S223: real-world early outcomes of axicabtagene ciloleucel for relapsed or refractory follicular lymphoma

Background: Axicabtagene ciloleucel (axi-cel) is an autologous chimeric antigen receptor (CAR) T-cell therapy approved for adult patients with relapsed or refractory (R/R) follicular lymphoma after ≥2 lines of systemic therapy. In the primary analysis of the pivotal ZUMA-5 trial, 94% of patients who received axi-cel to treat R/R follicular lymphoma achieved an objective response, with a 79% complete response rate (Jacobson et al. Lancet Oncol. 2022). Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in 6% and 15% of patients, respectively. Aims: Here, we present the real-world outcomes of patients receiving axi-cel for R/R follicular lymphoma, including those who would have been ineligible for ZUMA-5. Methods: A total of 230 patients from 72 US centers receiving first axi-cel for R/R follicular lymphoma in the real-world setting between March 2021 and October 2022 were identified from the Center for International Blood and Marrow Transplant Research registry. The following patients were excluded: no consent, prior non-transplant cellular therapy, and follicular lymphoma Grade 3b or 3a/3b unspecified. Of the 230 patients, 151 patients had post-infusion assessments and were included in the analysis of outcomes. Effectiveness outcomes were overall response rate, complete response rate, duration of response, progression-free survival and overall survival. Adverse events included CRS, immune effector cell-associated neurotoxicity syndrome (ICANS) and prolonged cytopenia. Results: Of the 230 patients, median age was 62 years and 60% were male. Prior to infusion, 98% had an ECOG performance score of 0-1, 33% had elevated LDH, and 66% were chemo-resistant. Clinically significant comorbidities were present in 74% of the patients. Ninety-two patients (40%) would have been ineligible for ZUMA-5, mainly due to comorbidities. Patients had a median of 4 (range 1-13) lines of prior therapy including 14% who also underwent prior autologous stem cell transplantation. Median time from leukapheresis to infusion was 28 days (interquartile range, 26-34). 9% of patients received bridging therapy. Outcomes were analyzed among the 151 patients with follow-up (median 6.2 months). Objective response rate and complete response rates were 93% (95% CI 88-97%) and 84% (95% CI 77-89%), respectively. Estimated progression-free survival and overall survival at 6 months were 88% (95% CI 81-92%) and 96% (95% CI 91-98%), respectively. Grade ≥3 CRS (ASTCT consensus) and ICANS (ASTCT consensus) occurred in 2% (95% CI 0-6%) and 13% (95% CI 8-19%) of patients, respectively. Median cumulative incidence estimate for CRS resolution was 5 days; for ICANS resolution, 4 days. Among patients alive at Day 30 (n=150), 11% experienced prolonged cytopenia (4% neutropenia, 9% thrombocytopenia). Progression-free survival and overall survival at 6 months were comparable regardless of ZUMA-5 eligibility, while patients eligible for ZUMA-5 had fewer Grade ≥3 ICANS (10% vs 16%) and more rapid ICANS resolution (92% vs 71% resolved within 2 weeks). Patients aged ≥65 vs <65 years had comparable effectiveness and safety profiles. Summary/Conclusion: This is the first report on axi-cel to treat R/R follicular lymphoma in real-world settings. Despite a broader patient population, early results demonstrate effectiveness and safety profiles consistent with those observed in the ZUMA-5 trial. The intent is to present findings from an updated dataset with longer follow-up. Overall, these findings support the continued broad use of axi-cel to treat R/R follicular lymphoma. Keywords: Follicular lymphoma, Real world data, CD19, CAR-T