Short-duration blinatumomab for residual disease eradication as a bridge to transplant in B-ALL: Pediatric and adult outcomes in a resource-limited context Free

Background Blinatumomab is considered a standard of care for patients with B-cell acute lymphoblastic leukemia (B-ALL) and measurable residual disease (MRD); however, the ideal treatment dose for MRD is unknown. Preliminary data suggest that short courses of blinatumomab may be effective in lower disease burden states. At our institution, parallel trials have been implemented using short courses of blinatumomab in pediatric and adult patients with B-ALL in complete response (CR) and with detectable MRD who are candidates for hematopoietic cell transplantation (HCT).

Objective: To describe the efficacy and safety of a single short course of blinatumomab as a bridge to HCT.

Patients and Methods Adult and pediatric patients with CD19+ B-ALL, ≤5% blasts and an available donor for HCT were included. In adults, blinatumomab was administered at a fixed dose of 175 ug for 7 days in an in-patient setting (NCT06886074); for children, the dose was 5 ug/m²/day for 4-7 days, with a ramp-up to 15 ug/m²/day for up to 21 days as outpatients. Disease assessment was performed after 1 cycle and HCT was intended to be performed after at least 2 weeks after finishing blinatumomab in responders using matched or haploidentical sibling donors and peripheral blood stem cells. Conditioning for children was melphalan-based plus 2 Gy total body irradiation (TBI) in haploidentical grafts; for adults 12 Gy total marrow and lymphoid irradiation (TMLI) (NCT06209190). Graft-versus-host disease (GVHD) prophylaxis was post-transplant cyclophosphamide, tacrolimus and mycophenolate. The co-primary outcomes were MRD negativity by next-generation flow cytometry, defined as ≤.001% after blinatumomab and the achievement of transplantation. Secondary outcomes included the frequency of adverse events, overall survival (OS) and relapse-free survival (RFS).

Results Twenty patients were included, 19 Ph-negative ALL, with a median age of 10 years (0.8–59 years), n=8 were ≥18 years, and 65% were men. The average number of prior treatment lines was 3 (2–5), 35% were primary refractory, and 65% had relapsed at least once. Ninety percent (n=18) achieved negative and undetectable MRDx10^-5after a single reduced course of blinatumomab (100% in adults; 83.3% in children) and proceeded to successful HCT. N=2 did not achieve MRD negativity and could not achieve HCT. CRS occurred in 35% (all grade 1), ICANS in 15% (n=2 grade 1, n=1 grade 3). No pre-HCT mortality events occurred nor other grade≥3 adverse events. Sixteen patients received haploidentical grafts and 2 matched sibling grafts. All patients who received HCT remained MRD-negative after day 60. Following HCT n=10 (50%) had acute GVHD, n=1 grade 3, the rest were grades 1-2. (42%) 1 was severe (7%).

After a median follow-up of 33 months, one adult patient had an isolated relapse to the iris at 10 months which later progressed to the skin, and one pediatric patient had a bone marrow relapse 4 months after HCT. OS at 24 months was 63%, median NR (95% CI 22.97-43.15), EFS at 24 months was 55%, with a median of 42 months (95% CI 4.39-79.60%). N=2 died after HCT in remission due to pneumonia and a thromboembolic event.

Conclusions A short-course of blinatumomab is effective, demonstrating that it can be an adaptable alternative in low- and middle-income countries as a bridge to HCT for R/R patients in CR with detectable MRD.