Liso-Cel Associated With Improved Benefit in Earlier Lines of Therapy in R/R Mantle Cell Lymphoma

Clinically meaningful activity was found across all subgroups of patients with relapsed/refractory mantle cell lymphoma (MCL) in a posthoc subgroup analysis of the phase 1 TRANSCEND NHL 001 trial (NCT02631044), which evaluated systemic therapy lines given prior to treatment with lisocabtagene maraleucel (liso-cel; Breyanzi) during the study. Findings were presented at the 2024 EHA Congress.

Patients who received fewer than 5 prior lines of therapy had numerically higher median duration of response (DOR), progression-free survival (PFS), and overall survival (OS). After 5 or more prior lines of therapy, the median DOR was 6.7 months (95% CI, 2.4-15.8), the median PFS was 7.4 months (95% CI, 3.3-12.3), and the median OS was 13.5 months (95% CI, 9.5-17.1). The respective values for patients with 3 or 4 prior lines were 17.5 months (95% CI, 3.3-not reached [NR]), 16.6 months (95% CI, 2.6-NR), and 18.4 months (95% CI, 6.7-NR).

For patients who had disease that was not refractory, the median DOR was 24.0 months (95% CI, 7.6-NR) vs 5.3 months (95% CI, 2.3-15.8) in those who had refractory disease. The median PFS was 24.0 months (95% CI, 8.6-NR) vs 6.1 months (95% CI, 3.1-16.5), and the median OS was 36.3 months (95% CI, 15.3-NR) vs 11.1 months (95% CI, 6.1-17.1).

“The better efficacy and safety profile observed in patients with [relapsed/refractory MCL] who received [fewer than 5] prior lines of therapy and those with disease not refractory to prior BTKi support the use of liso-cel in earlier lines of therapy,” the authors wrote in the poster.

Overall, 104 patients received leukapheresis, and 88 received liso-cel with a median study follow-up of 16.1 months. During lymphodepletion, patients were given fludarabine at 30 mg/m² and cyclophosphamide at 300 mg/m² every 3 days. Liso-cel was given 2 to 7 days after, and at day 29, the first disease assessment was completed. Six patients received 50 x 10⁶ CAR T cells, and 82 were given 100 x 10⁶ CAR T cells, which is the recommended dose.

In the overall population, 69% of patients had refractory disease, 53% were refractory to any BTKi, and the median time from diagnosis to liso-cel treatment was 63.75 months. Those who were refractory had previously received ibrutinib (Imbruvica; 54%; n = 35/65), acalabrutinib (Calquence; 52%; n = 15/29), pirtobrutinib (Jaypirca; 50%; n = 3/6), and zanubrutinib (Brukinsa; 50%; n = 1/2). Overall, 57% (n = 47/83) were refractory to any prior BTKi.

For patients who received 5 or more prior lines of therapy, the overall response rate (ORR) was 81% (95% CI, 60.6%-93.4%), and the complete response (CR) rate was 65% (95% CI, 44.3%-82.8%). Among patients with 3 or prior lines of therapy, the ORR and CR rate, respectively, was 86% (95% CI, 68.3%-96.1%) and 72% (95% CI, 52.8%-87.3%).

For those who were not refractory, the ORR was 91% (95% CI, 76.9%-98.2%), and the CR rate was 80% (95% CI, 63.1%-91.6%). For those who were refractory, the ORR was 76% (95% CI, 60.5%-87.1%), and the CR rate was 64% (95% CI, 48.8%-78.1%).

In those who were given 5 or more prior lines of therapy, 96% of patients had grade 3 or higher treatment-emergent adverse effects (TEAEs) compared with 84% of those with 3 or 4 prior lines. The most common toxicities in each group included anemia (65% vs 29%), neutropenia (58% vs 45%), and thrombocytopenia (42% vs 16%).

For those with non-refractory vs refractory disease, the most common grade 3 or higher TEAEs included neutropenia (53% vs 57%), anemia (33% vs 45%), and thrombocytopenia (22% vs 28%).

TEAEs of special interest in those treated with 5 or more prior lines of therapy and patients who received 3 or 4 prior lines, respectively, included cytokine release syndrome (CRS; 69% vs 68%) and prolonged cytopenia (50% vs 32%). Additionally, grade 3 or higher infections affected 19% vs 13%, and tumor lysis syndrome occurred in 4% vs 3%.

For those with non-refractory and refractory disease, CRS occurred in 58% of patients vs 64%, and prolonged cytopenia in 33% vs 45%. Across the prespecified cohorts, grade 3 or higher infections occurred in 11% vs 19%, and tumor lysis syndrome in 3% vs 2%.

In May 2024, the FDA approved liso-cel for this population based on results from the full efficacy analysis.2,3 Overall, 85.3% (95% CI, 74.6%-92.7%) of patients responded to treatment with liso-cel; the CR rate was 67.6% (95% CI, 55.2%-78.5%).

References

1. Palomba ML, Siddiqi T, Gordon LI, et al. Subgroup analyses in patients with R/R MCL treated with lisocabtagene maraleucel by prior lines of therapy and response to Bruton tyrosine kinase inhibitor from the TRANSCEND NHL 001 MCL cohort. Presented at the European Hematology Association (EHA) 2024 Hybrid Congress; Madrid, Spain; June 13-16, 2024. P1126.
2. 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 14, 2024. https://tinyurl.com/43h4juen
3. 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