Older patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) who were not good candidates for the standard treatment of intensive chemotherapy had a median overall survival (OS) of 6.5 years on an alternate regimen of dasatinib and blinatumomab.
These long-term results from the S1318 clinical trial will be presented at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego on December 9 (abstract 1499).
Anjali S. Advani, MD, a SWOG investigator at Cleveland Clinic Cancer Institute, led the study, with study co-chair Kristen O'Dwyer, MD, of the Wilmot Cancer Institute at the University of Rochester.
"These long-term results are encouraging and suggest that this regimen is an active regimen for the treatment of older patients with Ph+ ALL," said Dr. Advani, who will present the findings at the ASH meeting.
Treatment for Ph+ ALL typically includes tyrosine kinase inhibitors (TKIs) and intensive chemotherapy, but many patients age 65 or older cannot tolerate the side effects of the chemotherapy and are treated with TKIs plus corticosteroids. Median disease-free survival (DFS) times with this approach, however, have been short. More effective treatment regimens with less toxicity are needed.
The S1318 clinical trial, led by the SWOG Cancer Research Network, a clinical trials group funded by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), tested a combination treatment for these Ph+ patients that added immunotherapy with blinatumomab (a bispecific T-cell engager) to dasatinib (a TKI) and prednisone (a corticosteroid).
Initial S1318 results in Ph+ patients were presented at the 2021 ASH meeting 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 three-year OS and DFS. But longer follow-up was needed to learn whether the benefit would be durable.
The current ASH abstract presents long-term S1318 results in Ph+ patients, confirming the durability of the initial benefit. The median OS is 6.5 years, and with a median follow-up time of 4.3 years, median DFS had not yet been reached as of mid-2023.
The 24 eligible patients with Ph+ ALL on S1318 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 re-induction therapy with blinatumomab. Post-remission therapy consisted of blinatumomab and dasatinib, and maintenance therapy included prednisone and dasatinib.
Twenty-two of the 24 patients saw a complete remission (CR) of their disease on the combination treatment. Measurements of minimal residual disease (MRD), taken at day 28 of treatment, were available for 16 of those 22 patients. Six of these 16 patients (38%) were found to show no evidence of MRD at day 28.
Two patients experienced treatment-related non-hematologic Grade 4 toxicities during induction therapy, but no patients experienced Grade 4 or higher treatment-related non-hematologic toxicities during post-remission or maintenance therapy.
Study S1318 is sponsored by the NCI, led by SWOG, and conducted by the NIH-funded National Clinical Trials Network (NCTN).
The study is funded by the NIH/NCI through grants CA180888, CA180819, CA180820, and CA180821. Bristol Myers Squibb and Amgen Inc. provided support for S1318 through Cooperative Research and Development Agreements with NCI.
In addition to Drs. Advani and O'Dwyer, co-authors on this work include Anna Moseley, MS, SWOG Statistics and Data Management Center and Fred Hutchinson Cancer Center; Brent L. Wood, MD, PhD, University of Washington (during trial) and Children's Hospital Los Angeles (current); Jae Park, MD, Memorial Sloan Kettering Cancer Center; Matthew Wieduwilt, MD, University of California San Diego Moores Cancer Center (during trial) and University of Oklahoma (current); Deepa Jeyakumar, MD, UC Irvine Medical Center; George Yaghmour, MD, USC Norris Comprehensive Cancer Center; Ehab L. Atallah, MD, Froedtert and the Medical College of Wisconsin; Aaron T. Gerds, MD, MS, Cleveland Clinic Cancer Institute; Susan M. O'Brien, MD, UC Irvine Medical Center; Jane L. Liesveld, MD, University of Rochester; Megan Othus, PhD, SWOG Statistics and Data Management Center and Fred Hutchinson Cancer Center; Mark Litzow, MD, Mayo Clinic, Rochester; Richard M. Stone, MD, Dana-Farber Cancer Institute; Elad Sharon, MD, MPH, NCI Cancer Therapy Evaluation Program (CTEP); Cecilia C.S. Yeung, MD, Fred Hutchinson Cancer Center; Jerald P. Radich, MD, Fred Hutchinson Cancer Center; and Harry P. Erba, MD, PhD, Duke University Medical Center.
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