Study Finds Immunotherapy Increases Three-Year Survival in Adults with B-Cell Precursor Acute Lymphoblastic Leukemia

Adults with B-cell precursor acute lymphoblastic leukemia (B-ALL) relapse, despite having negative minimal residual disease (MRD). A randomized phase 3 study found that adding the immunotherapy blinatumomab to standard chemotherapy significantly improved survival. The results, which were published in the New England Journal of Medicine, were striking: After three years, 85% of patients who received blinatumomab in addition to chemotherapy survived, compared to 68% survival among patients who received chemotherapy alone.

Background

“Our best chance of improving outcomes for adults with B-ALL is in the frontline setting,” says Anjali Advani, MD, Director of the Inpatient Leukemia Program at Cleveland Clinic Cancer Institute and co-author of the study. “Data has shown that intensifying chemotherapy doesn’t offer a benefit in adults with ALL, so the question was, could we add a novel agent to chemotherapy and improve outcomes for patients up front?”

Blinatumomab is a bispecific T-cell engager that targets CD19 surface antigens on B cells. It was already FDA approved and well tolerated for relapsed/refractory ALL as well as MRD positive B-ALL. The researchers set out to determine if the medication could offer a benefit as a frontline agent.

Study details

The trial included 224 patients ages 30 to 70 with newly diagnosed BCR::ABL-1 negative B-cell ALL who were MRD negative after induction chemotherapy. Trial participants were randomized into two groups. The control group received four cycles of consolidation chemotherapy while the experimental group received alternating cycles of blinatumomab and chemotherapy. For each blinatumomab cycle, patients received continuous infusion for a four-week period.

After this treatment, patients had the option to receive a stem cell transplant if their physician felt they were a good candidate for one. Patients in both groups received POMP maintenance therapy for approximately two years.

Study results

At a median follow-up at 43 months, researchers found notable improvements in survival among the experimental group. The overall survival was 85% in the experimental group vs. 68% in the control group. The three-year relapse-free survival was 80% in the experimental group and 66% in the control group.

“It’s notable that even among patients who are MRD negative, there is a significant improvement in relapse-free survival and overall survival with the addition of blinatumomab,” says Dr. Advani.

In terms of adverse events, the toxicity rates were as follows:

Primary side effects in the experimental group were neurologic system issues, which are common in some types of immunotherapies. In most instances, these adverse events could be managed.

What’s next

Based in part on preliminary data from this study, the FDA approved blinatumomab for use in adults and children with BCR:ABL1-negative B-ALL. The data spurred changes in NCCN guidelines as well as standards of care at many cancer institutes. “While the study has some limitations, the survival curves from it are very impressive,” says Dr. Advani.

Researchers are now looking to learn more about different patient populations and their response to immunotherapies. For example:

• Do older patients benefit from blinatumomab as much as younger patients?
• Do patients who are truly MRD negative need as many treatment cycles?
• Are there biologic subsets of this population that respond to this treatment better than others?

In addition, efforts are under way to ease the burden on patients while maintaining efficacy. Currently, blinatumomab is administered via pump at home in 28-day cycles. The medication manufacturer is studying whether subcutaneous administration may be an option for patients.