A study published in the Oct. 20 issue of the Journal of Clinical Oncology examined the effects of combination ibrutinib plus venetoclax in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).
“The treatment of chronic lymphocytic leukemia (CLL) has been revolutionized by targeted therapies that either inhibit proliferation (ibrutinib) or reactivate apoptosis (venetoclax). Both significantly improve survival in CLL and replace chemoimmunotherapy for many patients,” the study authors wrote. “However, individually, they rarely lead to eradication of measurable residual disease (MRD) and usually are taken indefinitely or until progression.”
The researchers reported the outcomes of the phase II CLARITY trial. The study’s primary outcome measure was elimination of MRD after 12 months of the combination treatment. Secondary outcomes included response per International Workshop on CLL criteria, safety, progression-free survival (PFS), and overall survival (OS). MRD negativity was defined as fewer than one CLL cell in 10,000 leukocytes.
Final analysis included 53 patients with 12 months of combination therapy. MRD negativity was attained in the blood of 28 (53%) patients and marrow of 19 (36%) patients. Most (n = 47, 89%) patients responded, and about half (n = 27, 51%) achieved full remission. Median follow-up was 21.1 months, at which time all patients were alive and there was one case of progression and one case of biochemical tumor lysis syndrome. Adverse events were considered mild and were most commonly neutropenia or GI-related.
The researchers stated in their conclusion, “We have demonstrated promising efficacy that indicates potent synergy between ibrutinib and venetoclax for inducing MRD-negative responses with manageable adverse effects. The observation that a significant proportion of patients experience MRD-negative remission indicates that this combination can be given for a limited period and then stopped after patients achieve a deep remission. This observation is critical before taking the MRD-guided approach into larger phase III trials. Whether the combination leads to permanent disease eradication in a subset of these patients remains to be seen.”