Kerry A. Rogers, MD
The regimen of obinutuzumab (Gazyva), ibrutinib (Imbruvica), and venetoclax (Venclexta) can be safely given as initial therapy for chronic lymphocytic leukemia (CLL), according to preliminary results of a phase II trial of treatment-naïve patients.
, Rogers, assistant professor of internal medicine in the Division of Hematology at The Ohio State University Comprehensive Cancer Center, discussed the promise of the obinutuzumab, ibrutinib, and venetoclax triplet as a first-line treatment for patients with CLL.
OncLive: Can you discuss the initial results of the phase II treatment-naïve cohort?
: This phase Ib/II study of obinutuzumab, ibrutinib, and venetoclax in CLL is a way to study a chemotherapy-free combination. Generally, combination treatment in CLL has a very long tradition of success, including combinations with chemotherapy and CD20-targeted monoclonal antibodies, leading to very high rates of durable response. However, the side effects of chemotherapy are very difficult for a lot of patients, and there are some long-term side effects.
Important things that we have yet to see out of this study are the primary endpoint, which is the rate of MRD-negative CR after treatment. This is a time-limited treatment strategy of 14 months, similar to some chemoimmunotherapy regimens. It will be exciting to see what all of the end-of-treatment responses are, because that is when patients have stopped taking the drugs. The progression-free survival will also be very important.
Were there any toxicities that should be noted?
Most of the toxicities were consistent with what has already been reported with the 3 individual drugs. The most common nonhematologic AE was infusion-related reactions from obinutuzumab. Then, we saw bruising, arthralgia, hypertension, and side effects that are known for ibrutinib. The main higher-grade AEs were hematologic, with a lot of high-grade neutropenia. That is probably because all of the drugs in the study can cause neutropenia, so those are more specific to the combination.
In the treatment-naïve patients, which was what this cohort was, we actually did not see a lot of complications with neutropenia. We did have 1 person who got neutropenic colitis and bowel perforation that discontinued treatment, and subsequently died months later of late complications. It is a regimen that had substantial toxicity for at least 1 individual.
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