A “sandwich” strategy of sequential CAR T-cell therapy + auto-HSCT for Ph-negative B-ALL: Phase II findings

Results from a phase II trial (NCT05470777) investigating a “sandwich” strategy combining sequential CD22/CD19 chimeric antigen receptor (CAR) T-cell therapy with autologous hematopoietic stem cell transplantation (auto-HSCT) in 37 adolescents and young adults (AYA) and adult patients with Philadelphia chromosome-negative (Ph-negative) B-cell acute lymphoblastic leukemia (B-ALL) who were ineligible or declined allogeneic HSCT were published by Qian et al. in Cancer. The primary endpoint was overall survival (OS), and the secondary endpoint was leukemia-free survival (LFS).

Key data: At a median follow-up of 28 months, all 35 patients who completed sandwich strategy therapy survived, with overall 2-year OS and LFS rates of 97% (95% confidence interval [CI], 90–100%) and 72% (95% CI, 58–90%), respectively. After second CAR T-cell infusion, 93% of patients with NGS testing (n = 27) achieved next-generation sequencing (NGS)-based measurable residual disease (MRD)-negative complete remission (CR), with 80% and 74% of patients with NGS testing maintaining continuous multiparameter flow cytometry (MFC) MRD negativity and NGS-MRD negativity, respectively, during follow-up. No cases of immune effector cell–associated neurotoxicity syndrome (ICANS) or severe cytokine release syndrome (CRS) were observed.

Key learning: The CD22/CD19 CAR T-cell and auto-HSCT sandwich strategy represents a promising approach for the treatment of Ph-negative B-ALL in AYA and adult patients, offering improved OS and comparable LFS vs allogeneic HSCT, while avoiding graft-versus-host disease (GvHD) complications.