Efficacy of short-course versus standard-course blinatumomab in patients with relapsed/refractory or MRD-positive B-cell acute lymphoblastic leukemia

Abstract

Abstract Introduction Blinatumomab, a bispecific antibody targeting CD3/CD19, can significantly improve the complete remission (CR) rate, measurable residual disease (MRD) clearance, and survival in patients with relapsed and refractory (R/R) or newly diagnosed B-ALL, especially those with MRD-positive (MRD+) disease. Although clinical studies and guidelines recommend administering blinatumomab in a 28-day cycle, prospective studies have shown that a 14-day short course of blinatumomab combined with low-dose chemotherapy for first-line treatment is not significantly different from the standard cycle in terms of early efficacy. However, the clinical efficacy of short-course blinatumomab remains not fully understood. AIMS To compare the differences in CR rate, MRD negative rate, and survival outcomes between the 14-day and >14-day courses of blinatumomab in B-ALL patients. To assess the clinical benefit for patients receiving a shortened 14-day course of blinatumomab. METHODS: This multicenter retrospective study was conducted from March 2022 to July 2025 on patients with B-ALL who had detectable leukemia burden, defined as being at least MRD-positive, after one cycle of standard chemotherapy or those who were relapsed or refractory. These patients were treated with blinatumomab as reinduction therapy and were divided into two cohorts: those with a treatment duration of ≤14 days (12-14 days) and those with a treatment duration of >14 days. The outcomes assessed included CR rate, MRD-negative rate, overall survival (OS), and progression-free survival (PFS), with comparisons made between the two cohorts. Hematopoietic toxicity, cytokine response syndrome (CRS), and infections were also evaluated. RESULTS: A total of 119 B-ALL patients with detectable leukemia burden were analyzed, including those with high leukemia burden (>50% blast cells) (n = 36), intermediate burden (5-50%) (n = 35), and low burden (≤5% and MRD+) (n = 48). These patients received either ≤14 days (12-14) (n = 50) or >14 days of blinatumomab (n = 61), including 21 days (15-21 days) (n = 30) and 28 days (22-28 days) (n=31). Cohort analysis revealed no significant differences in CR/CRi rates (76.67% vs. 76.19%, P = 0.99) and MRD-negative rates (66.67% vs. 73.81%, P = 0.602) between the two cohorts of ≤14 days and >14 days of blinatumomab for reinduction therapy in patients with medium-to-high leukemia burden. Similarly, there was no significant difference in the MRD-negative rate (89.47% vs. 90%) between the two cohorts in patients with MRD-positive status prior to blinatumomab. The MRD-negative rate in patients with medium-to-high leukemia burden was significantly lower than in those with a low burden (70.83% vs. 89.74%, P = 0.03). For patients who had not achieved CR/CRi or MRD negativity after 14 days of blinatumomab (n = 37), extending treatment to 21 or 28 days did not significantly increase the CR/CRi rate or MRD negativity rate. Notably, in high-load patients (n = 17) who received >14 days of blinatumomab treatment, the CR/CRi rate and MRD-negative rate were 70.59% (12/17) and 88.24% (15/17), respectively, which were slightly higher than those at 14 days (both CR rate and MRD-negative rates were 64.71% (11/17)). However, the differences were not statistically significant (both P values were > 0.05). For MRD+ patients (n = 9), the MRD-negative rate at 14 days was 77.78% (7/9), which remained unchanged at 21 days. With a median follow-up of 21.47 months, the median progression-free survival (PFS) in the 14-day cohort was 9.90 months, compared to 9.33 months in the >14-day cohort. The 1-year PFS rates were 46.6% (95% CI 36.2-60.1) and 46.4% (95% CI 34.7-62.2), respectively, with no significant differences observed between the two cohorts. Regarding toxicity, there were no significant differences in the incidence and severity of CRS between the two cohorts. Lymphocyte depletion was more pronounced in the >14-day cohort, with an infection rate of 49.27% (34/69), which was significantly higher than the 28% (14/50) in the ≤14-day cohort (P = 0.0036). However, there was no significant difference in infections of grade ≥ 3. CONCLUSIONS: Recognizing the limits of a retrospective comparison, a 14-day course of blinatumomab yields response rates and survival outcomes similar to the standard course, particularly in patients with a low leukemia burden. Patients with high tumor burden may benefit from more than 14 days of treatment.