Liso-cel Shows Durable Responses in Mantle Cell and Follicular Lymphoma

Image credit: © AkuAku - Adobe Stock

The chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (liso-cel; Breyanzi) had deep and durable responses in patients with follicular lymphoma (FL) and those with mantle cell lymphoma (MCL), according to findings from 2 separate studies whose results were presented at the 2023 International Conference on Malignant Lymphoma.¹

In the phase 2 TRANSCEND FL (NCT04245839) study, there was an overall response rate (ORR) of 97% (95% CI, 91.6%-99.4%; one-sided P < .0001), and 94% of patients achieved a complete response (CR). The median duration of response (DOR) was not reached at 16.6 months median follow-up. In the MCL cohort of the phase 1 TRANSCEND NHL 001 study (NCT02631044), the ORR was 86.5% (95% CI, 76.5%-93.3%; one-sided P < .0001), and the CR rate was 74.3%.

“In TRANSCEND FL, the overall and complete response rates achieved with liso-cel were very high, and appear mostly durable at 12 months, and, importantly, the safety profile was favorable,” Franck Morschhauser, MD, PhD, lead investigator and Professor of Hematology at Centre Hospitalier Universitaire de Lille, Groupe de Recherche sur les forms Injectables et les Technologies Associées, Lille, France, stated in a press release.

“Liso-cel offers the potential for complete responses with a one-time infusion and a manageable safety profile, representing a potential new treatment option for these patients,” Michael Wang, MD, lead investigator of the TRANSCEND NHL 001 trial and professor, department of lymphoma and myeloma, division of cancer medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, stated in the press release.

The open-label, global single-arm phase 2 TRANSCEND FL trial evaluated 101 patients with relapsed/refractory FL in the third line or later who received liso-cel at a target dose of 100 × 106 CAR-positive viable T cells. At 12 months, 81.9% of patients who responded had an ongoing response. The 12-month progression-free survival (PFS) rate was 80.7%, and the median PFS was not reached at 17.5 months median follow-up.

In terms of safety, which also included second-line patients, 130 patients were evaluable and no new safety signals were observed. The safety profile was manageable and cytokine release syndrome (CRS) of any grade occurred in 58% with grade 3 CRS occurring in only 1%. Neurological adverse events (AEs) of any grade occurred in 15% of patients, 2% of whom had grade 3 toxicity. There were no grade 4 or 5 CRS or neurological events.

TRANSCEND NHL 001 was a single-arm phase 1 dose-finding trial that enrolled adults with relapsed/refractory MCL who had received 2 or more prior lines of therapy including Bruton tyrosine kinase inhibitor, alkylating agent, and CD20-targeted agent. They received liso-cel at a dose of either 50 × 106 or 100 × 106 CAR-positive viable T cells.

In addition to the high ORR and CR rates observed in the 74 patients in the primary efficacy analysis, the median DOR was 15.7 months and the median PFS was 15.3 months.²

In the 88 patients evaluated for safety, liso-cel was well tolerated and no new safety signals were observed. CRS of any grade occurred in 61% and grade 3 or 4 CRS occurred in 1%. Neurological AEs were observed in 31%, 9% of which were grade 3 or 4.

According to the press release from Bristol Myers Squibb, the favorable results of these trials will be discussed with health authorities.¹ Liso-cel is currently indicated in the United States for patients with large B-cell lymphoma who are refractory to first-line chemoimmunotherapy either within 12 months or are not eligible for hematopoietic stem cell transplant, or those who have relapsed/refractory disease after 2 prior lines of systemic therapy.³

_References:

_{1. Bristol Myers Squibb’s BREYANZI (lisocabtagene maraleucel) delivers deep and durable responses in relapsed or refractory follicular lymphoma and mantle cell lymphoma in TRANSCEND clinical trials presented at ICML 2023. Bristol Myers Squibb. News release. June 17, 2023. Accessed June 19, 2023. https://tinyurl.com/3ye3jmtd}

_{2. Wang M, Siddiqi T, Gordon LI, et al. Lisocabtagene maraleucel (liso-cel) in R/R MCL: primary analysis results from the MCL cohort of the single-arm, multicenter, seamless design TRANSCEND NHL 001 study. Hematol Oncol. 2023;41(S2):875-877. doi:10.1002/hon.3196_LBA3}

_{3. Breyanzi. Prescribing information. Bristol Myers Squibb; 2022. Accessed June 19, 2023. https://tinyurl.com/4zv55bwe}