Blinatumomab in Ph-like Acute Lymphoblastic Leukemia – an Institutional Experience

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Background Blinatumomab is a landmark treatment for B-cell acute lymphoblastic leukemia (B-ALL) with approval in relapsed/refractory (R/R) and minimal residual disease (MRD) positive settings. Philadelphia chromosome-like (Ph-like) disease has been recognized as a high-risk subset (Jain et al, Blood 2017). However, efficacy of novel immunotherapies, such as blinatumomab, in these patients has not been described. Methods A retrospective chart review of all B-ALL patients diagnosed and/or treated since onset of standardized, Ph-like testing at our shared institutions was performed using clinical/pathological databases. Testing consisted of either 1) Ph-like FISH for CRLF2, ABL1, ABL2, JAK2, PDGFRb, or 2) ALL FISH panel with reflex gene fusion transcript analysis. Results 14 patients who received blinatumomab for R/R or MRD-positive disease were identified (8 R/R; 7 MRD-positive treatment settings – Table 1). 1 received blinatumomab for both indications at different time intervals. The majority of patients were Latino (79%) with CRLF2 rearrangement with age range (19-60, median 26). Most (71%) received induction therapy with pediatric-based regimen. Relapsed/Refractory Outcomes: Patients were treated for primary refractory to previously CR2 disease. 2 proceeded to allogeneic hematopoietic stem cell transplantation (allo-HSCT), with some (42%) refractory to treatment. No neurological (N) or cytokine release syndrome (CRS) toxicity of grade 3 or higher was noted. With allo-HSCT patients censored at time of transplant, mean event-free survival (EFS) was 3.1 months. MRD-positive Outcomes: Patients were treated for MRD-positive disease for CR1 (bridge to transplant) to after allo-HSCT. Remarkably, all 7 patients successfully achieved MRD-negative status. One patient, previously treated with blinatumomab in R/R setting with disease progression, had complete disease eradication post allo-HSCT in CR3. 2 N events of grade 3 or higher (aphasia, seizure) were noted, with both patients tolerating re-challenge. No CRS was seen. Conclusions Ph-like ALL is a challenging disease with clear high-risk implications; here we report our institutional experience with blinatumomab in Ph-like ALL. Blinatumomab was effective for select patients with R/R disease. However, it was more successful in MRD-positive ALL with all patients achieving MRD-negative status. Neurological toxicity was observed in 2 patients; both subsequently tolerated re-challenge. Ph-like ALL patients are more likely to remain MRD-positive after induction therapy (Jain et al, Blood 2017); utilizing blinatumomab as frontline or for MRD in first CR may improve outcomes. Further investigation with larger sample size and multi-center experience is required to fully determine the efficacy and role of blinatumomab, other immunotherapies, and allo-HSCT in the treatment of Ph-like ALL.