SOHO State of the Art Updates and Next Questions | Venetoclax + Obinutuzumab Therapy in Chronic Lymphocytic Leukemia.

Abstract

In the past decade, the treatment paradigm for chronic lymphocytic leukemia (CLL) has markedly shifted from traditional chemoimmunotherapy towards targeted therapies.¹ A fixed-duration, targeted regimen with venetoclax, a potent oral BCL-2 inhibitor, combined with obinutuzumab, a glycoengineered type II anti-CD20 monoclonal antibody (Ven-Obi), has become the standard to beat for time-limited therapy in CLL. Ven-Obi allows for the rapid induction of remissions with high rates of undetectable minimal residual disease (uMRD) in patients across different treatment settings. This strategy enables the discontinuation of therapy while maintaining treatment-free remissions for several years in many patients. With up to 6-year data now available from the pivotal phase 3 trial of this combination in CLL, this review aims to examine the evolving role of this strategy in CLL management, including updated data for safety and efficacy in randomized trials in both the frontline and relapsed/refractory (R/R) settings. We also explore real-world data for this combination, and review related issues, such as MRD monitoring, the potential for venetoclax retreatment or consolidative strategies and evaluate ongoing trials comparing this regimen as a standard of care control arm versus novel (including all-oral) therapeutic combinations.