Dr Danilov on Therapeutic Options After BTK Inhibitors in MCL

Alexey Danilov, MD, PhD, associate director, Tino Stephenson Lymphoma Center, professor, Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses treatment developments for patients with mantle cell lymphoma (MCL) who have progressed on BTK inhibitors.

Although CAR T-cell therapies have been shown to be effective in patients with MCL, their curative potential remains to be seen, Danilov says. In 2020, brexucabtagene autoleucel (brexu-cel; Tecartus) was approved by the FDA for adult patients with relapsed/refractory MCL. In addition, findings from the MCL cohort of the phase 1 TRANSCEND NHL 001 trial (NCT02631044) of lisocabtagene maraleucel (liso-cel; Breyanzi) in patients who had relapsed or were refractory to at least 2 prior lines of therapy, including a BTK inhibitor, were presented at the 2023 International Congress on Malignant Lymphoma. In this trial, liso-cel elicited an overall response rate of 86.5% (95% CI, 76.5%-93.3%), including a complete response rate of 74.3% (95% CI, 62.8%-83.8%).

Another development in the relapsed/refractory MCL treatment landscape was the January 2023 FDA approval of the noncovalent BTK inhibitor pirtobrutinib (Jaypirca). Because of pirtobrutinib’s ability to overcome mutations associated with BTK inhibitor resistance, such as BTK C481S, this agent is effective in the post–covalent BTK inhibitor setting, Danilov explains. In the pivotal phase 1/2 BRUIN trial (NCT03740529), 50% (95% CI, 41%-59%) of patients responded to pirtobrutinib, with a median duration of response of 8.3 months (95% CI, 5.7-not evaluable). Moreover, the toxicity profile of this agent was favorable, Danilov notes.

The emerging bispecific antibodies in the field of MCL management include mosunetuzumab-axgb (Lunsumio), which was approved by the FDA in 2022 for patients with relapsed/refractory follicular lymphoma. Furthermore, the bispecific antibodies epcoritamab-bysp (Epkinly) and glofitamab-gxbm (Columvi) are FDA approved for use in patients with diffuse large B-cell lymphoma. Data are maturing regarding the efficacy of glofitamab in patients with relapsed/refractory MCL, Danilov says.

Noncovalent BTK inhibitors and bispecific antibodies are promising novel treatment approaches for patients with MCL, although more mature data are needed to determine their positions in the treatment paradigm alongside CAR T-cell therapies, Danilov concludes.