Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: a phase 2 trial

Abstract

Axicabtagene ciloleucel (axi-cel) demonstrated superior efficacy compared to standard of care as second-line therapy in patients with high-risk relapsed/refractory (R/R) large B cell lymphoma (LBCL) considered eligible for autologous stem cell transplantation (ASCT); however, in clinical practice, roughly half of patients with R/R LBCL are deemed unsuitable candidates for ASCT. The efficacy of axi-cel remains to be ascertained in transplant-ineligible patients. ALYCANTE, an open-label, phase 2 study, evaluated axi-cel as a second-line therapy in 62 patients with R/R LBCL who were considered ineligible for ASCT. The primary end point was investigator-assessed complete metabolic response at 3 months from the axi-cel infusion. Key secondary end points included progression-free survival, overall survival and safety. The study met its primary end point with a complete metabolic response of 71.0% (95% confidence interval, 58.1-81.8%) at 3 months. With a median follow-up of 12.0 months (range, 2.1-17.9), median progression-free survival was 11.8 months (95% confidence interval, 8.4-not reached) and overall survival was not reached. There was no unexpected toxicity. Grade 3-4 cytokine release syndrome and neurologic events occurred in 8.1% and 14.5% of patients, respectively. These results support axi-cel as second-line therapy in patients with R/R LBCL ineligible for ASCT. ClinicalTrials.gov Identifier: NCT04531046 .

Fig. 1. Patient disposition at the data cutoff date of 19 January 2023.

IMP OOS, investigational medicinal product out of specification.

Fig. 2. Kaplan–Meier estimates of event-free survival from leukapheresis, progression-free survival from axi-cel infusion, overall survival from axi-cel infusion and duration of response.

a–d, Kaplan–Meier estimates of EFS from leukapheresis (a), PFS from axi-cel infusion (b), OS from axi-cel infusion (c) and DOR (d). The blue-shaded areas around the survival curve represent the Hall–Wellner 95% confidence bands. NA, not attained.

Fig. 3. Kaplan–Meier estimates according to age of event-free survival from leukapheresis, progression-free survival from axi-cel infusion, overall survival from axi-cel infusion and duration of response.

a–d, Kaplan–Meier estimates according to age (<70 versus ≥70 years) of EFS from leukapheresis (a), PFS from axi-cel infusion (b), OS from axi-cel infusion (c) and DOR (d).

Extended Data Fig. 1

Study design and overview of study procedures.

Extended Data Fig. 2. Causes of autologous stem cell transplantation (ASCT)-ineligibility in the modified full analysis set (N = 62).

Abbreviation: HCT-CI, hematopoietic cell transplantation-specific comorbidity index.

Extended Data Fig. 3

Metabolic response over time in the modified full analysis set (mFAS) (N = 62).

Extended Data Fig. 4. Forest plot illustrating complete metabolic response (CMR) rates at 3 months by subgroup.

Blue squares denote CMR rates, and error bars indicate 95% two-sided 95% exact Clopper-Pearson confidence intervals (CIs). The overall study population is the modified full analysis set (N = 62), in which CMR at 3 months from the axi-cel infusion was 71.0% (95% CI, 58.1%–81.8%). Abbreviations: HCT-CI, hematopoietic cell transplantation-specific comorbidity index; IPI, international prognostic index; LDH, lactate dehydrogenase; PMD, progressive metabolic disease; PMR, partial metabolic response; SD, stable disease; TMTV, total metabolic tumor volume.