Liso-Cel Delivers Deep, Durable Responses in R/R MCL

Lymphomas: © David A Litman - stock.adobe.com

The chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (liso-cel; Breyanzi) delivered a high complete response (CR) rate and showed a relatively low incidence of grade 3 or higher cytokine release syndrome (CRS) or neurological events (NEs) in patients with heavily pretreated relapsed or refractory (R/R) mantle cell lymphoma (MCL).¹

Findings from the MCL cohort of the phase 1 TRANSCEND NHL 001 study (NCT02631044) were published in the Journal of Clinical Oncology. A total of 88 patients who received liso-cel. At a median follow-up of 16.1 months (range, 0.4-60.5), the overall response rate (ORR) was 83.1% (95% CI, 73.3%-90.5%) and the CR rate was 72.3% (95% CI, 61.4%-81.6%). Further, the median duration of response (DOR) was 15.7 months (95% CI, 6.2-24.0), and progression-free survival (PFS) was 15.3 months (95% CI, 6.6-24.9).

CRS was observed in 61% of patients (n = 54), with only 1% of patients (n = 1) experiencing grade 4 CRS and no patients experiencing grade 3 or 5 CRS. NEs were reported in 31% of patients, with 9% of patients experiencing grade 3 or 5 NEs.

“There is an urgent need for CAR T-cell therapy options with low incidence of CRS, NEs, and infections. With a favorable benefit/risk profile and consistent responses in high-risk patient populations (eg, high Ki-67 proliferation index, TP53 mutations, blastoid morphology, and secondary CNS lymphoma), liso-cel may help to address this unmet clinical need,” study authors wrote.

Regarding patient demographics, 73% of patients were aged 65 years and older, and the median age was 68.5 years (range, 36-86). The median number of previous lines of therapy was 3 (range, 1-11). Refractory disease was reported in 69% of patients (n = 61), with 53% of patients (n = 36) refractory to treatment with a Bruton tyrosine kinase (BTK) inhibitor. TP53 mutations were observed in 23% of patients (n = 20), while 31% of patients (n = 27) had blastoid morphology.

The primary end points of the TRANSCEND NHL 001 trial are eaincidence of adverse events (AEs) , probability of dose-limiting toxicities, and ORR. CR rate is the key secondary end point, with other secondary end points including DOR, PFS, overall survival, cellular kinetic parameters, health-related quality of life, and hospitalizations.

Regarding safety, 86% (n = 76) of patients experienced grade ≥ 3 treatment-emergent AEs (TEAEs), andthe most common were neutropenia (56%), anemia (37.5%), and thrombocytopenia (25%). Grade ≥ 3 infections were reported in 15% of patients, while prolonged cytopenia was reported in 25% of patients. Serious TEAEs were observed in 53% (n = 47), and 39% of patients (n = 34) had serious TEAEs that were considered related to liso-cel.

“CAR T-cell therapies continue to evolve in R/R MCL. Both brexucabtagene autoleucel [brexu-cel; Tecartus] and liso-cel target CD19; however, alternative targets are being explored such as BAFF-R and ROR1. Additionally, bispecific antibodies are emerging as a new therapeutic modality, including glofitamab [Columvi}. Studies are still ongoing, and the clinical activity of these therapies has not yet been fully established,” study authors wrote.

“There's nothing that can cure relapsed/refractory MCL outside of CAR T. There's a lot of great drugs out there and I'm very interested in them,” Andre Goy, MD, physician-in-chief, Hackensack Meridian Health Oncology Care Transformation Services, and chairman, chief physician officer, chief, Lymphoma Division, John Theurer Cancer Center, Hackensack University Medical Center, said in an interview with Targeted Oncology^TM. “There was a lot of concern in the beginning with CAR T toxicity. We have learned how to manage and are pre-emptive with toxicity. I haven't seen a patient in the [intensive care unit] with CAR T in a long time. Now if we refer patients earlier, they have a 1 and done treatment and we should all go for this.”

REFERENCES:

1. 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. Published online December 10, 2023. doi:10.1200/JCO.23.02214