Liso-cel Effective in Patients with Relapsed or Refractory MCL with High-risk Disease Features

Lisocabtagene maraleucel (liso-cel) demonstrated clinically meaningful efficacy across subgroups of patients with relapsed or refractory mantle cell lymphoma (MCL) with high-risk disease features such as high proliferation index (Ki-67 ≥30%), TP53 mutation, blastoid morphology, and secondary central nervous system (CNS) lymphoma, according to a recent study.

The study, led by Maria Lia Palomba, MD, of Memorial Sloan Kettering Cancer Center in New York, included patients from the MCL cohort of the phase I TRANSCEND NHL 001 study. Patients had positron emission tomography–positive relapsed or refractory MCL after two or more lines of previous therapy, including a Bruton tyrosine kinase inhibitor, alkylating agent, and CD20-targeted agent. Eighty-eight of 104 patients received liso-cel at a target dose of 50 × 10⁶ or 100 × 10⁶ chimeric antigen receptor T cells after lymphodepleting chemotherapy.

Among those treated with liso-cel, 66 (75%) had Ki-67 ≥30% and 15 (17%) had Ki-67 <30%; 20 (23%) had a TP53 mutation present and 34 (39%) did not; and 27 (31%) had blastoid morphology and 48 (55%) did not. Of seven (8%) patients who had secondary CNS lymphoma, five had refractory disease, five had Ki-67 ≥30%, and one each had TP53 mutation and blastoid morphology.

The primary endpoints were treatment-emergent adverse events and overall response rate (ORR), and secondary endpoints included complete response (CR) rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Response rates, PFS, and OS across subgroups were consistent with the overall population, with high ORR and CR rates that were durable and high PFS and OS.

Patients with TP53 mutation had a lower median DOR compared with the overall population (6.2 months vs 15.7 months, respectively), yet patients with TP53 mutation who achieved CR had durable responses. Response rates were high (86% ORR; 71% CR rate) among the seven patients with secondary CNS lymphoma.

Safety outcomes across subgroups were also generally consistent with the overall population, and most cases of cytokine release syndrome and neurological events were low grade.

Reference

Palomba M, Siddiqi T, Gordon L, et al. Lisocabtagene maraleucel (liso-cel) in patients (pts) with R/R MCL: subgroup analyses in pts with high-risk disease features from the MCL cohort of the TRANSCEND NHL 001 study. Abstract #3505. Presented at the 65th ASH Annual Meeting and Exposition; December 9-12, 2023; San Diego, California.