Patrick A. Brown, MD
Blinatumomab (Blincyto) as post-reinduction consolidation therapy before hematopoietic stem cell transplantation (HSCT) improved disease-free survival (DFS) and overall survival (OS) by approximately 20% compared with intensive chemotherapy in pediatric and adolescent and young adult (AYA) patients with high- or intermediate-risk of first relapse of B-cell acute lymphoblastic leukemia (B-ALL), according to results presented at the 2019 ASH Annual Meeting.1
In the randomized, phase III AALL1331 trial (NCT02101853), which was conducted by the Children’s Oncology Group, results showed that the 2-year disease-free survival (DFS) was 59.3+
5.4% with blinatumomab compared with 41.0+
6.2% with those who received intensive chemotherapy (P
= .050) at a median follow-up of 1.4 years.
Additionally, the OS at 2 years was 79.4+
4.5% and 59.2+
6.0% with blinatumomab and chemotherapy, respectively (P
“For children, adolescents, and young adults who have a first relapse of B-lineage ALL that is either early or [minimal residual disease (MRD)]–positive after the first month [of chemotherapy], blinatumomab is superior to chemotherapy as post-reinduction consolidation prior to transplant,” Patrick A. Brown, MD, director of the Pediatric Leukemia Program, and associate professor of oncology at Johns Hopkins Medicine, said in a press conference during the meeting.
“This is due to fewer and less severe toxicities, higher rates of MRD response, greater likelihood of proceeding to transplant, and improved DFS and OS. Thus, blinatumomab constitutes a new standard of care in this setting.,” he explained.
Cure rates for pediatric and AYA ALL are high; however, relapse occurs in approximately 15% of patients. This leads to poor survival outcomes, especially in those that occur within 3 years of diagnosis or when the patient’s relapse is still MRD-positive after the first month of chemotherapy. Standard options for this specific population include intensive chemotherapy followed by transplant.
Blinatumomab is an anti-CD19 bispecific T-cell engager that is currently approved by the FDA for the treatment of adult and pediatric patients with relapsed/refractory B-cell precursor ALL, as well as adult and pediatric patients with B-cell precursor ALL in first or second complete remission with MRD ≥0.1%.
In the AALL1331 trial, investigators sought to determine whether substitution blinatumomab for intensive consolidation chemotherapy improves survival in first relapse of pediatric and AYA B-ALL. A total 208 patients who were between the ages 1 and 30, received 1 month of induction chemotherapy, and had early or late relapse with high levels of MRD were randomized to either a control arm of 2 blocks of intensive chemotherapy (n = 103) or 2 cycles of blinatumomab (n = 105) and then went onto HSCT.
Investigators initially planned to enroll 222 patients. However, randomization was halted at 208 patients; in September 2019, a Data Safety Monitoring Committee determined that the blinatumomab arm was superior based on better survival and MRD clearance as well as less toxicity.2
To be eligible for enrollment, patients must have had an ECOG performance score of 0 to 2 and had no prior stem cell transplant or rescue or prior treatment with blinatumomab. Patients with Philadelphia chromosome–positive disease were excluded from enrollment.
The primary endpoint was DFS of high- and intermediate-risk patients with B-ALL at first relapse; secondary endpoints include MRD clearance, adverse events (AEs), and bridge to transplant.
Additional data showed that MRD clearance was improved with blinatumomab compared with the end of chemotherapy block 1 (P
= .65) and end of chemotherapy block 2/blinatumomab cycle 1 (P
<.0001) and end of chemotherapy block 3/blinatumomab cycle 2 (P
Grade ≥3 AEs, including febrile neutropenia, infection, sepsis, and mucositis, were significantly higher with chemotherapy than blinatumomab (P
Moreover, more patients on blinatumomab had a greater ability to successfully bridge to transplant than those on intensive chemotherapy at each treatment point: those who started chemotherapy block 2/were on cycle 1 of blinatumomab (94% vs 97%; P
= .5), on chemotherapy block 3/cycle 2 of blinatumomab (56% vs 79%; P
= .0008), and went on to transplant (45% vs 73%; P