FDA Approval Alert: Liso-Cel in Relapsed/Refractory Mantle Cell Lymphoma

In May 2024, lisocabtagene maraleucel (liso-cel; Breyanzi) was approved by the FDA for patients with relapsed/refractory mantle cell lymphoma (MCL) who have received 2 prior lines of systemic therapy including a Bruton tyrosine kinase inhibitor (BTKi).¹ Data from the approval were based on results from the phase 1 TRANSCEND NHL 001 trial (NCT02631044).²

Stats from the TRANSCEND trial.

Most notable was the objective response rate (ORR) of 85.3% (95% CI, 74.6%-92.7%) observed in 83 patients. The complete response (CR) rate was 67.6% (95% CI, 55.2%-78.5%). The median follow-up was 22.8 months (95% CI, 16.7%-23.0%), and the median duration of response was 15.7 months (95% CI, 6.2-24.0)

The progression-free survival was 15.3 months (95% CI, 6.6-24.9), and the overall survival (OS) was 18.2 months (95% CI, 12.9-36.3). For patients who achieved a CR, the median OS was 36.3 months (95% CI, 15.7-not reached).

ONCOLOGY spoke with Michael Wang, MD, Puddin Clarke Endowed Professor in the Lymphoma Service at The University of Texas MD Anderson Cancer Center, and lead author of the TRANSCEND trial, regarding the approval and how it will be used in the space.

Q / What were the results that led to the approval of liso-cel in patients with relapsed/refractory MCL?

Wang / This approval was exciting, not only because the ORR was high at around 85%. The CR was also high at 67%. Most importantly, the toxicities are not as bad as [previously reported]. Low rates of cytokine release syndrome [CRS; were observed], and low rates of neurotoxicity, making this [agent] a [viable option] for patients who are older and [frail]. Patients who are older and [frail] are those who cannot tolerate intensive CAR T-cell therapy like brexucabtagene autoleucel [brexu-cel; Tecartus] and could be considered for liso-cel therapy. I think this is a great addition to the CAR T-cell therapy options that our patients with MCL have.

Q / Were there any significant adverse effects (AEs) experienced during the trial?

Wang / For liso-cel, the CRS was grade 3/4 and it was low, about 1% to 3%. The neurotoxicity was grade 3/4 and was also low, about 9%. Those numbers are even lower than some of the bispecific antibody-induced CRS and, and neurotoxicities. This is a milder form of CAR T-cell therapy because the CAR T-cell therapy utilizes 4-1BB as a costimulator instead of a CD28 costimulator. The intensity is not as high, so the CRS and the neurotoxicity are relatively low. It is well tolerated by older patients in this setting.

Q / How does the efficacy compare with that of other agents in the space?

Wang / The ORR was 85% with a CR of 67%. This is the newly approved liso-cel compared with the already approved brexu-cel.³ The brexu-cel ORR was 93% with a CR that was 68%. Although the overall response rate is a little higher, the CR rate is 68% vs 67%. They are very comparable in terms of efficacy, especially in the complete remission rate.

However, the toxicity is very different. Because the costimulation factor is CD28 for brexu-cel, which makes the CRS high, the CRS for grades 3/4 is about 15% and the neurotoxicity in grade 3/4 is about 31%. You cannot compare trial to trial, but we at least put the data into historical context. The CRS for the newly approved liso-cel is less than 3% and neurotoxicity grade 3/4 is also quite low, around or less than 9%.

The newly approved product has good efficacy and a much lower toxicity level, making this liso-cel better tolerated in the older or frail population. The second approval for CAR T-cell therapy is a welcome addition to the CAR T-cell therapy list.

Q / What are the next steps for liso-cel in this population?

Wang / In the future, liso-cel needs to combine with different therapies such as the BTKis. Also, liso-cel could be approved with a new construct in the future to modify the microenvironment and make the CAR T-cell therapy work even better.

References

1. U.S. Food and Drug Administration approves Bristol Myers Squibb’s Breyanzi as a new CAR T cell therapy for relapsed or refractory mantle cell lymphoma. News release. Bristol Myers Squibb. May 30, 2024. Accessed June 13, 2024. https://tinyurl.com/43h4juen
2. Wang M, Siddiqi T, Gordon LI, et al. Lisocabtagene maraleucel in relapsed/refractory mantle cell lymphoma: primary analysis of the mantle cell lymphoma cohort from TRANSCEND NHL 001, a phase I multicenter seamless design study. J Clin Oncol. 2023;42(10):1146-1167. doi:10.1200/JCO.23.02214
3. FDA approves brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma. News release. FDA. July 24, 2020. Updated July 27, 2020. Accessed June 13, 2024. https://shorturl.at/7faCD