Lisocabtagene maraleucel in follicular lymphoma: the phase 2 TRANSCEND FL study

Abstract

An unmet need exists for patients with relapsed/refractory (R/R) follicular lymphoma (FL) and high-risk disease features, such as progression of disease within 24 months (POD24) from first-line immunochemotherapy or disease refractory to both CD20-targeting agent and alkylator (double refractory), due to no established standard of care and poor outcomes. Chimeric antigen receptor (CAR) T cell therapy is an option in R/R FL after two or more lines of prior systemic therapy, but there is no consensus on its optimal timing in the disease course of FL, and there are no data in second-line (2L) treatment of patients with high-risk features. Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, 4-1BB CAR T cell product. The phase 2 TRANSCEND FL study evaluated liso-cel in patients with R/R FL, including 2L patients who all had POD24 from diagnosis after treatment with anti-CD20 antibody and alkylator ≤6 months of FL diagnosis and/or met modified Groupe d'Etude des Lymphomes Folliculaires criteria. Primary/key secondary endpoints were independent review committee-assessed overall response rate (ORR)/complete response (CR) rate. At data cutoff, 130 patients had received liso-cel (median follow-up, 18.9 months). Primary/key secondary endpoints were met. In third-line or later FL (n = 101), ORR was 97% (95% confidence interval (CI): 91.6‒99.4), and CR rate was 94% (95% CI: 87.5‒97.8). In 2L FL (n = 23), ORR was 96% (95% CI: 78.1‒99.9); all responders achieved CR. Cytokine release syndrome occurred in 58% of patients (grade ≥3, 1%); neurological events occurred in 15% of patients (grade ≥3, 2%). Liso-cel demonstrated efficacy and safety in patients with R/R FL, including high-risk 2L FL. ClinicalTrials.gov identifier: NCT04245839 .

Fig. 1. CONSORT diagram for patients with 3L+ FL and patients with high-risk 2L FL.

^aThe high-risk 2L FL cohort included patients with POD24 from diagnosis and/or who met mGELF criteria. ^bOne patient had history of transformed FL, and one patient had PET-negative disease at pre-treatment assessment. ^cReached CR after bridging therapy per investigator assessment and had PET-negative disease at pre-treatment assessment. ^dNon-conforming product was defined as any product wherein one of the CD8 or CD4 cell components did not meet one of the requirements to be considered liso-cel but was considered appropriate for infusion.

Fig. 2. ORR by best overall response per IRC assessment.

^aOne-sided P value using exact binomial test (H₀ of ORR ≤ 60%; H₀ of CR rate ≤ 30%). ^bOne-sided P value using exact binomial test (H₀ of ORR ≤ 50%; H₀ of CR rate ≤ 19%). ^cNot statistically tested (descriptive). H₀, null hypothesis; PR, partial response; SD, stable disease.

Fig. 3. Kaplan–Meier curves for DOR, PFS and OS (efficacy set).

Kaplan–Meier data are presented as median (95% CI). Median follow-up was calculated using the reverse Kaplan–Meier method. ^aDOR was defined as time from first response to PD or death from any cause. Median follow-up for DOR in 2L+ was 16.7 months (95% CI: 16.2‒16.9). ^bPFS was defined as time from liso-cel infusion to PD or death from any cause. Median follow-up for PFS in 2L+ was 17.6 months (95% CI: 17.1‒17.8). ^cOS was defined as time from liso-cel infusion to time of death from any cause. Median follow-up for OS in 2L+ was 17.9 months (95% CI: 17.45‒18.0). A total of 90% of patients in the efficacy set were censored from the OS analysis at data cutoff. mo, months.