Blinatumomab improved survival in children with relapsed B-acute lymphoblastic leukemia (B-ALL) compared with standard chemotherapy, accordings to findings from a study presented by Brown et al at the 2019 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract LBA-1). Researchers say the results support blinatumomab as a new standard of care for patients with high- and intermediate-risk relapsed B-ALL who are preparing to receive a bone marrow transplant.

Blinatumomab is a bispecific T-cell engager (BiTE) antibody construct that binds specifically to CD19, a protein expressed on the surface of B cells, and CD3, a protein expressed on the surface of T cells.

“From past experience, our understanding is that bone marrow transplant is the therapy that gives these children and young adults the best chance of a cure,” said lead study author Patrick A. Brown, MD, of the Johns Hopkins Kimmel Cancer Center. “Based on our study, it appears that blinatumomab is a much more effective bridge to transplant for this patient population, leading to a much larger portion of patients who are actually able to receive a bone marrow transplant. We believe that is the reason for the striking improvement in survival among patients who received blinatumomab.”

Blinatumomab is currently approved by the U.S. Food and Drug Administration for use in patients with relapsed and refractory B-ALL, but this is the first trial to confirm its benefits in pediatric patients who have minimal residual disease (MRD) following an initial course of chemotherapy after relapse.

Methods

In the study, all patients first received 1 month of standard chemotherapy treatment. Researchers then identified 208 patients who were considered to have high- or intermediate-risk disease based on the timing of their relapse or the presence of MRD and randomly assigned these patients into one of two groups. One group received 2 months of blinatumomab therapy, while the control group received the standard course of 2 additional months of chemotherapy.

The researchers tracked disease-free survival, which was the trial’s primary endpoint, along with overall survival, ability to proceed to transplant, changes in MRD, and adverse events. Trial enrollment was stopped early after an interim analysis found the benefits of blinatumomab were substantial enough to establish it as a new standard of care.

Results

After a median follow-up of 1.4 years, patients receiving blinatumomab showed a significantly higher rate of disease-free survival (59%, compared to 41% in the control group), overall survival (79% vs 59%), and ability to proceed to transplant (73% vs 45%). Among patients with detectable MRD after the first month of chemotherapy, 79% of those receiving blinatumomab achieved undetectable MRD compared to 21% among those receiving chemotherapy alone.

Like previous studies, the trial showed blinatumomab had significantly fewer side effects than standard chemotherapy. Patients in the control group had higher rates of fever, infection, sepsis, and mucositis; four patients in this group died from the toxic effects of chemotherapy. Some patients receiving blinatumomab experienced some adverse events known to be associated with the drug, including cytokine-release syndrome, seizures, and other forms of nerve damage, all of which fully resolved. No patients who received blinatumomab died.

The researchers will continue to track enrolled patients to assess longer-term outcomes. Dr. Brown noted that the study findings establish blinatumomab as a new standard of care only for patients with the risk profiles examined in the study, not for lower-risk patients or those who have not experienced relapse. Further research is needed to examine the potential benefits of using immunotherapy earlier in the B-ALL treatment cycle and to find out whether blinatumomab therapy can be further optimized through combinations with other therapeutic approaches.

Disclosure: Amgen provided blinatumomab for the study under a Collaborative Research and Development Agreement with the National Cancer Institute. For full disclosures of the study authors, visit ash.confex.com.