Contributions
Abstract: P359
Type: Poster presentation
Session title: Acute lymphoblastic leukemia - Clinical
Background
Children with high-risk first-relapse B-ALL have a poor prognosis. We previously reported that, as compared with chemotherapy, treatment with blinatumomab resulted in prolonged event‑free survival (EFS) and overall survival (OS) and higher rates of minimal residual disease (MRD) remission in a phase 3 trial (JAMA 2021;325:843-54; ASH 2021:Abs 1231).
Aims
Here we provide follow-up (FU) data as of Sep 2021, with a focus on survival and MRD response.
Methods
In this phase 3 trial (Amgen NCT02393859), children >28 days and <18 years old with high-risk first‑relapse B-ALL were randomized 1:1 after induction and 2 cycles of consolidation to receive either a third intensive multidrug chemotherapy consolidation or blinatumomab (15 μg/m2/day, 4 weeks, continuous IV infusion). Study enrollment required M1 (<5% blasts) or M2 (≥5% and <25% blasts) bone marrow (BM) at randomization. Patients with complete remission (CR, ie, M1 BM) after treatment could undergo allogeneic hematopoietic stem cell transplant (alloHSCT). EFS, the primary endpoint, was calculated from randomization to whichever occurred first of relapse or M2 BM after CR, failure to achieve a CR at the end of treatment, second malignancy, or death (any cause). Survival outcomes and response rates were analyzed by baseline MRD, ie, MRD at enrollment prior to chemotherapy or blinatumomab. Parents or a legally acceptable representative provided written informed consent.
Results
Enrollment was stopped based on the interim analysis for benefit of blinatumomab (7/17/19 primary analysis). The following results reflect an updated analysis as of Sep 2021. Between Nov 2015 and Aug 2019, 111 patients were randomized: 54 (49%) to blinatumomab and 57 (51%) to chemotherapy at 47 centers in 13 countries. Baseline characteristics were comparable in both arms as previously reported. After a median FU of 44 months, EFS was significantly higher with blinatumomab vs chemotherapy (at 4 years: 59% vs 27%, stratified log-rank p<0.001, hazard ratio [HR]: 0.35, 95% CI: 0.20-0.61). Blinatumomab also showed a strong benefit for the secondary endpoint of OS (at 4 years: 77% vs 49%, stratified log-rank p=0.002, HR: 0.34, 95% CI: 0.17-0.69). EFS, OS, and MRD remission (<10-4 blasts) were all improved with blinatumomab, both overall and by baseline MRD subgroup (< or ≥10-3) (Table 1a-b, Figure). Further, patients with and without extramedullary disease both had a benefit with blinatumomab. AlloHSCT in second CR was performed in 51/54 patients in the blinatumomab arm and in 39/57 patients in the chemotherapy arm. No new safety signals were identified. Second relapses occurred in 16/54 (30%) patients in the blinatumomab arm and 34/57 (60%) patients in the chemotherapy arm. In the blinatumomab arm, these second relapses were extramedullary in 5/54 patients, CNS in 5 (9.3%), 2 of which were solely CNS. In the chemotherapy arm, these second relapses were extramedullary in 8/57 patients, CNS in 3 (5.3%), 2 of which were solely CNS. CD19-negative relapse was seen in 3 patients in the blinatumomab arm (3/54) and 1 patient in the chemotherapy arm (1/57) prior to any subsequent CD19-directed therapy (ie, after study therapy).
Conclusion
In children with high-risk first-relapse B-ALL, treatment with 1 cycle of blinatumomab vs chemotherapy before alloHSCT resulted in superior EFS and improved OS and MRD response rates, all independent of baseline MRD. The incidence of CD19-negative relapse after blinatumomab was low.
Keyword(s): CD19, Minimal residual disease (MRD), Stem cell transplant, Survival
Abstract: P359
Type: Poster presentation
Session title: Acute lymphoblastic leukemia - Clinical
Background
Children with high-risk first-relapse B-ALL have a poor prognosis. We previously reported that, as compared with chemotherapy, treatment with blinatumomab resulted in prolonged event‑free survival (EFS) and overall survival (OS) and higher rates of minimal residual disease (MRD) remission in a phase 3 trial (JAMA 2021;325:843-54; ASH 2021:Abs 1231).
Aims
Here we provide follow-up (FU) data as of Sep 2021, with a focus on survival and MRD response.
Methods
In this phase 3 trial (Amgen NCT02393859), children >28 days and <18 years old with high-risk first‑relapse B-ALL were randomized 1:1 after induction and 2 cycles of consolidation to receive either a third intensive multidrug chemotherapy consolidation or blinatumomab (15 μg/m2/day, 4 weeks, continuous IV infusion). Study enrollment required M1 (<5% blasts) or M2 (≥5% and <25% blasts) bone marrow (BM) at randomization. Patients with complete remission (CR, ie, M1 BM) after treatment could undergo allogeneic hematopoietic stem cell transplant (alloHSCT). EFS, the primary endpoint, was calculated from randomization to whichever occurred first of relapse or M2 BM after CR, failure to achieve a CR at the end of treatment, second malignancy, or death (any cause). Survival outcomes and response rates were analyzed by baseline MRD, ie, MRD at enrollment prior to chemotherapy or blinatumomab. Parents or a legally acceptable representative provided written informed consent.
Results
Enrollment was stopped based on the interim analysis for benefit of blinatumomab (7/17/19 primary analysis). The following results reflect an updated analysis as of Sep 2021. Between Nov 2015 and Aug 2019, 111 patients were randomized: 54 (49%) to blinatumomab and 57 (51%) to chemotherapy at 47 centers in 13 countries. Baseline characteristics were comparable in both arms as previously reported. After a median FU of 44 months, EFS was significantly higher with blinatumomab vs chemotherapy (at 4 years: 59% vs 27%, stratified log-rank p<0.001, hazard ratio [HR]: 0.35, 95% CI: 0.20-0.61). Blinatumomab also showed a strong benefit for the secondary endpoint of OS (at 4 years: 77% vs 49%, stratified log-rank p=0.002, HR: 0.34, 95% CI: 0.17-0.69). EFS, OS, and MRD remission (<10-4 blasts) were all improved with blinatumomab, both overall and by baseline MRD subgroup (< or ≥10-3) (Table 1a-b, Figure). Further, patients with and without extramedullary disease both had a benefit with blinatumomab. AlloHSCT in second CR was performed in 51/54 patients in the blinatumomab arm and in 39/57 patients in the chemotherapy arm. No new safety signals were identified. Second relapses occurred in 16/54 (30%) patients in the blinatumomab arm and 34/57 (60%) patients in the chemotherapy arm. In the blinatumomab arm, these second relapses were extramedullary in 5/54 patients, CNS in 5 (9.3%), 2 of which were solely CNS. In the chemotherapy arm, these second relapses were extramedullary in 8/57 patients, CNS in 3 (5.3%), 2 of which were solely CNS. CD19-negative relapse was seen in 3 patients in the blinatumomab arm (3/54) and 1 patient in the chemotherapy arm (1/57) prior to any subsequent CD19-directed therapy (ie, after study therapy).
Conclusion
In children with high-risk first-relapse B-ALL, treatment with 1 cycle of blinatumomab vs chemotherapy before alloHSCT resulted in superior EFS and improved OS and MRD response rates, all independent of baseline MRD. The incidence of CD19-negative relapse after blinatumomab was low.
Keyword(s): CD19, Minimal residual disease (MRD), Stem cell transplant, Survival