Blinatumomab maintenance after allogeneic hematopoietic cell transplantation for B-lineage acute lymphoblastic leukemia

Abstract

Patients with B-lineage acute lymphoblastic leukemia (ALL) are at high-risk for relapse after allogeneic hematopoietic cell transplantation (HCT). We conducted a single center phase II study evaluating the feasibility of 4 cycles of blinatumomab administered every 3 months during the first year after HCT in an effort to mitigate relapse in high-risk ALL patients. Twenty-one of 23 enrolled patients received at least one cycle of blinatumomab and were included in the analysis. The median time from HCT to the first cycle of blinatumomab was 78 days (range, 44-105). Twelve patients (57%) completed all 4 treatment cycles. Neutropenia was the only grade 4 adverse event (19%). Rates of cytokine release (5% G1) and neurotoxicity (5% G2) were minimal. The cumulative incidence of acute GVHD grades 2-4 and 3-4 were 33% and 5%, respectively; two cases of mild (10%) and one case of moderate (5%) chronic GVHD were noted. With a median follow-up of 14.3 months, the 1-year overall survival, progression-free survival, and non-relapse mortality rates were 85%, 71%, and 0%, respectively. In a matched-analysis with a contemporary cohort of 57 patients, we found no significant difference between groups regarding blinatumomab's efficacy. Correlative studies of baseline and post-treatment samples identified patients with specific T-cell profiles as "responders" or "non-responders" to therapy. Responders had higher proportions of effector memory CD8 T-cell subsets. Non-responders were T-cell deficient and expressed more inhibitory checkpoint molecules, including TIM3. We found that blinatumomab post-allogeneic HCT is feasible, and its benefit is dependent on the immune milieu at time of treatment.

Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in Adults

“…To note, a recent phase 2 study demonstrated the feasibility and safety of post allo-HSCT blinatumomab based maintenance in 21 patients including 2 Ph+ ALL patients [ 116 ]. Several prospective trials are ongoing to clarify the implementation of post-allo HSCT maintenance ( Table 2 ).…”

Immunotherapy for Pediatric Acute Lymphoblastic Leukemia: Recent Advances and Future Perspectives

“…Therefore, blinatumomab gained accelerated approval by FDA to treat BCP ALL with MRD greater than or equal to 0.1% after the first or second CR. Moreover, a phase II study (NCT02807883) has proved the feasibility of blinatumomab maintenance following alloHSCT for patients with B-cell ALL at high-risk for relapse, with the 1-year overall survival (OS), progression-free survival (PFS), and nonrelapse mortality (NRM) rates of 85%, 71%, and 0%, respectively ( 30 ). In addition, to incorporate blinatumomab as part of upfront treatment for pediatric B-cell ALL, several trials are currently ongoing (NCT03643276 and NCT03914625) ( 31 ).…”

“…In the future, screening tumor markers to predict CD19-negative relapse should be paid more attention. What’s more, overexpression of checkpoint molecules including T-cell immunoglobulin and mucin domain 3 (TIM-3) on T cells and PD-L1 on tumor cells represented an additional potential escape mechanism from immunosurveillance ( 30 , 59 , 60 ). Adding immune checkpoint inhibitors to blinatumomab treatment thus overcoming resistance may be feasible ( 60 ) and are under clinical investigation (NCT03160079, NCT03512405 and NCT04546399).…”

Innovative Approaches to the Management of Acute Lymphoblastic Leukemia Across the Age Spectrum

“…93 The use of posttransplant maintenance strategies has been explored in ALL; post-HSCT TKI maintenance in adults with Ph1 ALL has been shown to reduce relapse and is generally recommended, 94,95 whereas post-HSCT maintenance approaches in PhÀ ALL are currently limited to early investigations. 96 The importance of MRD clearance before HSCT has been established and is now achievable in B-ALL after blinatumomab, 73 and post-HSCT MRD monitoring of the bone marrow or peripheral blood using sensitive next-generation sequencing-based technologies has been incorporated into clinical practice. 97 Finally, novel HSCT graft engineering approaches are offering the promise of reduced graft-versus-host disease with preserved or improved efficacy 98,99 and are now being tested in confirmatory clinical trials (NCT04013685).…”