In the phase II SWOG 1318 trial reported in the Journal of Clinical Oncology, Advani et al found that blinatumomab induction and consolidation followed by maintenance with POMP (prednisone, vincristine, mercaptopurine, and methotrexate) produced good outcomes in patients aged ≥ 65 years with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (ALL).
Study Details
The study enrolled 29 eligible patients from National Clinical Trial Network sites between June 2015 and September 2017. Patients received blinatumomab induction (9 µg once daily on days 1–7 and 28 µg once daily on days 8–28) for one to two cycles until achievement of complete response or complete response with incomplete blood cell count recovery. They then received three cycles of blinatumomab consolidation (28 µg once daily on days 1–28) followed by 18 months of POMP maintenance. Intrathecal methotrexate was administered as central nervous system prophylaxis every 4 to 6 weeks for a total of eight doses. The primary objective was to estimate 3-year overall survival.
KEY POINTS
- Response was observed in 66% of patients, including in those with poor-risk cytogenetics.
- Estimated 3-year disease-free and overall survival rates were 37% and 37%.
Responses
Patients had a median age of 75 years (range = 66–84 years). The median bone marrow blast count percentage was 87%. Median follow-up was 3.14 years.
Complete response or complete response with incomplete blood cell count recovery was achieved in 19 of 29 patients (66%, 95% confidence interval [CI] = 46%–82%). Responses were achieved in 7 of 10 patients with poor-risk cytogenetics and in 3 of 5 with the Ph-like ALL gene signature. Among 13 responders with available measurable residual disease (MRD) data, 12 patients (92%) achieved MRD negativity (< 0.01%).
Kaplan-Meier estimated 3-year disease-free survival and overall survival rates were 37% (95% CI = 17%–57%) and 37% (95% CI = 20%–55%), respectively.
Adverse Events
The most common nonhematologic treatment-related grade 3 or 4 adverse events were hyperglycemia (14%), dyspnea (10%), hypertension (10%), and lung infection (7%). Grade 3 cytokine-release syndrome and grade 3 neurologic toxicity occurred in one patient each. Grade 3 or 4 treatment-related hematologic toxicities included decreased platelets (45%), decreased white blood cell count (38%), anemia (34%), and decreased lymphocytes (28%). Grade 3 febrile neutropenia occurred in 10%. One patient died of treatment-related respiratory failure.
The investigators concluded: “Blinatumomab was well tolerated and effective in the treatment of older patients with newly diagnosed [Ph-negative B-cell ALL], including patients with poor-risk cytogenetics. The 3-year disease-free survival and overall survival results are encouraging and suggest that this approach should be further explored.”
Anjali S. Advani, MD, of Cleveland Clinic, Taussig Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
