Real-world data of lisocabtagene maraleucel as second line therapy for patients with large B-cell lymphoma: Updated Results of the french descar-T registry by lysa

Abstract

Abstract Introduction: Lisocabtagene maraleucel (liso-cel) has demonstrated superior effectiveness as second-line (2L) therapy compared to standard-of-care chemotherapy in transplant-eligible patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL). In the TRANSFORM trial, 92 patients were randomized to receive liso-cel as 2L treatment, of whom 89 were infused, achieving a complete response (CR) rate of 74% and a median event-free survival of 29.5 months. Here, we present real-world data on liso-cel as 2L therapy for patients with early R/R LBCL treated in France. Study Design and Methods: This analysis aimed to describe patient characteristics, treatment courses, and outcomes for all patients consecutively included in the DESCAR-T French nationwide registry (NCT04328298) since September 2022 and infused with liso-cel through the early access program supported by French authorities. This program included patients with LBCL in early relapses (<1 year) or refractory after first-line treatment, regardless of autologous stem cell transplant (ASCT) eligibility. Results: Between September 2022 and February 2025, liso-cel was ordered for 159 patients and leukapheresis was performed in 143 patients. The first infusion occurred in January 2023. No manufacturing failures were reported. At the data cut-off in February 2025, 127 patients had been infused across 13 centers, 11 were awaiting infusion, and 21 were not treated due to reasons including leukapheresis not being done (n=5), deaths (n=12), disease progression (n=2), physician decision (n=1), and patient decision (n=1). Among the 127 infused patients, 72 (57%) were male, with a median age of 68 years (range 18–86). Most had primary refractory disease (n=79, 62%), good performance status (n=96, 76% ECOG 0–1), stage III–IV disease (n=88, 69%), and elevated LDH (n=63, 50%). Median pick-up to liso-cel delivery (turnaround time) was 42 days (range 25–104), and the median vein-to-vein time was 51 days (range 40–108). One hundred sixteen patients (91%) received bridging therapy, mostly immunochemotherapy (n=100/116, 86%). Among those, 21% achieved CR, 27% partial response (PR), and 36% had progressive disease at the time of lymphodepletion. The median follow-up since CAR-T infusion was 6.2 months (range 0–20). Cytokine release syndrome (CRS) occurred in 61 patients (49%), with only two (<5%) experiencing grade 3–4 CRS. Neurotoxicity grades 1–2 occurred in 11 patients (9%), and only one patient experienced grade 3 neurotoxicity. Four patients (3%) were transferred to intensive care. There were no deaths attributed to CRS or neurotoxicity. Seventeen patients (14%) died, 15 due to lymphoma progression and one due to viral infection. Among 118 evaluable patients, 85 (72%) achieved CR and 21 (18%) achieved PR. Longer follow-up is needed to assess response durability. Conclusion:These preliminary results indicate that liso-cel as 2L treatment for R/R LBCL is feasible and safe in French centers. Although follow-up is still short, early response rates and toxicities are consistent with those seen in the TRANSFORM trial, including CR rates above 70%. Liso-cel exhibits a favorable safety profile, with very few cases of severe CRS or neurotoxicity, less than 5% requiring ICU transfer, and only one death related to infection.