Early Blinatumomab Findings Show Promising Outcomes in Pretreated B-Cell ALL

Therapy with subcutaneous blinatumomab demonstrated “high efficacy” and high rates of negative measurable residual disease (MRD) status with acceptable safety in heavily pretreated adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-cell ALL), suggested data from a phase Ib trial.

“These encouraging results could be practice-changing and warrant further exploration for patients with B-cell ALL,” wrote the authors, led by Elias Jabbour, MD, of the University of Texas MD Anderson Cancer Center in Houston, in the report published in the American Journal of Hematology.

The phase Ib trial evaluated blinatumomab doses of either 250 μg once a day in week one followed by 500 μg three times weekly (n=14) or 500 μg once daily in week one followed by 1,000 μg three times weekly (n=13). The primary endpoint was complete remission or complete remission with partial hematologic recovery within two cycles. MRD negativity was defined as less than 10⁻⁴ leukemic blasts.

By the data cutoff of September 15, 2023, 12 out of 14 (85.7%) patients in the lower-dose group achieved the primary endpoint, including nine (75.0%) who had negative MRD status. In the higher-dose group, 12 out of 13 (92.3%) patients achieved the primary endpoint and all 12 had negative MRD status.

The cohort had no cases of treatment-related grade 4 cytokine release syndrome (CRS) or neurologic events, and all cases of treatment-related grade 3 CRS and neurologic events were resolved via standard care or treatment interruption or discontinuation. The blinatumomab injections were reportedly well tolerated.

The authors acknowledged the study was limited by a small sample size, though they stated pharmacokinetic evidence of a dose-dependent increase in exposure, early large reductions of tumor load, and the combination of complete remissions with high rates of MRD negativity all corroborated the clinical conclusions.

In closing, Dr. Jabbour and colleagues suggested that “randomized, controlled trials are warranted to test these hypotheses.”

Reference

Jabbour E, Zugmaier G, Agrawal V, et al. Single agent subcutaneous blinatumomab for advanced acute lymphoblastic leukemia. Am J Hematol. 2024. doi:10.1002/ajh.27227