Short-term blinatumomab regimen in newly diagnosed induction and MRD-negative consolidation treatment of B-cell acute lymphoblastic leukemia

Abstract

Abstract Background: Blinatumomab, a bispecific antibody engaging CD3 positive T cells to CD19 positive tumor cells, has demonstrated efficacy in relapsed/refractory and minimal residual disease (MRD)-positive acute lymphoblastic leukemia (ALL). In recent years, blinatumomab has been increasingly used in newly diagnosed and MRD-negative patients, especially used in a 28-day treatment cycle. Here, we investigated the efficacy of a shorter 14-day regimen and its impact on immune cell dynamics. Methods We conducted a retrospective real-world study of B-ALL patients receiving blinatumomab for induction or MRD-negative consolidation from Jan 2022 to May 2025. Data were collected from two centers. Results In the induction cohort (n=49, median age 41y), there're 11 Ph-positive (Ph+) and 38 Ph-negative (Ph-) cases. Among the Ph+ patients, 7 received a 14-day regimen and 4 received a 28-day regimen; while among the Ph- patients, 35 received a 14-day regimen and 3 received a 28-day regimen. All Ph+ patients underwent blinatumomab combined with TKI for induction therapy, achieving a composite complete remission rate (CRc) of 100%, with 90.1% reaching CMR after one cycle. Ph- patients received blinatumomab either as monotherapy or combined with chemotherapy/venetoclax for induction therapy, achieving a CRc of 86.5% and MRD negativity in 87.5% of cases. With a median follow-up of 7.5 months, the 2yOS and 2yEFS for Ph+ patients were 100% and 85.71% respectively. For Ph- patients, the 2yOS and 2yEFS were 100% and 31.68% in the 14-day regimen group, and 100% and 66.67% in the 28-day regimen group, respectively. No significant difference was observed between the 14-day and 28-day regimens in Ph+ patients; however, among Ph- patients, blinatumomab monotherapy and the 14-day regimen might be associated with inferior prognosis, which requires validation with a larger sample size. In the consolidation cohort (n=54, median age 46y), there're 28 Ph+ and 26 Ph- cases. The average number of blinatumomab consolidation cycles was 2.4 (range, 1–8) for Ph+ patients and 2.6 (range, 1–15) for Ph- patients. All Ph+ patients received blinatumomab in combination with TKI, among whom 22 received the 14-day regimen and 6 received the 28-day regimen. One out of 28 Ph+ patients experienced MRD reversion after consolidation and subsequently switched to other regimens. The 2yOS for Ph+ patients receiving the 14-day and 28-day regimens was 100% and 94.44% (p=0.56) respectively, while the 2yEFS was 100% and 88.54% (p=0.42). Notably, only one Ph+ patient in this cohort underwent allo-HSCT. Most Ph- patients (23/26) receied blinatumomab monotherapy as consolidation, and 23 received the 14-day regimen and 3 received the 28-day regimen. The 2yOS for Ph- patients receiving the 14-day and 28-day regimens was 100% and 88.54% (p=0.63) respectively, with the 2yEFS was 100% and 78.24% (p=0.40). One Ph- patient experienced MRD reversion, and 9 patients received allo-HSCT. The 2-year OS for Ph- patients with and without allo-HSCT was 100% and 83.92% (p=0.28), with the 2-year EFS was 85.71% and 79.33% (p=0.71). It appears that in the era of targeted therapy, B-ALL patients may achieve favorable outcomes without HSCT. We also analyzed T cell subset dynamics in 9 patients following blinatumomab. All patients exhibited increased PD-1 expression on both CD4+ and CD8+ T cells, and the frequencies of CD8+ naiev T cells, CD8+ effector T cells, and CD8+ memory T cells were expanded, which were consistent with previous reports using 28-day regimen. However, in one non-responder, the proportion of CD8+ effector T cells didn't increased compared with baseline, suggesting that early expansion of CD8+ effector T cells may serve as a predictor of treatment response. Unexpectedly, 8 out of 9 patients showed a shift in CD4+ T cell polarization from Th1 toward Th2/Th17 after treatment. The underlying mechanism remains unclear and needs further investigation. Nonetheless, this observation raises the question of whether restoring Th1 dominance could enhance the anti-leukemic efficacy of blinatumomab. Conclusion Our study suggests that a 14-day blinatumomab regimen may be appropriate for induction and MRD-negative consolidation in Ph+ ALL. For Ph- ALL, a 28-day regimen remains preferred for induction, while 14-day can be considered for MRD-negative consolidation. Moreover, our findings further support that early expansion of CD8+ effector T cells may serve as a predictor of treatment response.