Pediatric-inspired therapy and blinatumomab consolidation improve outcomes in young adults with Philadelphia-like acute lymphoblastic leukemia

Abstract

Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) is a high-risk subtype of B-cell ALL associated with poor response to induction chemotherapy, suboptimal measurable residual disease (MRD) clearance, and inferior survival outcomes compared to non-Phlike subtypes. We retrospectively analyzed 140 consecutive adult patients with Ph-like ALL treated at our institution. The median age was 33.5 years, and the majority harbored CRLF2 rearrangements (85%). IKZF1plus deletion and JAK mutations were identified in 26% and 37% of patients, respectively. The majority (75%) received pediatric-inspired regimens (PIR), which were associated with higher complete remission (CR) rates (p=0.034), reduced risk of relapse (p<0.001), and improved overall survival (p=0.008), but did not significantly improve MRD negativity (p=0.6) compared to non-PIR approaches. Notably, non-CRLF2–rearranged cases demonstrated lower CR rates (p=0.022). The presence of IKZF1plus predicted inferior relapse-free survival (RFS; p=0.032). Among patients who achieved MRD negativity following induction ± consolidation, blinatumomab consolidation was associated with lower risk of relapse (p=0.043) and showed a trend toward improved RFS (p=0.055). In a landmark analysis of young adult patients (<55 years) in MRD-negative first CR (CR1), allogeneic hematopoietic cell transplantation did not confer benefit in RFS (p=0.24) or relapse (p=0.124). Notably, young adult patients treated with PIR who achieved MRD-negative CR by clonoSEQ and subsequently received blinatumomab consolidation demonstrated excellent early outcomes despite low transplant rate. In conclusion, contemporary treatment strategies for Ph-like ALL in adults, including the use of PIR in younger adults, incorporation of blinatumomab in MRDnegative CR1, and risk-adapted transplant decisions, are associated with improved clinical outcomes.