- 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.
- 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.
- 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.
- Limited sample size and follow-up.