NEW ORLEANS – A three-drug combination that sent chronic lymphocytic leukemia (CLL) into deep remissions in a broad group of patients in a clinical trial is highly effective in patients with high-risk forms of the disease, a new, phase 2 clinical trial led by Dana-Farber Cancer Institute investigators indicates.
The initial cohort of the trial, which included patients with any subtype of CLL, found that a regimen of acalabrutinib, venetoclax, and obinutuzumab produced deep remissions in 89% of participants. The new cohort, which exclusively included patients with high-risk CLL, found a similar deep-remission rate of 83%.
The study's lead author, Christine Ryan, MD, of Dana-Farber, will present the findings at the American Society of Hematology (ASH) Annual Meeting.
The trial, conducted at Dana-Farber, Beth Israel Deaconess Medical Center, Stamford (Conn.) Hospital, and Lifespan Health System, in Rhode Island, involves 68 patients with previously untreated CLL, 41 of whom have a mutation and/or deletion in the TP53 gene in their tumor cells – an abnormality associated with an aggressive form of the disease. Patients are treated with acalabrutinib (a targeted drug), obinutuzumab (an antibody therapy), and venetoclax (a targeted agent) on a specified schedule that can continue for up to 16 cycles.
At a median follow-up of 35 months, 83% of the high-risk patients had undetectable minimal residual disease (MRD) – no detectable CLL cells per 100,000 white blood cells – in their bone marrow. And 45% had the deepest measurable response to the treatment: complete remission and undetectable MRD in the bone marrow.
Overall, the treatment was well-tolerated, researchers found, with low rates of cardiovascular problems and infections. After nearly three years of follow-up, 93% of the trial participants were alive with no advance of their disease. The study has in part supported the development of a large, phase III trial of the regimen for patients with CLL without high-risk disease that has the potential to lead to FDA approval of the regimen.
"Our data provide foundational support for using this triplet therapy in patients with high-risk CLL patients," says study senior author and principal investigator Matthew Davids, MD, MMSC, of Dana-Farber.
Funding for the trial is from Astra-Zeneca and Dr. Davids NIH 1R01CA266298-01A1 award. Additional drug supply is provided by Genentech and AbbVie.
Ryan will present her group’s findings on Saturday, Dec. 10 at 4:15pm CST.
Complete details on Dana-Farber’s activities at ASH are available online at www.dana-farber.org/ash.
About Dana-Farber Cancer Institute
Dana-Farber Cancer Institute is one of the world’s leading centers of cancer research and treatment. Dana-Farber’s mission is to reduce the burden of cancer through scientific inquiry, clinical care, education, community engagement, and advocacy. Dana-Farber is a federally designated Comprehensive Cancer Center and a teaching affiliate of Harvard Medical School.
We provide the latest treatments in cancer for adults through Dana-Farber Brigham Cancer Center and for children through Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. Dana-Farber is the only hospital nationwide with a top 5 U.S. News & World Report Best Cancer Hospital ranking in both adult and pediatric care.
As a global leader in oncology, Dana-Farber is dedicated to a unique and equal balance between cancer research and care, translating the results of discovery into new treatments for patients locally and around the world, offering more than 1,100 clinical trials.