Introduction: Blinatumomab, a BiTE® (bispecific T-cell engager) molecule, is an effective treatment for relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) when administered as a 28-day continuous intravenous infusion (cIV). Results from the dose escalation, dose expansion, and pharmacokinetic evaluation parts of this phase 1/2 study of subcutaneous (SC) blinatumomab demonstrated an acceptable safety profile and high efficacy of two selected doses (NCT04521231; Jabbour et al, Lancet Haematol 2025). In this study, we present updated efficacy outcomes with an additional 7 months of follow-up for all patients who were enrolled and received at least one dose of SC blinatumomab.

Methods: In this multicenter phase 1/2 study, adult patients with R/R B-ALL received single-agent SC blinatumomab injection (0.3–1.2 mL) at two doses, either 250 µg once-daily (QD) for week 1 of cycle 1 followed by 500 µg thrice-weekly (TIW) (250/500 cohort) or 500 µg QD during week 1 followed by 1000 µg TIW (500/1000 cohort). Each cycle included 4 weeks of treatment and a 1-week treatment-free interval. Patients were to receive 2–5 cycles. Subsequent treatments, including hematopoietic stem cell transplant (HSCT) were collected in long-term follow-up (LTFU), which lasted two years following the first dose of SC blinatumomab. The primary endpoint in dose expansion was complete remission (CR) or CR with partial hematologic recovery (CRh) within two cycles. Key secondary endpoints were measurable residual disease (MRD) response rate, overall survival (OS) from the first dose of SC blinatumomab, HSCT status, relapse rate, and duration of response (DoR).

Results: As of July 3, 2025, 79 patients (median age: 52 years; females: 38%) were treated with SC blinatumomab and enrolled in cohorts which included LTFU; 31 in the 250/500 cohort and 48 in the 500/1000 cohort. At baseline, patients had received a median of 2 prior lines of therapy (range, 1–7), which included cIV blinatumomab in 17 (22%), chimeric antigen receptor T-cells in 14 (18%), HSCT in 23 (29%), and inotuzumab ozogamicin in 26 (33%) patients. Fifteen patients (19%) had Philadelphia chromosome-positive (Ph+) B-ALL. Twelve patients (15%) were refractory to frontline therapy. Median bone marrow blast percentage was 65% (range, 5%–98%). Patients received a median of 2 cycles (range, 1–5).

CR/CRh was achieved within two cycles in 61/79 patients (77%); 23/31 (74%) in 250/500 cohort and 38/48 (79%) in 500/1000 cohort. A total of 20 (87%) and 34 (89%) of CR/CRh responders in 250/500 and 500/1000 cohorts, respectively, were negative for MRD (<10-4; qPCR or flow cytometry). At a median follow-up of 13.7 months, the estimated 12-month OS rate (N=79) was 69.1% (95% CI: 57.1%, 78.3%) overall. In the 250/500 and 500/1000 cohorts, the median follow-up was 11.4 and 16.3 months with estimated 12-month OS rates of 72.3% (95% CI: 52.1%, 85.1%) and 67.4% (95% CI: 51.7%, 79.0%), respectively. No new safety signals were reported.

Among CR/CRh responders, the estimated 12-month OS rate was 80.2% (95% CI: 61.0%, 90.6%) in the patients who received HSCT (n=32; median age, 43 yrs; ≥55 yrs, 13%; Ph+, 16%) after treatment and 85.2% (95% CI: 65.2%, 94.2%) in those who did not receive HSCT (n=29; median age, 63 yrs; ≥55 yrs, 69%; Ph+, 24%). At data cutoff, 25 (78%) of CR/CRh responders who received HSCT were alive. Causes of death post-HSCT were leukemia (n=4), sepsis (n=1), cardiac arrest (n=1), and unknown (n=1). Among responders who did not receive HSCT, 22 (76%) were alive, 5 died (4 due to leukemia and 1 due to COVID-19), 1 was lost to follow-up, and 1 withdrew consent.

The median (range) DoR among CR/CRh responders was 18.4 (1.2–18.4) months overall, 18.4 months (3.2–18.4) in the 250/500 cohort and not estimable (NE) (1.2–11.0 months) in the 500/1000 cohort. Of the CR/CRh responders in the 250/500 and 500/1000 cohorts, respectively, 17 (74%) and 29 (76%) were alive without relapse at the last disease assessment date.

Conclusion: Consistent with prior findings, single-agent SC blinatumomab maintained durable remissions and OS in this extended follow-up analysis. These outcomes were observed across the 250/500 and 500/1000 doses and were independent of HSCT status. Compared to our previous report, this analysis includes additional follow-up and updated post-HSCT outcomes. These data support the continued development of SC blinatumomab as an effective treatment option for patients with R/R B-ALL.

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2025
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