Reference: August 2026 | Issue 8 | Vol 12 | Page 35
Blinatumomab (BLI), inotuzumab ozogamicin (INO), and CAR T cell therapy have reshaped the treatment of relapsed/refractory (R/R) and minimal residual disease (MRD)-positive (MRD+) Bcell acute lymphoblastic leukaemia (B-ALL) by facilitating transplantation eligibility. Yet, the optimal pre-haematopoietic stem cell transplantation (HSCT) strategy and its influence on post-transplant toxicity and survival remain undefined.
A study presented at EHA 2026 directly compared BLI, INO, and CAR T cell therapy as pre-transplant strategies in a consecutive cohort of patients with R/R or MRD+ B-ALL who proceeded to HSCT following antibody-based immunotherapy (BLI/INO) or CAR T therapy. Patients were stratified by disease status at initiation of bridging therapy (R/R vs MRD+), and then by initial treatment strategy (immunotherapy vs cellular). Patients who failed monotherapy and subsequently received ≥2 lines of cellular or immunotherapy were analysed as a separate multi-line cohort.
A total of 286 patients were included, of whom 149 (52 per cent) were MRD+ and 137 (48 per cent) had active R/R disease before immune or cellular therapy. In the R/R cohort, cellular therapy (n=78) was associated with significantly superior post-HSCT outcomes compared with immunotherapy (n=41), including higher three-year overall survival (90% vs 69%; P=0.022) and disease-free survival (72% vs 48%; P=0.040).
Multivariable analysis confirmed immunotherapy as an independent adverse factor for overall survival (OS), disease-free survival (DFS) and graft-versus-host-disease-free survival (GRFS) in R/R ALL. In the MRD+ cohort, OS and DFS were comparable between cellular therapy (n=49) and immunotherapy (n=79). Both strategies demonstrated superior OS compared with multi-line therapy (n=21). OS with cellular treatment was 86 per cent versus 61 per cent with multi-line therapy (P=0.006), and OS with immunotherapy was 85 per cent versus 61 per cent with multi-line therapy (P<0.001).
In the overall cohort, persistent pre-HSCT MRD on flow cytometry was strongly associated with inferior survival outcomes, including three-year OS (47 per cent vs 86 per cent; P<0.001), DFS (29 per cent vs 70 per cent; P=0.001), GRFS (31 per cent vs 58 per cent; P=0.050), and higher non-relapse mortality (22 per cent vs 5 per cent; P=0.013).
Mono-cellular therapy (n=127) was associated with higher one-year incidence of grade 2-4 acute graft-versus-host disease (38 per cent vs 25 per cent; P=0.007) and cytomegalovirus (CMV) reactivation (51 per cent vs 37 per cent; P=0.021) compared with mono-immunotherapy (n=120). However, on multivariable analysis, treatment modality was not independently associated with reactivation of CMV or Epstein-Barr virus, or GVHD.
The new data suggest that cellular therapy confers a survival advantage over antibody-based immunotherapy when used as bridging to HSCT in patients with active R/R B-ALL. Comparable outcomes are observed in MRD+ patients.
