Episode 164: CLL Updates Series, Pt. 1 – Frontline Therapy in 2026

Episode 164: CLL Updates Series, Pt. 1 – Frontline Therapy in 2026

This week we kick off a two-part update to our CLL series, covering what has changed in frontline management since our original episodes. Using the case of a 68-year-old man with newly diagnosed, symptomatic CLL, we revisit the essential steps before treatment: confirming an indication to treat, ruling out Richter's transformation, and risk stratification, with the history behind FISH cytogenetics, IGHV status, and the CLL-IPI. We then trace how continuous BTK inhibitors and fixed-duration venetoclax-obinutuzumab displaced chemoimmunotherapy, before digging into the trials reshaping practice in 2026: AMPLIFY, SEQUOIA Arm D, and CLL17. Along the way, we cover the open questions for TP53-aberrant disease and why MRD, although prognostic, is not yet a reliable guide for treatment decisions with novel agents. 

If you haven’t done so, be sure to check out our original CLL Series, as these updates will draw on concepts covered previously!