ASCO 2019 — Acalabrutinib+obinutuzumab delivers high response in CLL


  • David Reilly
  • Oncology Conference reports
Access to the full content of this site is available only to registered healthcare professionals. Access to the full content of this site is available only to registered healthcare professionals.

Takeaway

  • Acalabrutinib+obinutuzumab demonstrated high-level response with minimal grade 3-4 adverse events (AEs) at 3-year follow-up in patients with treatment-naive or relapsed/refractory chronic lymphocytic leukemia (CLL).

Why this matters

  • Acalabrutinib monotherapy has previously demonstrated >93% objective response rate (ORR) in CLL.

Study design

  • 3-year follow-up of a phase 1b/2 study to investigate acalabrutinib+obinutuzumab in treatment-naive (n=19) and relapsed/refractory (n=26) CLL.
  • Median patient age, 61 (range, 42-76) years.
  • 53% of treatment-naive patients and 50% of those with relapsed/refractory disease had bulky disease.
  • Funding: Acerta Pharma.

Key results

  • Responses:
    • Treatment-naive group: 95% ORR; 31.6% complete response (CR); 63.2% partial response (PR).
    • Relapsed/refractory group: 92% ORR; 7.7% CR; 84.6% PR.
  • PFS:
    • Treatment-naive group at 39 months: 94.4% (95% CI, 66.6-99.2).
    • Relapsed/refractory group at 42 months: 72.7% (95% CI, 43.8-88.4).
  • Minimal residual disease (MRD) in bone marrow:
    • Treatment-naive group: 26%.
    • Relapsed/refractory group: 15%.
  • MRD negativity in peripheral blood was durable.
  • Incidence of grade 3-4 adverse events was minimal, with a 2% discontinuation rate. 

Limitations

  • Bone marrow biopsies were only performed to confirm CR in patients with MRD negativity in peripheral blood; some CRs may have therefore have been classed as PRs.  

Expert comment

  • Matthew S. Davids, MD, associate director of the CLL Center at Dana-Farber Cancer Institute and assistant professor of medicine at Harvard Medical School, Boston, Massachusetts, noted that the acalabrutinib regimen described requires continuous therapy to maintain response and mentioned a study in which he is involved that aims to find whether the addition of venetoclax to the regimen may enable a fixed-duration regimen.