Oncology Today with Dr Neil Love Chronic Lymphocytic Leukemia — An Interview with Prof Constantine Tam on Key Presentations from the 2025 ASH Annual Meeting
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Mar 10, 2026 Prof Constantine Tam, academic hematologist from Monash University, explains recent CLL datasets from ASH and what they mean for patient care. He discusses moving from continuous BTKi to time-limited oral doublets, challenges and practical tips for venetoclax delivery and ramp-up, the promise of somerotoclax for deeper MRD clearance, and strategies around BTKi selection, relapse management, CAR T timing, and future fixed-duration approaches.
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Sotoroclax Offers Stronger BCL2 Inhibition And Higher MRD
- Sotoroclax (someroloclax) is a more potent BCL2 inhibitor with tighter binding and shorter half-life compared to venetoclax.
- It can overcome some venetoclax-resistance BCL2 mutations and yields higher MRD clearance without worse toxicity.
Higher MRD With New BCL2 Improves Oral Doublets
- Upgrading BCL2 from venetoclax to someroloclax markedly increases MRD negativity rates, with oral doublets hitting >90% MRD versus ~50% with venetoclax doublets.
- Obinutuzumab skews peripheral blood MRD lower than bone marrow, complicating comparisons.
CL-17 Shows Comparable Early Outcomes But Different Long-Term Tradeoffs
- CL-17 provides randomized evidence that time-limited venetoclax–obinutuzumab and continuous BTKi yield similar early outcomes, but differences may emerge later.
- Continuous BTKi preserves an active drug on relapse, whereas relapsing after venetoclax often allows successful re-challenge.