Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL), also referred to as BCR-ABL1–like ALL, is a high-risk subset with a gene expression profile that shares significant overlap with that of Ph-positive (Ph+) ALL and is suggestive of activated kinase signaling. 

The data presented for Phase III trial E1910 trial demonstrated that of the total participants, 239 patients (86%) achieved a complete response (CR) or complete response with incomplete count recovery (CRi) following induction therapy (215 with CR and 24 with CRi). A total of 169 patients advanced to Step 3, including 132 who were measurable residual disease negative (MRD−) and 37 who were MRD positive (MRD+). Among the MRD− patients, 66 were randomized to receive either blinatumomab or continued chemotherapy. Treatment completion in the blinatumomab group varied: 9% completed one cycle, 27% completed two cycles, 3% completed three cycles, and 61% completed all four cycles. During Step 3, eight patients from the blinatumomab arm and 11 from the chemo arm discontinued treatment due to reasons unrelated to relapse or death. Similarly, during the maintenance phase, six blinatumomab and 10 chemo patients discontinued treatment for similar reasons. Overall, 45% of MRD− patients completed protocol-defined maintenance therapy.

In terms of efficacy, the addition of blinatumomab significantly improved outcomes. The 3-year overall survival (OS) rates for 30–54 years were 92% for the blinatumomab group versus 67% for chemotherapy (HR 0.20, 95% CI: 0.08–0.54; p = 0.002), and 3-year relapse-free survival (RFS) rates were 86% and 66%, respectively (HR 0.37, 95% CI: 0.17–0.81; p = 0.01). Hematopoietic cell transplantation (HCT) was received in the study by 11 patients in each arm and off the study by an additional five blinatumomab and eight chemo patients.

Subgroup analysis revealed particularly strong results in younger patients aged 30–39 years. Out of 102 in this age group, 87 achieved CR/CRi, and 47 MRD-negative patients were randomized (21 to blinatumomab and 26 to chemo). Notably, high molecular risk disease was more prevalent in the blinatumomab group (29%) compared to the chemo group (15%). In this subgroup, 3-year OS was 100% for blinatumomab and 73% for chemo (p = 0.009), while 3-year RFS was 90% versus 69% (p = 0.03). Among 19 patients with BCR::ABL1-like disease who were randomized, both 3-year OS and RFS were 100% for the blinatumomab arm, compared to just 45% in the chemotherapy group (p = 0.02 for both). Seven of these patients underwent HCT.

Safety data showed that Grade 4 sepsis occurred in 8% of blinatumomab-treated patients and 6% in the chemo arm. Two patients in the blinatumomab group experienced fatal intracranial hemorrhage. Importantly, a body mass index (BMI) of ≥30 kg/m² did not adversely affect either OS or RFS.

KOL insights

“These results and the pediatric COG AALL 1731 data suggest that blinatumomab should be incorporated into the care of all adolescents and young adults with B ALL. Further studies should evaluate the potential to increase MRD negativity and decrease the use of chemotherapy and HCT.” – Expert Opinion

Conclusion

BLINCYTO (blinatumomab), developed using Amgen’s BiTE (bispecific T-cell engager) technology, marked a pivotal shift in oncology as the first commercially successful bispecific antibody to receive FDA approval in 2014, following the earlier approval—but eventual market withdrawal—of catumaxomab. While catumaxomab was the first bispecific antibody approved (for malignant ascites), it was soon withdrawn from the market for commercial reasons, leaving BLINCYTO to establish the foundation for the bispecific antibody class in clinical oncology. As a BiTE targeting CD19 on B cells and CD3 on T cells, BLINCYTO offered a novel immunotherapeutic approach, particularly for patients with B-cell acute lymphoblastic leukemia in minimal residual disease (MRD)-positive and relapsed/refractory settings. Its clinical success not only redefined treatment options for B-cell malignancies but also validated the bispecific platform, catalyzing the development of next-generation agents such as Genentech’s COLUMVI (glofitamab) and Regeneron’s ODSPONO (odronextamab), currently advancing in B-cell non-Hodgkin lymphomas.

In the context of ALL, BLINCYTO remains the dominant bispecific therapy, competing primarily with CAR-T therapies like KYMRIAH and TECARTUS—especially in pediatric and heavily pretreated populations. Although both BLINCYTO and KYMRIAH are approved in pediatric ALL after multiple prior treatments, BLINCYTO is indicated specifically for Philadelphia chromosome-negative (Ph−) cases, whereas KYMRIAH is Ph-status agnostic. 

Despite increasing competition from cellular and antibody-based therapies, BLINCYTO continues to stand out due to its unique mechanism, clinical durability, and broad adoption. Its emergence not only redefined the bispecific class but also set a precedent for immune-engaging therapies, cementing its place as a cornerstone in the evolving landscape of leukemia treatment.