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Results of a phase 3 study presented at ASH 2019 are suggesting blinatumomab was more effective than chemotherapy as a post-reinduction therapy in high and intermediate risk first relapse of b-acute lymphoblastic leukemia.
Patrick Brown, MD
Results of a phase 3 trial comparing blinatumomab versus chemotherapy as post-reinduction therapy in high- and intermediate-risk (HR/IR) first relapse of B-acute lymphoblastic leukemia (B-ALL) in children and adolescents revealed blinatumomab demonstrated superior efficacy and tolerability than standard chemotherapy alone.
Presented at the American Society of Hematology (ASH) 2019 annual meeting by Patrick Brown, MD, of the Division of Pediatric Oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, data from the study suggest blinatumomab use resulted in fewer and less severe toxicities, higher rates of minimal residual disease (MRD) response, greater likelihood of proceeding to allogeneic hematopoietic stem cell transplant (HSCT) and improved disease-free, and overall survival.
“Blinatumomab is superior to chemotherapy as a post-reinduction consolidation prior to transplant,” Brown said. “This is due to fewer and less severe toxicities, higher rates of MRD response, greater likelihood of proceeding to transplant, and improved disease-free and overall survival.”
In an effort to compare disease-free survival rates of HR/IR first relapse B-ALL patients between the ages of 1 and 30 years old, investigators conducted a randomized trial following re-induction chemotherapy where patients received either 2 intensive chemotherapy blocks or 2, 4-week blocks of blinatumomab. For the purpose of the current analyses, patients with 25% or greater marrow blasts after block 1 were ineligible for randomization.
A total of 208 patients were included in the study, of which 103 were randomized to the control arm of the study and 105 were randomized to receive blinatumomab. Investigators noted baseline characteristics between the two groups were comparable.
The intent-to-treat 2-year disease-free survival was 41.0 ± 6.2% for the control arm versus 59.3 ± 5.4% for the blinatumomab (P=0.05, 1-sided per pre-specified statistical plan). The intent-to-treat overall survival was 59.2 ± 6.0% in the control group versus 79.4 ± 4.5% for the blinatumomab group (p=0.005, 1-sided).
In patients with detectable MRD at the completion of Block 1 of chemotherapy, 21% of patients in the control group and 79% of patients receiving blinatumomab achieved undetectable MRD after Block 2. Additionally, observed rates of MRD response were similar with Block 3 or blinatumomab cycle 2.
Investigators pointed out post-induction death occurred in 4 patients in the control group, but there were zero instances of death in the blinatumomab group (P=0.05). In regard to adverse events, investigators noted relative rates of febrile neutropenia, infections, sepsis, and mucositis were higher for Block 2/3 in the control group compared to blinatumomab cycle 1/2.
In patients receiving blinatumomab, the rate of blinatumomab-related adverse events in cycle 1/2 were 22%/1% for cytokine release syndrome, 4%/0% for seizures, and 14%/11% for other neurotoxicity. Investigators noted all blinatumomab-related adverse events were fully resolved.
When examining the rate of patients successfully transiting from randomization to HSCT, investigators observed varying differences in success rates between the two groups. In the control group, just 45% of patients proceed to HSCT compared to 73% of patients in the blinatumomab group (P<0.0001).
This study, titled “A Randomized Phase 3 Trial of Blinatumomab Vs. Chemotherapy As Post-Reinduction Therapy in High and Intermediate Risk (HR/IR) First Relapse of B-Acute Lymphoblastic Leukemia (B-ALL) in Children and Adolescents/Young Adults (AYAs) Demonstrates Superior Efficacy and Tolerability of Blinatumomab: A Report from Children’s Oncology Group Study AALL1331,” was presented at ASH 2019.