Fixed-Duration Venetoclax Regimens Match Continuous Ibrutinib in First-Line CLL

Overview

• In a prospective trial of 909 untreated adults with CLL, patients were randomized to continuous ibrutinib, 12 cycles of venetoclax plus obinutuzumab, or three cycles of ibrutinib followed by 12 cycles of venetoclax.
• At a median 34 months of follow-up, progression-free survival was similar across arms (ibrutinib 81.0%, venetoclax–obinutuzumab 81.1%, ibrutinib→venetoclax 79.4%), meeting the prespecified non-inferiority endpoint.
• Overall response and overall survival were comparable (ORR 84.2%–88.5%; OS 91.5%–96.0%), but complete responses were far higher with fixed-duration therapy (51.5% and 46.2% vs 8.3%).
• Undetectable MRD was achieved in the venetoclax-based arms (blood 73% and 62%; marrow 62% and 40%), whereas no patients on continuous ibrutinib reached undetectable MRD.
• Adverse-event rates were broadly similar, with more cardiovascular events on ibrutinib and higher severe infection risk and shorter PFS in aggressive CLL linked to obinutuzumab; the investigator-initiated study (University of Cologne) was published in NEJM, presented at ASH, and will continue follow-up with planned biomarker studies.