TY - JOUR
T1 - Two-year outcomes of tirabrutinib monotherapy in Waldenström’s macroglobulinemia
AU - Sekiguchi, Naohiro
AU - Rai, Shinya
AU - Munakata, Wataru
AU - Suzuki, Kenshi
AU - Handa, Hiroshi
AU - Shibayama, Hirohiko
AU - Endo, Tomoyuki
AU - Terui, Yasuhito
AU - Iwaki, Noriko
AU - Fukuhara, Noriko
AU - Tatetsu, Hiro
AU - Iida, Shinsuke
AU - Ishikawa, Takayuki
AU - Iguchi, Daisuke
AU - Izutsu, Koji
N1 - Funding Information:
We thank the patients who participated and their supportive families for making this study possible. We also thank the medical professionals in the study sites. We are grateful to Dr. Kazuo Tamura (General Medical Research Center, Fukuoka University, Fukuoka, Japan) and Dr. Hirokazu Nagai (Nagoya Medical Center, Nagoya, Japan) for reviewing clinical data as members of the Efficacy and Safety Monitoring Committee. A medical written support was provided by Masatoshi Esaki, PhD, of Ono Pharmaceutical, Co., Ltd., and this study was funded by Ono Pharmaceutical.
Funding Information:
We thank the patients who participated and their supportive families for making this study possible. We also thank the medical professionals in the study sites. We are grateful to Dr. Kazuo Tamura (General Medical Research Center, Fukuoka University, Fukuoka, Japan) and Dr. Hirokazu Nagai (Nagoya Medical Center, Nagoya, Japan) for reviewing clinical data as members of the Efficacy and Safety Monitoring Committee. A medical written support was provided by Masatoshi Esaki, PhD, of Ono Pharmaceutical, Co., Ltd., and this study was funded by Ono Pharmaceutical.
Publisher Copyright:
© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
KW - Bruton's tyrosine kinase inhibitor
KW - Japanese
KW - Waldenström's macroglobulinemia
KW - phase II
KW - two-year follow-up
UR - http://www.scopus.com/inward/record.url?scp=85127592763&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85127592763&partnerID=8YFLogxK
U2 - 10.1111/cas.15344
DO - 10.1111/cas.15344
M3 - Article
C2 - 35332633
AN - SCOPUS:85127592763
SN - 1347-9032
VL - 113
SP - 2085
EP - 2096
JO - Cancer Science
JF - Cancer Science
IS - 6
ER -
