Efficacy and safety of ibrutinib in Japanese patients with relapsed or refractory mantle cell lymphoma.
In this multicenter, single-arm, phase II study, the efficacy and safety of ibrutinib were examined in Japanese patients with relapsed or refractory mantle cell lymphoma (MCL). Patients (age ≥20 years) with relapsed or refractory MCL who had progressed after receiving at least one prior treatment regimen, were enrolled. Patients were treated with oral ibrutinib (560 mg once daily; 28-day cycle) until disease progression (or relapse), unacceptable toxicity, or study end. The primary end-point was overall response rate. Secondary end-points included duration of response (DOR), time to response, progression-free survival (PFS), overall survival, and safety. Of the 16 patients who received treatment, 5 patients discontinued the study (progressive disease, 4; sepsis, 1). Median duration of ibrutinib exposure was 6.5 months (range, 2.8-8.3 months). The overall response rate was 87.5% (90% confidence interval, 65.6-97.7; complete response = 2 [12.5%]; partial response = 12 [75.0%]). Median time to response for all responders (n = 14) was 1.8 months (range, 0.7-5.3 months). The median DOR and PFS were not estimable due to censoring (range: DOR, 1.1-6.4+ months; PFS, 2.8-8.0+ months). Overall survival data were immature due to the limited observation period. A total of 8/16 patients (50%) had at least one grade 3 adverse event (AE), and 5 (31.3%) patients reported serious AEs. The most commonly reported AEs were diarrhea and stomatitis (37.5% each), platelet count decrease (31.3%), and anemia (25%). Overall, orally administered single agent ibrutinib was efficacious with an acceptable safety profile in Japanese patients with relapsed or refractory MCL. Clinical trial registration NCT02169180 (ClinicalTrials.gov).
Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
Dai
D
Maruyama
Department of Hematology, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
Hirokazu
H
Nagai
Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Noriko
N
Fukuhara
Department of Hematology and Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Toshiyuki
T
Kitano
Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan.
Takayuki
T
Ishikawa
Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
Hirohiko
H
Shibayama
Department of Hematology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
Ilseung
I
Choi
Department of Hematology Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
Kiyohiko
K
Hatake
Department of Hematology and Oncology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan.
Toshiki
T
Uchida
Department of Hematology and Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Momoko
M
Nishikori
Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan.
Tomohiro
T
Kinoshita
Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan.
Yoshihiro
Y
Matsuno
Janssen Pharmaceutical K.K., Tokyo, Japan.
Tomoaki
T
Nishikawa
Janssen Pharmaceutical K.K., Tokyo, Japan.
Satoko
S
Takahara
Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
Kensei
K
Tobinai
D000225:Adenine / Q000031:analogs & derivatives; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010880:Piperidines; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D019233:Retreatment; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D000225:Adenine
Efficacy; ibrutinib; mantle cell lymphoma; overall response rate; safety