CAR-T Shows ‘Superiority’ to Allogeneic HSCT as Salvage Therapy for LBCL

Axicabtagene ciloleucel showed “superiority” over allogeneic hematopoietic stem cell transplantation (HSCT) as a salvage therapy for patients with large B-cell lymphoma (LBCL) with treatment failure after at least two lines of systemic therapy, according to long-term follow-up results of an intention-to-treat analysis.

Peter Dreger, MD, of the University of Heidelberg in Germany, presented the results of the research comparing chimeric antigen receptor (CAR) T-cell therapy and allogeneic HSCT during the European Society for Blood and Marrow Transplantation-European Hematology Association Fifth European CAR T-Cell Meeting.

Dr. Dreger and colleagues published in 2020 an intention-to-treat analysis “suggesting that CD19-directed CAR-Ts might be superior to [allogeneic HSCT] when used for rescuing patients with relapsed/refractory LBCL beyond the second systemic treatment line.”

“However, the CAR-T sample in that study was relatively small and follow-up relatively short,” Dr. Dreger and colleagues wrote. “Here we present an update along with a separate confirmatory analysis using all consecutive patients with intent to [receive axicabtagene ciloleucel] until December 2021 as comparators.”

The study included all patients who were referred to the investigators’ institution with relapsed or refractory LBCL, had at least two prior lines of therapy, and a tumor board recommendation for standard-of-care CAR-T between July 2018 and December 2021. Dr. Dreger and colleagues retrospectively compared these patients to all consecutive patients with relapsed/refractory LBCL who had an allogeneic donor search initiated between 2004 and 2020.

The study’s main endpoints were the proportion of patients proceeding to cellular immunotherapy, overall survival (OS) from indication, and outcomes after cellular immunotherapy.

For the primary analysis, the investigators re-evaluated the 41 patients who intended to receive CAR-T, and the 39 patients who intended to receive allogeneic HSCT. At the cellular therapy indication, both cohorts were “comparable” for age, gender, comorbidities, performance status, secondary International Prognostic Index, and pretreatment lines, according to Dr. Dreger and colleagues.

However, patients who intended to receive CAR-T had a shorter median time from diagnosis (12 months) than those who intended to receive allogeneic HSCT (17 months; P=.041). Furthermore, 10% of patients who intended to receive CAR-T had transformed follicular lymphoma, while 36% of those who intended to receive allogeneic HSCT had transformed follicular lymphoma. Less than one-quarter of patients who intended to receive CAR-T (22%) had prior autologous HSCT failure, while 59% of those who intended to receive allogeneic HSCT had prior autologous HSCT failure.

The median follow-up time for survivors, measured from cellular immunotherapy indication, was 37 months for the CAR-T cohort and was 57 months for the allogeneic HSCT cohort.

The estimated 36-month OS rate was 27% in the CAR-T cohort, while it was 15% in the allogeneic HSCT cohort, when measured from cellular immunotherapy indication (P=.079). When measured from cellular immunotherapy administration, the estimated 36-month OS rate was 37% in the CAR-T cohort and 27% in the allogeneic HSCT cohort (P=.0996).

There were no significant differences in progression-free survival or relapse incidence 36 months after cellular immunotherapy. However, the nonrelapse mortality rate was 10% in the CAR-T cohort, significantly lower than the 36% nonrelapse mortality rate in the allogeneic HSCT cohort (P=.018).

In the confirmatory analysis, all 61 consecutive patients with relapsed/refractory LBCL who had a tumor board decision recommending axicabtagene ciloleucel between July 2018 and December 2021 were included in the CAR-T cohort. Of those 61 patients, 77% proceeded to re-infusion.

The estimated 24-month OS rate was 30% in the CAR-T cohort, while it was 15% in the allogeneic HSCT cohort when measured from the cellular immunotherapy indication (P=.021). When measured from cellular immunotherapy administration, the estimated 24-month OS rate was 40% in the CAR-T cohort and was 27% in the allogeneic HSCT cohort (P=.031).

The estimated 24-month nonrelapse mortality was significantly lower in the CAR-T cohort (9%) than in the allogeneic HSCT cohort (36%; P=.031), but there was no significant difference in the other endpoints.

“In line with the original analysis, long-term follow-up and sample size extension confirm [axicabtagene ciloleucel’s] superiority over [allogeneic HSCT] when used as salvage treatment in patients with LBCL having failed at least two lines of systemic therapy,” Dr. Dreger and colleagues concluded. “However, the limitations of this study, such as the small sample size and the long inclusion period of the [allogeneic HSCT] cohort, have to be taken into account.”

Reference

Krämer I, Dietrich S, Schubert ML, et al. CAR T-cells vs allogeneic transplantation in relapsed large B-cell lymphoma. Presented at the European Society for Blood and Marrow Transplantation-European Hematology Association Fifth European CAR-T cell Meeting; February 9-11, 2023; Rotterdam, Netherlands.