Real-world outcomes with blinatumomab as a bridging therapy for allogeneic hematopoietic stem cell transplantation in relapsed/refractory or measurable residual disease-positive B-cell acute lymphoblastic leukemia: A CIBMTR database analysis

Abstract Background: Blinatumomab has been used as an effective therapy for the treatment of adult and pediatric patients in various settings of B-cell acute lymphoblastic leukemia (B-ALL), including relapsed/refractory (R/R) and measurable residual disease-positive (MRD+) B-ALL, to induce complete remission (CR) and/or MRD-negative remission. The aim of this study was to evaluate the real-world transplant-related outcomes separately for patients with R/R and MRD+ B-ALL who received blinatumomab as bridging therapy for allogeneic hematopoietic stem cell transplantation (alloHSCT). Methods: This was an observational retrospective cohort study utilizing the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Pediatric (age < 18 years) and adult patients (age 18-75 years) with R/R or MRD+ B-ALL (MRD status was determined per participating centers' usual practice) who received blinatumomab as bridging therapy and remained in CR prior to proceeding to alloHSCT between 31 July 2017 and 31 May 2022 were included. Overall survival (OS) and leukemia-free survival (LFS) probabilities were estimated using the Kaplan-Meier method. Cumulative incidences of acute and chronic graft versus host disease (GVHD), infections, veno-occlusive disease or sinusoidal obstructive syndrome (VOD/SOS), disease relapse, and transplant-related mortality (TRM) were calculated. Results: The median follow-up from alloHSCT in the R/R and MRD+ B-ALL populations was approximately 3 years. Among patients with R/R B-ALL (n=215), the median age of was 22.2 (range: 0.5 to 72.0) years; 32.1% were in first complete remission (CR1) at the time of alloHSCT after multiple cycles of chemotherapy then blinatumomab beyond induction to attain CR, while 67.9% were in second or later complete remission (CR2+) at the time of alloHSCT; and 16.7% were MRD+ at the time of alloHSCT. As conditioning regimen for alloHSCT, 59.5% received myeloablative with total body irradiation (MAC-TBI); 16.3% received myeloablative without total body irradiation (MAC -Chemo); and 23.7% received nonmyeloablative or reduced intensity conditioning (RIC). For outcomes following alloHSCT, grade III/IV acute GVHD at 100 days after alloHSCT was 12.5% (95% CI: 8.3-17.5%); and chronic GVHD at 2 years after alloHSCT was 34.4% (95% CI: 28.0-41.1%). At 100 days after alloHSCT, VOD/SOS was 9.7% (95% CI: 5.8-14.3%); and infection was 13% (95% CI: 8-17.0%). At 3 years after alloHSCT, disease relapse was 22% (95% CI: 16-27%); TRM was 18% (95% CI: 13-24%); LFS was 60% (95% CI: 54-67%); and OS was 69% (95% confidence interval [CI]: 63-76%). Among patients with MRD+ B-ALL (n=201), the median age was 30.8 (range: 1.3 to 74.7) years; 74.1% were in CR1, while 25.9% were in CR2+ at the time of alloHSCT; and 22.9% were MRD+ at the time of alloHSCT. As conditioning regimen for alloHSCT, 56.7% received MAC-TBI; 15.4% received MAC-Chemo; and 27.9% received nonmyeloablative or RIC. For outcomes following alloHSCT, grade III/IV acute GVHD at 100 days after alloHSCT was 12.6% (95% CI: 8.2-17.6%), and chronic GVHD at 2 years after alloHSCT was 33.2% (95% CI: 26.7-39.9%). At 100 days after alloHSCT, VOD/SOS was 5.4% (95% CI: 2.5-9.3%); and infection was 16% (95% CI: 12-22%). At 3 years after alloHSCT, disease relapse was 26.0% (95% CI: 20-32%); TRM was 14.0% (95% CI: 10-19%); LFS was 60% (95% CI: 53-67%); and OS was 72% (95% CI: 66-78%). Conclusion: The study findings suggested that transplant-related outcomes with blinatumomab as a bridging therapy remain consistent with the broader literature, with high overall survival and low TRM. These results further suggest that blinatumomab remains an effective and safe bridging therapy in the real world.