Two‐year outcomes of tirabrutinib monotherapy in Waldenström's macroglobulinemia. Issue 6 (6th April 2022)

• Record Type: Journal Article
• Authors: Sekiguchi, Naohiro; Rai, Shinya; Munakata, Wataru; Suzuki, Kenshi; Handa, Hiroshi; Shibayama, Hirohiko; Endo, Tomoyuki; Terui, Yasuhito; Iwaki, Noriko; Fukuhara, Noriko; Tatetsu, Hiro; Iida, Shinsuke; Ishikawa, Takayuki; Iguchi, Daisuke; Izutsu, Koji
• Is Part Of: Cancer science. Volume 113:Issue 6(2022)
• Page Start: 2085
• Page End: 2096
• Publication Date: 2022-04-06
• Subjects: Bruton's tyrosine kinase inhibitor -- Japanese -- phase II -- two‐year follow‐up -- Waldenström's macroglobulinemia; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.15344
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract: The phase II study of tirabrutinib monotherapy at a daily dose of 480 mg under fasting conditions for treatment‐naïve and relapsed/refractory Waldenström's macroglobulinemia (ONO‐4059‐05 study) demonstrated a promising efficacy and tolerable safety profile. We conducted an unplanned analysis with a median follow‐up of 24.8 months to update the efficacy and safety results and to report patient‐reported quality of life. Of 27 enrolled patients, 22 patients continued receiving the study drug. The major response assessed by an independent review committee was observed in 25 patients (93%), including one and five patients who newly achieved complete response and very good partial response, respectively, after the primary analysis. The progression‐free and overall survival rates at 24 months were 92.6% and 100%, respectively. Serum IgM levels in all patients except one declined and were maintained at low levels, although transient increases occurred after temporal interruption of the study drug. The disease‐related symptoms including recurrent fever and hyperviscosity mostly disappeared. Health‐related quality of life, assessed by cancer‐specific questionnaires, was mostly maintained. Grade 3–4 neutropenia, lymphopenia, and leukopenia were newly recognized in three, two, and one patient, respectively. Grade 3 treatment‐related hypertriglyceridemia was also recognized. Nine patients experienced grade 1–2 bleeding events (33%), one patient experienced grade 2 treatment‐related atrial fibrillation, and one patient experienced grade 1 treatment‐related hypertension. Treatment‐related skin adverse events were observed in 14 patients (52%). Taken together, tirabrutinib has durable efficacy with an acceptable safety profile for treatment‐naïve and refractory/relapsed Waldenström's macroglobulinemia. Abstract : Here, we present an update of the efficacy and safety results with a median follow‐up of 24.8 months in a phase II study of tirabrutinib monotherapy for treatment‐naïve and relapsed/refractory Waldenström's macroglobulinemia. The major response was observed in 25 (93%) out of 27 enrolled patients, including one complete response and eight very good partial responses. Nine patients experienced grade 1–2 bleeding events, and one patient each experienced grade 2 treatment‐related atrial fibrillation and grade 1 treatment‐related hypertension.