A time-limited, frontline combination of ibrutinib (Imbruvica) and venetoclax (Venclexta) shows to mobilize and clear chronic lymphocytic leukemia (CLL), leading to deep responses for patients who achieved undetectable minimal residual disease (MRD) status, according to results from the CAPTIVATE study. Currently, ibrutinib and venetoclax are approved as frontline single oral agent treatments.
The study, which includes contributions from several LRF grantees, Mantle Cell Lymphoma Consortium (MCLC) and Scientific Advisory Board (SAB) members, evaluated 164 CLL/small lymphocytic lymphoma (SLL) patients who received frontline treatment with ibrutinib plus venetoclax. Initial results showed the combination treatment led to undetectable MRD in 75 percent of patients. Patients with confirmed undetectable MRD at the end of the combination period were randomized to receive either further treatment with ibrutinib alone or a placebo. Patients with unconfirmed undetectable MRD were also randomized to receive ibrutinib alone or continued combination treatment.
Across all patient cohorts, the 30-month progression-free survival (PFS) rate from the time of initial treatment was greater than 95 percent (confirmed undetectable MRD group was 95.3 percent with placebo, 100 percent with ibrutinib; unconfirmed undetectable MRD group was 95.2 percent with ibrutinib, 96.7 percent with combination treatment). MRD status was improved with continued combined therapy versus an ibrutinib monotherapy for patients who did not achieve confirmed undetectable MRD.
The best overall undetectable MRD rates improved in bone marrow as well, from 32 percent after initial combination treatment to 42 percent with ibrutinib; and from 31 percent to 66 percent in patients who continued combination treatment. In peripheral blood, the undetectable MRD rate remained unchanged with ibrutinib; yet, it improved from 50 percent to 69 percent with combination treatment.
This study included contributions from LRF grantees Danelle F. James, MD, MAS (now with Pharmacyclics, LLC, an Abbvie Company, and Janssen Biotech, Inc.), and James M. Pagel, MD, PhD of Fred Hutchinson Cancer Research Center; Mantle Cell Lymphoma Consortium member Ian W. Flinn, MD, PhD of Sarah Cannon Research Institute/Tennessee Oncology; and past SAB member Thomas J. Kipps, Md, PhD of the University of California, San Diego/Moores Cancer Center.
More Updates from the 2020 American Society of Hematology Annual Meeting
Widely regarded as the premier event in malignant and non-malignant hematology, the virtual ASH Annual Meeting held from December 5-8, 2020 provided a critical forum for leading hematologists /oncologists to present their findings to over 20,000 of their peers.
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