ASH 2019 – Waldenstrom’s macroglobulinemia: idelalisib+obinutuzumab shows activity


  • W. Todd Penberthy, Ph.D.
  • Univadis
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Takeaway

  • Idelalisib plus obinutuzumab shows clinical activity with an objective response rate of 90% in patients with relapsed/refractory Waldenstrom’s macroglobulinemia.

 Why this matters

  • Waldenstrom’s macroglobulinemia continues to have poor outcomes despite recent FDA approval of tyrosine kinase inhibitor ibrutinib. 
  • Idelalisib, a phosphatidylinositol-3-kinase pathway inhibitor, recently demonstrated an objective response rate of 80%.
  • This is the first study to evaluate a chemotherapy-free novel combination of idelalisib and obinutuzumab.

Study design

  • Interim analysis of phase 2 Filo trial.
  • 49 patients with relapsed/refractory Waldenstrom’s macroglobulinemia received idelalisib 150 mg twice daily and obinutuzumab titrated to 1000 mg for a total of 6 28-day cycles during the induction phase.
  • Idelalisib was continued during the maintenance phase for up to 2 years.
  • Funding: Janssen.

Key results

  • Median follow-up was 18.3 (range, 14.9-23) months.
  • The overall response rate was 90% and the major response rate was 76% (very good partial response, 8%; partial response, 68%; minimal response, 14%).
  • Median PFS was 25.2 months. 
  • 1-year and 2-year OS was 98% (95% CI, 94%-100%) and 85% (95% CI, 69%-100%), respectively. 
  • Median duration of response was 21.8 months.
  • 35 patients experienced ≥1 grade ≥3 adverse events or serious adverse events.
  • Most frequent adverse events were hepatotoxicity, diarrhea, infections, skin disease, neutropenia, anemia, and thrombopenia.
  • The study is ongoing in 29 patients who entered the maintenance phase.

Limitations

  • No comparator.
  • The findings need confirmation in the final analysis.