Older patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL) who were not candidates for the standard treatment of intensive chemotherapy had a median overall survival of 6.5 years on an alternative regimen of dasatinib and blinatumomab, according to long-term results from the SWOG 1318 trial presented at the 2023 ASH Annual Meeting & Exposition (Abstract 1499).
Anjali S. Advani, MD, a SWOG investigator at Cleveland Clinic Cancer Institute, led the study with co-chair Kristen O’Dwyer, MD, of the Wilmot Cancer Institute at the University of Rochester.
Anjali S. Advani, MD
“These long-term results are encouraging and suggest that this regimen is an active regimen for the treatment of older patients with Philadelphia chromosome–positive ALL,” said Dr. Advani, who presented the findings at ASH.
Treatment for Philadelphia chromosome–positive ALL typically includes tyrosine kinase inhibitors and intensive chemotherapy, but many patients aged 65 or older cannot tolerate the side effects of the chemotherapy and are treated with tyrosine kinase inhibitors plus corticosteroids. Median disease-free survival with this approach, however, has been short. More effective treatment regimens with less toxicity are needed.
SWOG 1318
The SWOG 1318 clinical trial tested a combination treatment for these Philadelphia chromosome–positive patients with ALL that added immunotherapy to blinatumomab, a bispecific T-cell engager, to dasatinib, a tyrosine kinase inhibitor, and prednisone, a corticosteroid.
Initial results from the study were presented at the 2021 ASH Annual Meeting & Exposition, and demonstrated that the combination was well tolerated by these patients and was efficacious, with a high rate of complete remission and promising estimates for 3-year overall and disease-free survival. But longer follow-up was needed to learn whether the benefit would be durable.
Data presented at the 2023 ASH Annual Meeting & Exposition included long-term SWOG 1318 results in Philadelphia chromosome–positive patients with ALL, confirming the durability of the initial benefit. The median overall survival was 6.5 years, and with a median follow-up of 4.3 years, median disease-free survival had not yet been reached as of mid-2023.
The 24 eligible patients with Philadelphia chromosome–positive ALL in SWOG 1318 were all newly diagnosed with the disease. All received initial induction therapy with dasatinib and prednisone. If their disease did not go into complete remission, they received reinduction therapy with blinatumomab. Postremission therapy consisted of blinatumomab and dasatinib, and maintenance therapy included prednisone and dasatinib.
Twenty-two of the 24 patients had complete remission of their disease on the combination treatment. Measurements of measurable residual disease (MRD), taken at day 28 of treatment, were available for 16 of those 22 patients; 6 of these 16 patients (38%) were found to show no evidence of MRD at day 28.
Two patients experienced treatment-related nonhematologic grade 4 toxicities during induction therapy, but no patients experienced grade 4 or higher treatment-related nonhematologic toxicities during post-remission or maintenance therapy.
Disclosure: Study S1318 is sponsored by the National Cancer Institute (NCI), led by SWOG, and conducted by the National Institutes of Health–funded National Clinical Trials Network (NCTN). Bristol Myers Squibb and Amgen Inc. provided support for SWOG 1318 through Cooperative Research and Development Agreements with NCI. For full disclosures of the study authors, visit ash.confex.com.
