ECOG-ACRIN E1910 subgroup analysis: Impact of age and MRD on blinatumomab outcomes in newly diagnosed Ph− B-ALL

Patients with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (B-ALL) who achieve complete remission and minimal residual disease (MRD) negativity with conventional chemotherapy often relapse.

Blinatumomab is a U.S. Food and Drug Administration (FDA) approved bispecific T-cell engager for the treatment of relapsed/refractory (R/R) ALL and MRD positive ALL in 1st or 2nd complete remission. The ALL Hub previously reported preliminary results from the ECOG-ACRIN E1910 study (NCT02003222) of blinatumomab consolidation in patients with newly diagnosed Philadelphia chromosome-negative B-ALL. Below, we summarize the impact of age and MRD level in this study, as presented by Mattison at the European Hematology Association (EHA) 2023 Congress.¹

Study design

ECOG-ACRIN E1910 is a randomized phase III trial conducted across the US, Israel, and Canada which included adult patients with Philadelphia chromosome-negative B-ALL. Patients were randomized 1:1 to receive either blinatumomab + chemotherapy or chemotherapy alone. The full study design is outlined here.

The primary endpoint was overall survival (OS) between the two arms in MRD-negative patients. The subgroup endpoints analyzed outcomes based on age <55 or ≥55 years as well as the depth of MRD <0.01%; MRD status was determined centrally by 6-color flow cytometry with a level of sensitivity of 0.01%.

Results

Of the 488 patients enrolled, 224 were randomized to receive either blinatumomab plus chemotherapy (n = 112) or chemotherapy alone (n = 112). The median age was 51 years.

• Following induction, the complete remission or complete remission with incomplete hematologic recovery rate was 81%, and 22 patients in each arm proceeded to allogeneic hematopoietic stem cell transplantation.
• No new safety signals were reported.
• The median OS was not reached versus 71.4 months in the blinatumomab + chemotherapy arm versus chemotherapy arm, respectively (p = 0.003).
• For patients aged <55 years, the median OS was not reached in both arms (p < 0.001).
• For patients aged ≥55 years, the median OS was not reached versus 71.4 months in the blinatumomab + chemotherapy and the chemotherapy arm, respectively (p = 0.47)
• For patients with undetectable MRD, the median OS was not reached in both arms (p = 0.038).
• For patients between undetectable MRD and <0.01%, the median OS was not reached versus 38 months in the blinatumomab + chemotherapy versus chemotherapy arm, respectively (p = 0.16).

Conclusion

In this randomized study, blinatumomab plus chemotherapy improved overall survival in MRD-negative patients with Philadelphia chromosome-negative B-ALL. There was significant benefit for those aged <55 years and patients with undetectable MRD, and no new safety signals were reported.