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.


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“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.

Read more of Cancer Therapy Advisor‘s coverage of ASH’s annual meeting by visiting the conference page.

Reference

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.