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While hardly groundbreaking, the four-year follow-up data of the ELEVATE-TN trial affirms our confidence that acalabrutinib is a strong choice for frontline therapy in CLL.
The trial design was such that patients received Acalabrutinib ± Obinutuzumab (A±O) or Obinutuzumab + Chlorambucil (O+Clb). Crossover to acalabrutinib (A) monotherapy was permitted in pts who progressed on O+Clb. This was the correct and ethical way to run the trial and CLL Society applauds the trialists. Progression-free survival (PFS), overall response rate (ORR), overall survival (OS), and safety were evaluated.
535 treatment-naïve patients were enrolled. Average age was 70. Nine percent had del(17p).
At a median follow-up of 46.9 months, the median PFS was not reached for A+O and A pts versus 27.8 months for O+Clb patients. Estimated 48-month PFS rates were 87% for A+O, 78% for A, and 25% for O+Clb.
ORR was significantly higher with A+O (96.1%) versus O+Clb (82.5); ORR with A alone was 89.9%.
27% of the A+O arm achieved a complete remission (CR) compared to 12% with O+Clb and 11% with A alone.
Discontinuation rates were 25.1% (A+O), interestingly a slightly higher 30.7% for acalabrutinib alone and 22.6% (O+Clb).
Adverse events were as expected with diarrhea and headaches in about four out of ten and bleeding, usually not serious in a little less than half, in both arms that included A. Low neutrophils, (neutropenia), were seen in one third of the A+O arm, but that was fewer than the 45% seen with O+Clb.
We expected A with or without O to be a significant improvement over O+Clb. This confirms our expectations that Acalabrutinib ± Obinutuzumab has good efficacy and tolerability as a frontline therapy in CLL. It should also put the final kibosh on the use of O+Clb for treatment naïve CLL and as a comparator in any clinical trial. The use of chlorambucil based therapies in CLL should be retired.
Here is the link to the ASCO 2021 abstract that provides much finer details.
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Stay strong. We are all in this together.
Brian Koffman MDCM (retired) MS Ed
Co-Founder, Executive VP and Chief Medical Officer
CLL Society, Inc.