Phase 2 Study Shows Promise for Treating Older Adults with Ph-Negative B-ALL

Chemotherapy treatment has not proven effective for older adults with Philadelphia (Ph) chromosome-negative B-acute lymphoblastic leukemia (B-ALL). In a recent Phase 2, multi-site study, researchers found that using the monoclonal antibody blinatumomab (BLINCYTO®) followed by POMP (prednisone, vincristine, 6-mercapopurine and methotrexate) maintenance improved overall survival over traditional chemotherapy for older patients with newly diagnosed Philadelphia chromosome-negative B-cell acute ALL. Blinatumomab was well tolerated and effective, including in patients with poor-risk cytogenetics.

Study purpose

“Many older patients have issues tolerating high-dose chemotherapy,” says Anjali Advani, MD, national principal investigator, first author of the paper and staff physician in the Department of Hematologic Oncology and Blood Disorders and Director of the Inpatient Leukemia Program at Taussig Cancer Institute at Cleveland Clinic. “The study findings support the notion that many new immunotherapies are quite effective and have a low mortality rate. Our hope is that in the future we may not need to give older patients such high doses of chemotherapy due to the efficacy of antibody-based therapy.”

Study makeup

In this study of patients treated at National Clinical Trial Network sites, researchers evaluated blinatumomab as induction and consolidation therapy, followed by a combination of POMP maintenance chemotherapy. The study included patients aged 65 or older who were newly diagnosed with Ph chromosome-negative B-ALL. Patients received:

• Blinatumomab for one or two cycles until achieving complete remission or complete remission with incomplete count recovery
• Three cycles of consolidation with blinatumomab, followed by 18 months of POMP maintenance chemotherapy
• Eight doses of intrathecal methotrexate on a prophylaxis basis to protect the central nervous system

29 patients were enrolled, with a median age of 75 years and median bone marrow blast count at diagnosis of 87%. Cytogenetic risk was poor in 34% of patients, and 36% had the Ph-like ALL gene signature. 66% of patients achieved a complete response. Kaplan-Meier three-year disease free survival was 37%.

“Having this large cooperative group trial supports the premise that antibody-based therapy is safe and effective,” says Dr. Advani. Though randomized studies need to be conducted before this type of treatment becomes standard of care, Dr. Advani is optimistic that monoclonal antibody treatment will soon be used in the up-front setting.

Study findings

“The results of the study were better with this single agent than with traditional chemotherapy, but overall survival at three years was just 37 percent, so we’re working to improve upon that,” she says. Subsequent studies will evaluate sequencing of additional immunotherapies as a means to improve remission rates.