A three-drug combination that put chronic lymphocytic leukemia into deep remission in a large group of patients.
A new Phase 2 clinical trial led by researchers at Dana-Farber Cancer Institute, which included patients with any subtype of CLL, found that a regimen of acalabrutinib , venetoclax , and obinutuzumab produced profound remissions in 89% of participants. The new group, which includes only high-risk chronic lymphocytic leukemia (CLL) patients, experienced a similar profound remission rate of 83%.
Study demonstrates effectiveness of three drugs in patients with lymphocytic leukemia.
The study’s lead author, Christine Ryan, of Dana-Farber, will present the findings at the American Society of Hematology (ASH) Annual Meeting.
The study, conducted at Dana-Farber, Beth Israel Deaconess Medical Center, Stamford Hospital and Lifespan Health System, Rhode Island, involves 68 patients with previously untreated CLL, 41 of whom have a mutation and/or or a deletion of the TP53 gene in their cancer 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) in a specific schedule that can continue for up to 16 cycles.
During study follow-up (35 months after the start of the therapy trial), 83 percent of high-risk patients had undetectable minimal residual disease (MRD) – no detectable CLL cells per 100,000 WBCs – in the bone marrow. 45% had the most profound measurable response to treatment: complete remission and undetectable MRD in the bone marrow. Overall, the researchers found that the treatment was well tolerated, with low rates of cardiovascular problems and infections. After nearly three years of follow-up, 93% of study participants were alive and free of presentationsno progression of the disease. The study in part supported the development of a large phase III study of the regimen for CLL patients without high-risk disease, which could lead to FDA approval. of the regulation of food and pharmaceutical products).
“Our data provide critical support for the use of this therapeutic trifecta in high-risk CLL patients,” says study senior author and principal investigator Matthew Davids of Dana-Farber.