ASH 2019 – Waldenström's macroglobulinemia: tirabrutinib shows high response


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

  • Tirabrutinib (ONO/GS-4059), a second-generation Bruton’s tyrosine kinase inhibitor shows a high response rate in patients with treatment-naïve (TN) or relapsed/refractory (R/R) Waldenström's macroglobulinemia, with a manageable safety profile.

Why this matters

  • Waldenström's macroglobulinemia is an incurable lymphoplasmacytic lymphoma with poor outcomes, but some favorable responses have been observed with the first FDA approved Bruton’s tyrosine kinase inhibitor ibrutinib. 

Study design

  • A prospective, multicenter phase 2 study of 27 patients (median age, 71 years) with TN (n=18) or R/R (n=9) Waldenström's macroglobulinemia. 
  • Patients received tirabrutinib 480 mg once daily until disease progression, unacceptable toxicity, or death. 
  • Primary endpoint: major response rate (MRR, ≥ partial response [PR]).
  • Secondary endpoint: overall response rate (ORR; ≥ minor response [MR]), time to major response (TTMR), duration of response (DOR), PFS, OS, and safety. 
  • Funding: Ono Pharmaceutical Co., Ltd.

Key results

  • The median follow-up duration was 6 months.
  • MRR was 77.8% (95% CI, 52.4%-93.6%) in TN and 88.9% (95% CI, 51.8%-99.7%) in R/R groups. 
  • ORR was 94.4% (95% CI, 72.7%-99.9%) in TN and 100% (95% CI, 66.4%-100.0%) in R/R groups.
  • Median DOR, PFS, and OS were not reached.
  • The most common any grade adverse events (AEs) were rash (41%), neutropenia (22%), and leukopenia (15%).
  • The most frequent grade ≥3 AEs were neutropenia (7.4%), leukopenia, lymphopenia, atypical mycobacterial infection, rash erythematous, and erythema multiforme (3.7% each).
  • No grade 4-5 AE was reported.

Limitations

  • Small study group.