AXICABTAGENE CILOLEUCEL AS SECOND‐LINE THERAPY FOR LARGE B‐CELL LYMPHOMA IN TRANSPLANT‐INELIGIBLE PATIENTS: FINAL ANALYSIS OF ALYCANTE, A PHASE 2 LYSA STUDY (2023)

Introduction: Patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) after first-line treatment who are unable to undergo high-dose chemotherapy (HDCT) and hematopoietic stem cell transplantation (HSCT) have poor outcomes and limited treatment options. In the ZUMA-7 study, Axicabtagene ciloleucel (axi-cel) demonstrated superior efficacy over standard of care (SOC) as second-line therapy in patients intended for transplant (Locke et al. NEJM, 2022). The objective of the open-label, phase 2, ALYCANTE study (NCT04531046) was to evaluate the efficacy and safety of axi-cel in patients with R/R LBCL after 1 prior line of therapy not intended for HDCT/HSCT owing to age and/or comorbidities. Methods: Eligible patients were adults with R/R LBCL that was refractory to or had relapsed no more than 12 months after first-line chemoimmunotherapy and who were not deemed candidates for HDCT/HSCT based on physician’s assessment and at least one of the following criteria: age ≥65 years; age ≥18 years and Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) score ≥3; or age ≥18 years and prior ASCT (as 1st line consolidation). The primary endpoint was the complete metabolic response (CMR) at 3 months from axi-cel infusion based on investigator assessment. The protocol was amended to allow an expansion of 22 additional patients for subgroup comparisons. Results: At the time of data cut-off, 40 patients (out of 62 infused patients) could be analyzed for the primary endpoint. Median on-study follow-up was 10 months. Median age was 68 years (range, 49–81; 45% ≥70 years), 30% had HCT-CI score ≥3, and 52.5% were refractory to first-line treatment. Overall, 37 patients (92.5%) received bridging chemotherapy (R-GEMOX). Twenty-seven patients (67.5%) were refractory to bridging therapy. The study met its primary endpoint with a CMR at 3 months of 70% versus 12% expected with SOC based on historical controls (Cazelles et al. Leukemia & Lymphoma, 2021). Best OR and CR rates were 92.5% and 80%, respectively. Median PFS was 11 months and median OS was not reached. CRS occurred in 90% of patients, including 10% of grade 3–4. ICANS occurred in 55% of patients, including 20% of grade 3–4. Twelve patients (30%) were admitted to ICU. Seven patients died: 2 due to lymphoma and 5 due to fatal infections. Early evaluation of response showed that 64.7% (22/34) and 44.4% (16/36) of patients had a negative PET-CT and an undetectable ctDNA at day 14 post axi-cel infusion, respectively. Conclusions: In the ALYCANTE study, axi-cel as second-line treatment in patients with LBCL who were not deemed candidates for HDCT/HSCT appears feasible and induces high response rates. The final analysis with 22 additional patients (n = 62 vs. 40 patients at current cut-off) and a longer follow-up will be presented at the meeting, including subgroup analysis. The research was funded by: Kite/Gilead Keywords: aggressive B-cell non-Hodgkin lymphoma, cellular therapies Conflicts of interests pertinent to the abstract R. Houot Consultant or advisory role: Kite/Gilead, Novartis, Bristol-Myers Squibb/Celgene, ADC Therapeutics, Incyte and Miltenyi Honoraria: Kite/Gilead, Novartis, Incyte, Janssen, MSD, Takeda and Roche E. Bachy Honoraria: Kite/Gilead F. Gros Honoraria: Kite/Gilead L. Oberic Honoraria: Kite/Gilead P. Feugier Honoraria: Kite/Gilead F. Jardin Honoraria: Kite/Gilead G. Brisou Honoraria: Kite/Gilead