R/R CLL/MCL: phase 1-1b results for ibrutinib+umbralisib

  • Davids MS & al.
  • Lancet Haematol
  • 14.12.2018

  • von David Reilly
  • Univadis Clinical Summaries
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Takeaway

  • In patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL), dual Bruton's tyrosine kinase (BTK) and phosphoinositide 3-kinase delta (PI3K-delta) inhibition with umbralisib and ibrutinib delivered high-level response and was well-tolerated.

Why this matters

  • This may be the first trial of combination BTK and PI3K-delta inhibition in B-cell malignancies.

Study design

  • Phase 1-1b study to investigate umbralisib+ibrutinib in 42 patients with R/R CLL (n=21) or MCL (n=21).
  • Median patient age, 68 years (range, 48-85 years).
  • Funding: TG Therapeutics; Leukemia and Lymphoma Society Therapy Accelerator Program.

Key results

  • Maximum tolerated dose of umbralisib was not identified; 800 mg /day was recommended for phase 2 study.
  • Grade 3-4 hematological malignancies were uncommon.
  • 17% of patients experienced grade 3-4 infections.
  • No cases of grade 3-4 colitis or pneumonitis.
  • Low incidence of immune-related toxicities.
  • 29% of patients experienced a serious adverse event.
  • Across all doses studied in patients with CLL:
    • 90% overall response rate (ORR).
    • 29% complete response (CR).
    • 62% partial response (PR).
  • Across all doses studied in patients with MCL:
    • 67% ORR.
    • 19% CR.
    • 48% PR.

Limitations

  • Limited sample size and follow-up.