In the frontline treatment, all those using blinatumomab for remission induction and first line unknown status achieved CR with a CR/CRi rate of 100% (14/14) after blinatumomab. In patients with available MRD records (n = 47), 87.2% (n = 41) achieved MRD negativity within 2 cycles of blinatumomab (Table 2). In the following cycles, 3 more patients achieved MRD remission with the overall MRD remission rate of 93.6% (44/47). Stratified by CR status at baseline, in 33 CR patients with available MRD records, 81.8% (27/33) achieved MRD remission within 2 cycles of blinatumomab and 90.9% (30/33) after the following cycles. Among 6 remission induction patients and 9 patients with unknown CR status, all (100%) achieved CR with MRD remission within the 2 cycles of blinatumomab.

In 28 R/R re-induction patients, CR/CRi rate was 50% (14/28) after blinatumomab treatment, with 64.2% (9/14) MRD negativity rate in CR patients. In 14 R/R patients with CR status before blinatumomab initiation, 90.9% (10/11) achieved MRD negative CR after blinatumomab. Overall, the MRD remission rate in R/R patients who achieved CR was 73% (19/26) within 2 cycles of blinatumomab treatment. One more patient achieved MRD remission in the following cycle (76.9%; 20/26; Table 2).

The median EFS was not reached (NR) in both frontline and R/R patients, and the 1-year EFS rate was 90.8% (95% CI: 67.0%, 97.0%) and 55.1% (95% CI: 30.0%- 74.0%), respectively (Fig. 2). The stratification of EFS by CR status at blinatumomab initiation showed a 1-year EFS rate of 93.3% (95% CI: 61.3%, 99.0%) and 100% (95% CI: not estimable [NE], NE) in the first-line consolidation and remission induction patients, respectively, whereas, R/R consolidation and re-induction patients showed a 1-year EFS rate of 66.8% (95% CI: 27.0%, 88.3%) and NE (95% CI: NE, NE), respectively (Table 2).

Kaplan-Meier curve for EFS in ND patients. a Overall and b Stratified by CR status before blinatumomab initiation and in R/R patients c Overall and d Stratified by CR status before blinatumomab initiation. Abbreviations: B-ALL, B-cell acute lymphoblastic leukemia; Blin, blinatumomab; CR, complete remission; EFS, event free survival; ND, newly diagnosed; R/R, relapsed/refractory

When stratified by Ph-chromosome status, the median EFS, without censoring for transplant and CAR-T, was NR in both Ph+ (95% CI: NE, NE) and Ph- (95% CI: 9.4, NE) B-ALL patients (Supplementary Fig. 1), and the 1-year EFS rate was 92.9% (95% CI: 59.1%, 99.0%) and 65.7% (95% CI: 41.8%, 81.7%) in Ph+ and Ph- B-ALL patients, respectively. The median EFS, with censoring for transplant and CAR-T, was also NR in both Ph+ (95% CI: 3.9, NE) and Ph- (95% CI: 7.7, NE) B-ALL patients, and the 1-year EFS rate was NR in Ph+ B-ALL patients and 48.0% (95% CI: 18.5%, 72.6%) in Ph- B-ALL patients.

On stratification by blinatumomab treatment line setting and Ph-chromosome status of B-ALL patients, the 1-year EFS (without censoring for transplant and CAR-T) was 100.0% (95% CI: 100.0%, 100.0%) in Ph+ ND patients and NR (95% CI: NE, NE) in Ph+ R/R patients receiving blinatumomab. The corresponding 1-year EFS rate was 83.0% (95% CI: 45.7%, 95.6%) in Ph- ND patients and 49.9% (95% CI: 20.2%, 73.9%) in Ph- R/R patients (Table 2).

The median RFS (without censoring for transplant and CAR-T) was NR in frontline blinatumomab remission induction patients and second-line re-induction R/R patients and 2.7 (95% CI: 1.0, NE) months in third-line R/R re-induction patients. Median EFS was NR in both frontline and R/R patients using blinatumomab for consolidation. The 1-year RFS rate was 100.0% (95% CI: 100.0% 100.0%) and 93.8% (95% CI: 63.2%, 99.1%) in frontline induction and consolidation patients, respectively, it was NR in both second-line and third-line R/R re-induction and consolidation patients (Table 2).

OS results in ND patients were NE. In R/R patients, median OS was NR and the 1-year OS rate was 70.9% (95% CI: 50.0%, 84.0%). Stratification of OS results by CR status in R/R patients showed a 1-year OS rate of 87.5% in consolidation patients and 69.9% in re-induction patients. The median DOR was NR in both frontline and R/R patients (Table 2).

During blinatumomab treatment, AEs of any grade were reported in 19.8% patients (19/96) (Table 3). The most common AE of any grade was CRS (7/96; 7.3%) followed by infection (6/96; 6.2%). Grade ≥ 3 AEs were observed in 12.5% (12/96) of patients with infection (4/96; 4.2%) being the most common grade ≥ 3 AE followed by CRS (3/96; 3.1%). No deaths due to blinatumomab related AEs were reported. Two patients discontinued the blinatumomab treatment due to AEs, one patient had Grade 3 neurotoxicity, and the other one had grade 3 infusion reaction; both recovered after treatment discontinuation.

During the follow-up period, in the ND group, 1 death was reported after 4 months post allo-transplantation due to transplantation related toxicity. In the R/R group, 13 patients discontinued blinatumomab treatment prematurely – 1 due to AE and 12 patients due to progressive diseases (PD), while 10 deaths were reported – 7 due to PD, and 1 each due to CRS induced by CAR-T, chemotherapy related toxicity, and chemotherapy related infection.