Subcutaneous blinatumomab (Blincyto) generated high response rates and encouraging survival outcomes across 2 dosing regimens in heavily pretreated patients with relapsed/refractory, Philadelphia chromosome (Ph)–positive B-cell acute lymphoblastic leukemia (B-ALL), according to findings from a phase 1/2 trial (NCT04521231) presented at the 2026 EHA Congress.1
In the total population (n = 16), the complete response (CR)/CR with partial hematologic recovery (CRh) rate within 2 subcutaneous blinatumomab cycles was 81.3%, and among these patients, the rate of minimal residual disease (MRD) response of less than 10–4 leukemic blasts detected was 76.9%. Additionally, the CR/CRh/CR with incomplete count recovery (CRi) rate was 93.8%, and among these patients, the rate of MRD negativity at a threshold of 10–4 was 80.0%.
Seven patients died from any cause. At a median follow-up of 16.3 months (95% CI, 12.2-20.8), the median overall survival (OS) was 19.4 months (95% CI, 3.9-not evaluable [NE]), and the estimated 12-month OS rate was 72.5% (95% CI, 42.1%-88.8%). Overall, patients completed a median of 2.0 blinatumomab cycles (range, 0.0-5.0).
Among patients who received subcutaneous blinatumomab at the 250-μg/500-μg dose (n = 8), the CR/CRh rate within 2 cycles was 75.0%, and the MRD-negativity rate among these patients was 83.3%. The CR/CRh/CRi rate was 87.5%, and the MRD-negativity rate among these responders was 85.7%. Five patients died from any cause. At a median follow-up of 22.0 months (95% CI, 1.9-NE), the median OS was 15.2 months (95% CI, 0.6-NE), and the estimated 12-month OS rate was 60.0% (95% CI, 19.5%-85.2%). Patients in this cohort completed a median of 2.0 blinatumomab cycles (range, 0.0-5.0).
Among patients who received subcutaneous blinatumomab at the 500-μg/1000-μg dose (n = 8), the CR/CRh rate within 2 cycles was 87.5%, and the MRD-negativity rate among these responders was 71.4%. The CR/CRh/CRi rate was 100.0%, and the MRD-negativity rate among these patients was 75.0%. Two patients died from any cause. At a median follow-up of 15.5 months (95% CI, 1.2-NE), the median OS was NE (95% CI, 3.9-NE), and the estimated 12-month OS rate was 85.7% (95% CI, 33.4%-97.9%). Patients in this cohort completed a median of 1.5 blinatumomab cycles (range, 1.0-5.0).
“These outcomes were achieved despite prior TKI exposure, limited subsequent hematopoietic stem cell transplant [HSCT] consolidation, and minimal CAR T-[cell therapy] use,” lead study author Elias Jabbour, MD, and coauthors wrote in the poster.
Jabbour is a professor in the Department of Leukemia in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.
What was the design of this phase 1/2 trial of subcutaneous blinatumomab in relapsed/refractory B-ALL?
“The subcutaneous delivery of blinatumomab is aimed to improve efficacy through enhanced dose exposure, simplify preparation and administration, and support patient convenience,” the authors wrote in the poster.
This phase 1/2 trial enrolled adult patients with B-ALL who were refractory to primary induction therapy or at least 1 salvage therapy, were untreated upon first or later relapse, had at least 5% bone marrow blasts, and had an ECOG performance status of 2 or lower. Prior treatment with CD19-directed therapy was permitted if blasts still expressed CD19.
Subcutaneous Blinatumomab in R/R Ph+ B-ALL: Phase 1/2 Data Highlights
- Subcutaneous blinatumomab was effective in a heavily pretreated population with high disease burden (n = 16), achieving a total population CR/CRh rate of 81.3% and a CR/CRh/CRi rate of 93.8% within 2 cycles.
- Survival outcomes for the total population were promising, with an estimated 12-month OS rate of 72.5% (95% CI, 42.1%88.8%).
- The median OS in the overall population was 19.4 months (95% CI, 3.9-NE) at a median follow-up of 16.3 months (95% CI, 12.2-20.8).
In the dose-escalation phase, patients started with subcutaneous blinatumomab at 250 μg once daily or 500 μg once daily during cycle 1 days 1 through 7, then at 500 μg thrice weekly or 1000 μg thrice weekly, respectively, during cycle 1 days 8 through 26 and cycles 2 through 5 for the remainder of cycle 1 and cycles 2 through 5. In the dose-expansion phase, patients were treated at the same doses and schedules. In the pharmacokinetic (PK) evaluation phase, patients followed the 500-μg/1000-µg dosing schedule. The patients treated at the 250-μg/500-μg dose in the escalation and expansion phases were pooled to comprise the 250-μg/500-μg cohort, and the patients treated at the 500-μg/1000-μg dose in the expansion and PK phases were pooled to comprise the 500-μg/1000-μg cohort.
The primary end point was CR/CRh rate. Secondary end points included CRi rate, MRD-negativity rate, HSCT status, OS from the first dose of subcutaneous blinatumomab, and safety/tolerability.
What data have been previously reported with subcutaneous blinatumomab in relapsed/refractory Ph-positive B-ALL?
Previously, the phase 1b portion of the trial showed that subcutaneous blinatumomab had antileukemic activity and a manageable safety profile in patients with relapsed/refractory B-ALL. At a data cutoff of September 15, 2023, at the end of 2 cycles, the CR/CRh rate was 85.7% among patients treated at the 250-μg/500-μg dose (n = 14) and 92.3% among those treated at the 500-μg/1000-μg dose (n = 13).2 The MRD negativity rates among responders were 75.0% and 100.0%, respectively.
What were the characteristics of patients with relapsed/refractory B-ALL treated with subcutaneous blinatumomab in this phase 1/2 trial?
The authors of the current phase 1/2 analysis noted that this trial population was heavily pretreated and had a high disease burden.1 In the total population, patients had a median age of 49.0 years (range, 19.0-72.0), and most were male (68.8%), White (81.3%), and not Hispanic/Latino (93.8%). The median bone marrow blast percentage was 60.0% (range, 5.0%-95.0%). Patients received a median of 3.5 prior lines of treatment (range, 1-7), including continuous intravenous blinatumomab (37.5%), CAR T-cell therapy (37.5%), HSCT (50.0%), and inotuzumab ozogamicin (Besponsa; 56.3%). In total, 6.3% of patients had primary refractory disease at enrollment, 56.3% of patients relapsed at any time after allogeneic HSCT, and no patients had extramedullary disease at diagnosis.
All patients had received a TKI before subcutaneous blinatumomab. During the study, 50.0% of patients received a concurrent TKI during treatment, 25.0% of patients received a concurrent TKI during cycle 1, and 56.3% of patients continued their concurrent TKI after completing subcutaneous blinatumomab treatment. The median duration of TKI treatment after subcutaneous blinatumomab was 9.5 months (range, 1.1-19.7).
Notably, of the 6 patients with ongoing long-term follow-up, 2 are receiving ongoing TKI therapy as of November 13, 2025.
What additional efficacy findings were seen with subcutaneous blinatumomab in relapsed/refractory B-ALL?
“[The] majority of the patients did not receive subsequent cellular therapy with HSCT and/or CAR T-cell therapy,” the authors explained. “Patients with prior and/or concurrent TKI therapy received subcutaneous blinatumomab, consistent with the clinical use of TKIs in Ph-positive B-ALL.”
In the total population, 31.3% of patients received HSCT following subcutaneous blinatumomab, 20.0% of whom received CAR T-cell therapy. Responses at latest assessment prior to HSCT included CR/CRh (60.0%; MRD-negativity rate, 66.7%) and CR/CRh/CRi (80.0%; MRD-negativity rate, 75.0%). Among the patients who did not receive HSCT (68.8%), 18.2% received CAR T-cell therapy.
In the 250-μg/500-μg population, 25.0% of patients received HSCT following subcutaneous blinatumomab, none of whom received CAR T-cell therapy. Responses at latest assessment prior to HSCT included CR/CRh (50.0%; MRD-negativity rate, 0.0%) and CR/CRh/CRi (100.0%; MRD-negativity rate, 50.0%). Among the patients who did not receive HSCT (75.0%), 33.3% received CAR T-cell therapy.
In the 500-μg/1000-μg population, 37.5% of patients received HSCT following subcutaneous blinatumomab, none of whom received CAR T-cell therapy. Responses at latest assessment prior to HSCT included CR/CRh (66.7%; MRD-negativity rate, 100.0%) and CR/CRh/CRi (66.7%; MRD-negativity rate, 100.0%). Among the patients who did not receive HSCT (62.5%), none received CAR T-cell therapy.
“No new safety signals were observed among patients with relapsed/refractory Ph-positive B-ALL. These findings support further evaluation of subcutaneous blinatumomab across Ph-positive B-ALL settings,” the authors concluded.
References
- Jabbour E, Lussana F, Rambaldi A, et al. Subcutaneous blinatumomab for patients with relapsed/refractory Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia: results from a phase 1/2 study. Presented at: 2026 EHA Congress, June 11-14, 2026; Stockholm, Sweden. Abstract PS1481.
- Jabbour E, Zugmaier G, Agrawal V, et al. Single agent subcutaneous blinatumomab for advanced acute lymphoblastic leukemia. Am J Hematol. 2024;99(4):586-595. doi:10.1002/ajh.27227
