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Fixed-Duration CLL Regimens Match Continuous Therapy as Chemo-Free Combo Beats Chemo in Ph+ ALL

Phase III data highlight deeper molecular remissions with targeted regimens, signaling a shift toward finite or chemo-free strategies.

Overview

  • In a randomized CLL trial of 909 patients with 34 months’ median follow-up, progression-free survival was about 81% across all arms, meeting non-inferiority for fixed-duration venetoclax-based combinations versus continuous ibrutinib.
  • Fixed-duration combinations produced far higher complete responses and undetectable MRD than continuous ibrutinib, including 51.5% and 46.2% CR rates and up to 73% MRD negativity in blood.
  • Safety signals varied by approach, with more cardiovascular events on prolonged ibrutinib and higher severe infections associated with obinutuzumab in aggressive CLL, prompting continued follow-up.
  • In newly diagnosed Ph+ ALL (n=236), ponatinib plus blinatumomab achieved 87% event-free survival versus 71% with imatinib plus chemotherapy at a 23-month median follow-up and reduced deaths to 3.5% from 10%.
  • The chemo-free ALL regimen yielded 94% complete remission and up to 80% MRD negativity after five cycles, incorporated crossover for MRD-positive controls, and was presented at ASH as the CLL study was simultaneously published in NEJM.