The complete metabolic response rate was 70% 3 months after infusion.
Axicabtagene ciloleucel (axi-cel) has demonstrated promising efficacy and acceptable safety as a second-line treatment in patients with relapsed/refractory (r/r) aggressive B-cell lymphomas who are ineligible for high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT), according to data from the phase 2 ALYCANTE clinical trial (NCT04531046) presented in an oral session at the 64th American Society of Hematology (ASH) Annual Meeting, held December 10-12, 2022, in New Orleans, Louisiana.
Among the 40 patients treated in the study as of the October 17, 2022, data cut-off, the complete metabolic response (CMR) rate was 70% at 3 months after infusion (95% CI, 53.5-83.4), with a best complete response of 80%. The overall response rate was 75%, with a best response of 92.5%. At the 3-month mark, no patients showed stable disease, 6 patients showed progressive metabolic disease, and 4 patients had died before assessment. At 6 months post-infusion, 60% of patients remain in CMR. The median progression-free survival measured from infusion was 11 months and the median overall survival was not reached.
In terms of safety, 82.5% of patients experienced a grade 3 or greater adverse event (AE), the most common of which were cytopenias. Cytokine release syndrome was experienced by 90% of the patients, with 80% of patients experiencing grade 1-2 cases and 10% of patients experiencing grade 3-4 cases. Immune effector cell-associated neurotoxicity syndrome occurred in 55% of the patients, with 35% of patients experiencing grade 1-2 cases and 20% of patients experiencing grade 3-4 cases. It was additionally noted that 30% of patients were transferred to the intensive care unit, 30% had infections that were grade 3 or greater, and 37.5% experienced cases of prolonged cytopenia of grade 3 or greater. Seven patients in total had died by the time of the data cut-off, with 2 deaths being attributed to lymphoma and 5 deaths attributed to infection AEs, 2 of which were COVID-19 infections.
The ages of the patients treated in the trial ranged from 49 to 81 (median, 68). The group included 28 male patients and 12 female patients. It was noted that 45% of the patients were at least 70 years of age or older. Twenty-one of the patients included in the trial were refractory to first-line treatment, while 19 had relapsed in 12 months or less. Reasons for transplant ineligibility included age (82.5%), Hematopoietic Cell Transplantation-specific Comorbidity score being 3 or greater (30%), and prior ASCT (5%). Bridging therapy with R-GEMOX was received by 92.5% of the patients.
“Importantly, two-thirds of the patients did not respond to bridging therapy, highlighting the fact that these patients were highly chemorefractory,” presenter and first author Roch Houot, MD, PhD, professor of Hematology, head of Hematology Department, University Hospital of Rennes, France, noted in his presentation.
The single-arm, open label, multicenter study treated the patients between April 26, 2021, and January 19, 2022. Patients were able to receive corticosteroids before enrollment, and after leukapheresis patients could receive optional bridging therapy with either R-GEMOX or corticosteroids. Patients received 3 days of conditioning chemotherapy before axi-cel infusion. Exploratory PET-scan and ct DNA analysis was carried out in the pre-treatment and post-treatment periods.
“Preliminary results indicate that early clearance of ct DNA at Day 14 post-infusion was highly predictive of CMR at 3 months,” Houot stated while concluding his presentation. He also noted that the protocol has been "amended to allow an expansion of 22 additional patients (for a total of 62 infused patients) to achieve sufficient power to compare subgroups of patients.”
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