Blinatumomab (BLINCYTO), developed by Amgen, is the first approved CD19-directed bispecific T-cell engager (BiTE®) immunotherapy and has become a cornerstone treatment for relapsed/refractory B-cell ALL. The drug has demonstrated substantial efficacy across multiple ALL settings, including measurable residual disease (MRD)-positive disease and relapsed Ph+ ALL, typically administered as a 28-day continuous intravenous infusion.

To address the practical limitations associated with prolonged infusion, Amgen has been developing an SC formulation designed to provide comparable exposure while significantly improving convenience for patients and treatment centers. Earlier studies in B-ALL demonstrated favorable pharmacokinetics and encouraging efficacy, supporting further evaluation in high-risk subgroups such as Ph+ ALL.

This ad hoc analysis evaluated 16 heavily pretreated adults with R/R Ph+ B-ALL enrolled in the Phase I/II SC blinatumomab study. Patients had received a median of 3.5 prior lines of therapy, with substantial prior exposure to HSCT, CAR-T therapy, intravenous blinatumomab, and multiple TKIs.

• A total of five patients (31%) underwent subsequent HSCT (250/500: 2/8 [29%]; 500/1000: 3/8 [38%]), of whom one in 500/1000 also received CAR-T therapy. 

• Two patients in 250/500 received CAR-T therapy without HSCT following SC blinatumomab.

Safety Outcomes-

Nine patients were alive at last contact; deaths were due to disease progression (n = 4), sepsis, multi-organ failure, and embolic infarcts (n = 1, each).

KOL Insights-

“Subcutaneous delivery has the potential to remove one of the major logistical barriers associated with blinatumomab therapy while preserving the potent anti-leukemic activity that has defined the BiTE platform.”– Expert Opinion

“The high MRD-negative remission rates seen in this heavily pretreated Ph+ population are encouraging, and support continued development of the subcutaneous formulation.”– Expert Opinion

Conclusion-

Ph+ ALL accounts for approximately 20–30% of adult ALL cases and remains a biologically aggressive subtype despite major advances with tyrosine kinase inhibitors. Relapsed disease continues to represent a significant therapeutic challenge, particularly in patients previously exposed to multiple targeted and cellular therapies. Achieving deep MRD-negative remissions remains a critical objective because molecular response strongly correlates with long-term outcomes.

In this Phase I/II analysis, SC blinatumomab produced high remission and MRD-negativity rates in a heavily pretreated Ph+ ALL population, including patients with prior HSCT, CAR-T therapy, and intravenous blinatumomab exposure. Importantly, efficacy was maintained alongside concurrent TKI administration without new safety concerns. These findings support further development of SC blinatumomab as a more convenient and potentially practice-enhancing treatment option across multiple Ph+ ALL settings.