The following article features coverage from the American Society of Hematology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

The second-generation Bruton tyrosine kinase inhibitor tirabrutinib (ONO/GS-4059) showed promising efficacy in patients with treatment-naive (TN) or relapsed/refractory (RR) Waldenström macroglobulinemia (WM), according to early findings from a prospective, multicenter phase 2 study presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida.

“Although the follow-up time was relatively short, the results of this phase 2 study showed that tirabrutinib monotherapy is a highly effective treatment option for patients with TN and R/R WM, with a manageable safety profile,” reported lead author Wataru Munakata, MD, PhD, of the National Cancer Center Hospital in Tokyo, Japan, and coauthors, in the study abstract.

Twenty-seven patients (18 with TN and 9 with RR WM) with serum IgM of 500 mg/dL or higher, Eastern Cooperative Oncology Group (ECOG) performance status of at least 1, and normal end-organ function were enrolled in the study and administered tirabrutinib (480 mg once daily).

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At a median follow-up of 6.49 months, the independent review committee-assessed major response rate (IRC MRR, ≥ partial response [PR]) was 72.2% in patients with TN WM and 88.9% among patients with R/R WM, the researchers reported. IRC overall response rate (ORR) was 94.4% and 100% among patients with TN and R/R WM, respectively.

“The most common adverse events (AEs) at any grade were rash (44%), neutropenia (25.9%), and leukopenia (22.2%), of which most were grade 1 or 2,” the authors reported. Grade 3 of higher AEs were neutropenia (11.1%), leukopenia, lymphopenia (11.1%), atypical mycobacterial infection (7.4%), rash erythmatous, hegmatogenous retinal detatchment, erythema multiforme, and type 2 diabetes mellitus (all in 3.7%).

There were grade 4 instances of lymphopenia and neutropenia, but no grade 5 AEs or patient deaths. The severe AEs — transient ischemic attack (3.7% and rhegmatogenous retinal detachment (3.7%) were determined to be unrelated to treatment with tirabrutinib.

One patient discontinued tirabrutinib because of an atypical mycobacterial infection, and drug-related bleeding events happened in 3 patients (including 2 instances of epistaxis and 1 instance of mouth hemorrhage). Importantly, there was no drug-related atrial fibrillation observed.

Disclosure: Some of the authors disclosed financial relationships with the pharmaceutical industry. For a full list of disclosures, please refer to the original abstract.

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Munakata W, Sekiguchi N, Shinya R, et al. Phase 2 Study of Tirabrutinib (ONO/GS-4059), a Second-Generation Bruton’s Tyrosine Kinase Inhibitor, Monotherapy in Patients with Treatment-Naïve or Relapsed/Refractory Waldenström Macroglobulinemia. Presentation at: 2019 American Society of Hematology 61st Annual Meeting & Exposition; December 7-10; Orlando, Florida. Abstract 345.