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Axicabtagene Ciloleucel As Second-Line Therapy for Large B-Cell Lymphoma in Transplant-Ineligible Patients: Primary Analysis of Alycante, a Phase 2 Lysa Study

2022; Elsevier BV; Volume: 140; Issue: Supplement 1 Linguagem: Inglês

10.1182/blood-2022-156626

1528-0020

Roch Houot, Emmanuel Bachy, Guillaume Cartron, François‐Xavier Gros, Franck Morschhauser, Lucie Oberic, Thomas Gastinne, Pierre Feugier, Rémy Duléry, Catherine Thiéblemont, Magalie Joris, Francisco Llamas‐Gutierrez, Emmanuel Itti, Cédric Menard, Yassine Al-Tabaa, Clément Bailly, Marie-Hélène Delfau, Camille Laurent, François Lemonnier,

Lymphoma Diagnosis and Treatment

Background 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. Axicabtagene ciloleucel (axi-cel) has recently demonstrated superiority over standard of care (SOC; salvage chemotherapy followed by HDCT/HSCT in responders) as second-line therapy in patients intended for transplant in the phase 3, ZUMA-7 study (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). Patients received lymphodepletion with cyclophosphamide and fludarabine, followed 2 days later by axi-cel infusion at a target dose of 2 × 10^6 CAR T-cells/kg. Cytokine release syndrome (CRS) and neurological events (ICANS) were graded using the ASTCT grading system. The primary endpoint was the complete metabolic response (CMR) at 3 months from axi-cel infusion based on investigator disease assessment. Results Of 43 patients who underwent leukapheresis, 40 received axi-cel. 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 for all patients but one). Twenty-seven patients (67.5%) were refractory to bridging therapy, including 15 patients (37.5%) who experienced disease progression upon bridging therapy. Median on-study follow-up was 6.7 months. The study met its primary endpoint with a CMR at 3 months of 67.5% versus 12% expected with SOC based on historical controls (Cazelles et al, Leukemia & Lymphoma 2021). Objective response (OR) rate at 3 months was 75%. Best OR and CR rates were 92.5% and 77.5%, respectively. CRS were seen in 90% of patients, including 10% of grade 3-4. ICANS were seen in 55% of patients, including 17.5% of grade 3-4. Twelve patients (30%) patients were admitted to ICU. Six patients died: 2 due to lymphoma and 4 due to fatal adverse events (COVID-19, mucormycosis, perineal infection, and sepsis). Grade ≥ 3 prolonged cytopenias (i.e. not resolved on Day 29 after axi-cel infusion) occurred in 14 patients (35%). 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. Additional exploratory analyses are ongoing, including early PET-CT at Day 14 post-infusion and ctDNA monitoring, which will be presented at the meeting. Finally, the protocol was amended to allow an expansion of 20 additional patients (for a total of 60 patients) to achieve sufficient power to compare 2 subgroups of patients based on age (≥ 70 vs < 70 years).