapy, such as the first- or second-line settings, before CAR T-cell therapy, Phillips emphasizes.

Additionally, in the CAR T-cell therapy arena, therapies targeting different CAR T-cell targets are in development, such as CD20-, ROR1-, and BAFF-R– targeting CARs, Phillips says. CAR T-cell therapies with dual targets are also under evaluation, Phillips notes.

Overall, several novel therapies are under investigation for patients with MCL, and patients have several treatment options, Phillips explains. Future research with these therapies will guide individualized treatment decisions, Phillips concludes.