Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002.
Purpose Few treatment options exist for adult T-cell leukemia/lymphoma (ATL), and the prognosis for this disease is poor. A phase I study of lenalidomide demonstrated preliminary antitumor activity in patients with relapsed ATL. The current phase II study evaluated the efficacy and safety of lenalidomide monotherapy in patients with relapsed or recurrent ATL. Patients and Methods Patients 20 years of age or older with acute, lymphoma, or unfavorable chronic subtype ATL, who had received one or more prior anti-ATL systemic chemotherapy and achieved stable disease or better on their last anti-ATL therapy with subsequent relapse or recurrence, were eligible. Patients received oral lenalidomide 25 mg/d continuously until disease progression or unacceptable toxicity. The primary end point was overall response rate; secondary end points included safety, tumor control rate (stable disease or better), time to response, duration of response, time to progression, progression-free survival, and overall survival. Results Objective responses were noted in 11 of 26 patients (overall response rate, 42%; 95% CI, 23% to 63%), including four complete responses and one unconfirmed complete response. The tumor control rate was 73%. The median time to response and duration of response were 1.9 months and not estimable, respectively, and the median time to progression was 3.8 months. The median progression-free survival and overall survival were 3.8 and 20.3 months, respectively. The most frequent grade ≥ 3 adverse events were neutropenia (65%), leukopenia (38%), lymphopenia (38%), and thrombocytopenia (23%), which were all manageable and reversible. Conclusion Lenalidomide demonstrated clinically meaningful antitumor activity and an acceptable toxicity profile in patients with relapsed or recurrent aggressive ATL, hinting at its potential to become a treatment option. Further investigations of lenalidomide in ATL and other mature T-cell neoplasms are warranted.
Takashi Ishida, Nagoya City University Graduate School of Medical Sciences, Aichi; Hiroshi Fujiwara, Ehime University Hospital, Ehime; Kisato Nosaka, Kumamoto University Hospital, Kumamoto; Naoya Taira, Heart Life Hospital, Okinawa; Yasunobu Abe, Kyushu Cancer Center, Fukuoka; Yoshitaka Imaizumi, Nagasaki University Hospital; Yukiyoshi Moriuchi, Sasebo City General Hospital; Tatsuro Jo, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki; Kenichi Ishizawa, Tohoku University Hospital, Miyagi; Kensei Tobinai, National Cancer Center Hospital; Shuichi Midorikawa, Wanda Ruiz, and Tomoko Ohtsu, Celgene K.K., Tokyo; Kunihiro Tsukasaki, National Cancer Center Hospital East, Chiba; Shigeki Ito, Iwate Medical University, Iwate; Makoto Yoshimitsu, Kagoshima University Hospital; Maki Otsuka, National Hospital Organization Kagoshima Medical Center, Kagoshima; and Michinori Ogura, Tokai Central Hospital, Gifu, Japan.
Takashi
T
Ishida
Takashi Ishida, Nagoya City University Graduate School of Medical Sciences, Aichi; Hiroshi Fujiwara, Ehime University Hospital, Ehime; Kisato Nosaka, Kumamoto University Hospital, Kumamoto; Naoya Taira, Heart Life Hospital, Okinawa; Yasunobu Abe, Kyushu Cancer Center, Fukuoka; Yoshitaka Imaizumi, Nagasaki University Hospital; Yukiyoshi Moriuchi, Sasebo City General Hospital; Tatsuro Jo, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki; Kenichi Ishizawa, Tohoku University Hospital, Miyagi; Kensei Tobinai, National Cancer Center Hospital; Shuichi Midorikawa, Wanda Ruiz, and Tomoko Ohtsu, Celgene K.K., Tokyo; Kunihiro Tsukasaki, National Cancer Center Hospital East, Chiba; Shigeki Ito, Iwate Medical University, Iwate; Makoto Yoshimitsu, Kagoshima University Hospital; Maki Otsuka, National Hospital Organization Kagoshima Medical Center, Kagoshima; and Michinori Ogura, Tokai Central Hospital, Gifu, Japan.
Hiroshi
H
Fujiwara
Takashi Ishida, Nagoya City University Graduate School of Medical Sciences, Aichi; Hiroshi Fujiwara, Ehime University Hospital, Ehime; Kisato Nosaka, Kumamoto University Hospital, Kumamoto; Naoya Taira, Heart Life Hospital, Okinawa; Yasunobu Abe, Kyushu Cancer Center, Fukuoka; Yoshitaka Imaizumi, Nagasaki University Hospital; Yukiyoshi Moriuchi, Sasebo City General Hospital; Tatsuro Jo, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki; Kenichi Ishizawa, Tohoku University Hospital, Miyagi; Kensei Tobinai, National Cancer Center Hospital; Shuichi Midorikawa, Wanda Ruiz, and Tomoko Ohtsu, Celgene K.K., Tokyo; Kunihiro Tsukasaki, National Cancer Center Hospital East, Chiba; Shigeki Ito, Iwate Medical University, Iwate; Makoto Yoshimitsu, Kagoshima University Hospital; Maki Otsuka, National Hospital Organization Kagoshima Medical Center, Kagoshima; and Michinori Ogura, Tokai Central Hospital, Gifu, Japan.
Kisato
K
Nosaka
Takashi Ishida, Nagoya City University Graduate School of Medical Sciences, Aichi; Hiroshi Fujiwara, Ehime University Hospital, Ehime; Kisato Nosaka, Kumamoto University Hospital, Kumamoto; Naoya Taira, Heart Life Hospital, Okinawa; Yasunobu Abe, Kyushu Cancer Center, Fukuoka; Yoshitaka Imaizumi, Nagasaki University Hospital; Yukiyoshi Moriuchi, Sasebo City General Hospital; Tatsuro Jo, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki; Kenichi Ishizawa, Tohoku University Hospital, Miyagi; Kensei Tobinai, National Cancer Center Hospital; Shuichi Midorikawa, Wanda Ruiz, and Tomoko Ohtsu, Celgene K.K., Tokyo; Kunihiro Tsukasaki, National Cancer Center Hospital East, Chiba; Shigeki Ito, Iwate Medical University, Iwate; Makoto Yoshimitsu, Kagoshima University Hospital; Maki Otsuka, National Hospital Organization Kagoshima Medical Center, Kagoshima; and Michinori Ogura, Tokai Central Hospital, Gifu, Japan.
Naoya
N
Taira
Takashi Ishida, Nagoya City University Graduate School of Medical Sciences, Aichi; Hiroshi Fujiwara, Ehime University Hospital, Ehime; Kisato Nosaka, Kumamoto University Hospital, Kumamoto; Naoya Taira, Heart Life Hospital, Okinawa; Yasunobu Abe, Kyushu Cancer Center, Fukuoka; Yoshitaka Imaizumi, Nagasaki University Hospital; Yukiyoshi Moriuchi, Sasebo City General Hospital; Tatsuro Jo, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki; Kenichi Ishizawa, Tohoku University Hospital, Miyagi; Kensei Tobinai, National Cancer Center Hospital; Shuichi Midorikawa, Wanda Ruiz, and Tomoko Ohtsu, Celgene K.K., Tokyo; Kunihiro Tsukasaki, National Cancer Center Hospital East, Chiba; Shigeki Ito, Iwate Medical University, Iwate; Makoto Yoshimitsu, Kagoshima University Hospital; Maki Otsuka, National Hospital Organization Kagoshima Medical Center, Kagoshima; and Michinori Ogura, Tokai Central Hospital, Gifu, Japan.
Yasunobu
Y
Abe
Takashi Ishida, Nagoya City University Graduate School of Medical Sciences, Aichi; Hiroshi Fujiwara, Ehime University Hospital, Ehime; Kisato Nosaka, Kumamoto University Hospital, Kumamoto; Naoya Taira, Heart Life Hospital, Okinawa; Yasunobu Abe, Kyushu Cancer Center, Fukuoka; Yoshitaka Imaizumi, Nagasaki University Hospital; Yukiyoshi Moriuchi, Sasebo City General Hospital; Tatsuro Jo, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki; Kenichi Ishizawa, Tohoku University Hospital, Miyagi; Kensei Tobinai, National Cancer Center Hospital; Shuichi Midorikawa, Wanda Ruiz, and Tomoko Ohtsu, Celgene K.K., Tokyo; Kunihiro Tsukasaki, National Cancer Center Hospital East, Chiba; Shigeki Ito, Iwate Medical University, Iwate; Makoto Yoshimitsu, Kagoshima University Hospital; Maki Otsuka, National Hospital Organization Kagoshima Medical Center, Kagoshima; and Michinori Ogura, Tokai Central Hospital, Gifu, Japan.
Yoshitaka
Y
Imaizumi
Takashi Ishida, Nagoya City University Graduate School of Medical Sciences, Aichi; Hiroshi Fujiwara, Ehime University Hospital, Ehime; Kisato Nosaka, Kumamoto University Hospital, Kumamoto; Naoya Taira, Heart Life Hospital, Okinawa; Yasunobu Abe, Kyushu Cancer Center, Fukuoka; Yoshitaka Imaizumi, Nagasaki University Hospital; Yukiyoshi Moriuchi, Sasebo City General Hospital; Tatsuro Jo, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki; Kenichi Ishizawa, Tohoku University Hospital, Miyagi; Kensei Tobinai, National Cancer Center Hospital; Shuichi Midorikawa, Wanda Ruiz, and Tomoko Ohtsu, Celgene K.K., Tokyo; Kunihiro Tsukasaki, National Cancer Center Hospital East, Chiba; Shigeki Ito, Iwate Medical University, Iwate; Makoto Yoshimitsu, Kagoshima University Hospital; Maki Otsuka, National Hospital Organization Kagoshima Medical Center, Kagoshima; and Michinori Ogura, Tokai Central Hospital, Gifu, Japan.
Yukiyoshi
Y
Moriuchi
Takashi Ishida, Nagoya City University Graduate School of Medical Sciences, Aichi; Hiroshi Fujiwara, Ehime University Hospital, Ehime; Kisato Nosaka, Kumamoto University Hospital, Kumamoto; Naoya Taira, Heart Life Hospital, Okinawa; Yasunobu Abe, Kyushu Cancer Center, Fukuoka; Yoshitaka Imaizumi, Nagasaki University Hospital; Yukiyoshi Moriuchi, Sasebo City General Hospital; Tatsuro Jo, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki; Kenichi Ishizawa, Tohoku University Hospital, Miyagi; Kensei Tobinai, National Cancer Center Hospital; Shuichi Midorikawa, Wanda Ruiz, and Tomoko Ohtsu, Celgene K.K., Tokyo; Kunihiro Tsukasaki, National Cancer Center Hospital East, Chiba; Shigeki Ito, Iwate Medical University, Iwate; Makoto Yoshimitsu, Kagoshima University Hospital; Maki Otsuka, National Hospital Organization Kagoshima Medical Center, Kagoshima; and Michinori Ogura, Tokai Central Hospital, Gifu, Japan.
Tatsuro
T
Jo
Takashi Ishida, Nagoya City University Graduate School of Medical Sciences, Aichi; Hiroshi Fujiwara, Ehime University Hospital, Ehime; Kisato Nosaka, Kumamoto University Hospital, Kumamoto; Naoya Taira, Heart Life Hospital, Okinawa; Yasunobu Abe, Kyushu Cancer Center, Fukuoka; Yoshitaka Imaizumi, Nagasaki University Hospital; Yukiyoshi Moriuchi, Sasebo City General Hospital; Tatsuro Jo, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki; Kenichi Ishizawa, Tohoku University Hospital, Miyagi; Kensei Tobinai, National Cancer Center Hospital; Shuichi Midorikawa, Wanda Ruiz, and Tomoko Ohtsu, Celgene K.K., Tokyo; Kunihiro Tsukasaki, National Cancer Center Hospital East, Chiba; Shigeki Ito, Iwate Medical University, Iwate; Makoto Yoshimitsu, Kagoshima University Hospital; Maki Otsuka, National Hospital Organization Kagoshima Medical Center, Kagoshima; and Michinori Ogura, Tokai Central Hospital, Gifu, Japan.
Kenichi
K
Ishizawa
Takashi Ishida, Nagoya City University Graduate School of Medical Sciences, Aichi; Hiroshi Fujiwara, Ehime University Hospital, Ehime; Kisato Nosaka, Kumamoto University Hospital, Kumamoto; Naoya Taira, Heart Life Hospital, Okinawa; Yasunobu Abe, Kyushu Cancer Center, Fukuoka; Yoshitaka Imaizumi, Nagasaki University Hospital; Yukiyoshi Moriuchi, Sasebo City General Hospital; Tatsuro Jo, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki; Kenichi Ishizawa, Tohoku University Hospital, Miyagi; Kensei Tobinai, National Cancer Center Hospital; Shuichi Midorikawa, Wanda Ruiz, and Tomoko Ohtsu, Celgene K.K., Tokyo; Kunihiro Tsukasaki, National Cancer Center Hospital East, Chiba; Shigeki Ito, Iwate Medical University, Iwate; Makoto Yoshimitsu, Kagoshima University Hospital; Maki Otsuka, National Hospital Organization Kagoshima Medical Center, Kagoshima; and Michinori Ogura, Tokai Central Hospital, Gifu, Japan.
Kensei
K
Tobinai
Takashi Ishida, Nagoya City University Graduate School of Medical Sciences, Aichi; Hiroshi Fujiwara, Ehime University Hospital, Ehime; Kisato Nosaka, Kumamoto University Hospital, Kumamoto; Naoya Taira, Heart Life Hospital, Okinawa; Yasunobu Abe, Kyushu Cancer Center, Fukuoka; Yoshitaka Imaizumi, Nagasaki University Hospital; Yukiyoshi Moriuchi, Sasebo City General Hospital; Tatsuro Jo, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki; Kenichi Ishizawa, Tohoku University Hospital, Miyagi; Kensei Tobinai, National Cancer Center Hospital; Shuichi Midorikawa, Wanda Ruiz, and Tomoko Ohtsu, Celgene K.K., Tokyo; Kunihiro Tsukasaki, National Cancer Center Hospital East, Chiba; Shigeki Ito, Iwate Medical University, Iwate; Makoto Yoshimitsu, Kagoshima University Hospital; Maki Otsuka, National Hospital Organization Kagoshima Medical Center, Kagoshima; and Michinori Ogura, Tokai Central Hospital, Gifu, Japan.
Kunihiro
K
Tsukasaki
Takashi Ishida, Nagoya City University Graduate School of Medical Sciences, Aichi; Hiroshi Fujiwara, Ehime University Hospital, Ehime; Kisato Nosaka, Kumamoto University Hospital, Kumamoto; Naoya Taira, Heart Life Hospital, Okinawa; Yasunobu Abe, Kyushu Cancer Center, Fukuoka; Yoshitaka Imaizumi, Nagasaki University Hospital; Yukiyoshi Moriuchi, Sasebo City General Hospital; Tatsuro Jo, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki; Kenichi Ishizawa, Tohoku University Hospital, Miyagi; Kensei Tobinai, National Cancer Center Hospital; Shuichi Midorikawa, Wanda Ruiz, and Tomoko Ohtsu, Celgene K.K., Tokyo; Kunihiro Tsukasaki, National Cancer Center Hospital East, Chiba; Shigeki Ito, Iwate Medical University, Iwate; Makoto Yoshimitsu, Kagoshima University Hospital; Maki Otsuka, National Hospital Organization Kagoshima Medical Center, Kagoshima; and Michinori Ogura, Tokai Central Hospital, Gifu, Japan.
Shigeki
S
Ito
Takashi Ishida, Nagoya City University Graduate School of Medical Sciences, Aichi; Hiroshi Fujiwara, Ehime University Hospital, Ehime; Kisato Nosaka, Kumamoto University Hospital, Kumamoto; Naoya Taira, Heart Life Hospital, Okinawa; Yasunobu Abe, Kyushu Cancer Center, Fukuoka; Yoshitaka Imaizumi, Nagasaki University Hospital; Yukiyoshi Moriuchi, Sasebo City General Hospital; Tatsuro Jo, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki; Kenichi Ishizawa, Tohoku University Hospital, Miyagi; Kensei Tobinai, National Cancer Center Hospital; Shuichi Midorikawa, Wanda Ruiz, and Tomoko Ohtsu, Celgene K.K., Tokyo; Kunihiro Tsukasaki, National Cancer Center Hospital East, Chiba; Shigeki Ito, Iwate Medical University, Iwate; Makoto Yoshimitsu, Kagoshima University Hospital; Maki Otsuka, National Hospital Organization Kagoshima Medical Center, Kagoshima; and Michinori Ogura, Tokai Central Hospital, Gifu, Japan.
Makoto
M
Yoshimitsu
Takashi Ishida, Nagoya City University Graduate School of Medical Sciences, Aichi; Hiroshi Fujiwara, Ehime University Hospital, Ehime; Kisato Nosaka, Kumamoto University Hospital, Kumamoto; Naoya Taira, Heart Life Hospital, Okinawa; Yasunobu Abe, Kyushu Cancer Center, Fukuoka; Yoshitaka Imaizumi, Nagasaki University Hospital; Yukiyoshi Moriuchi, Sasebo City General Hospital; Tatsuro Jo, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki; Kenichi Ishizawa, Tohoku University Hospital, Miyagi; Kensei Tobinai, National Cancer Center Hospital; Shuichi Midorikawa, Wanda Ruiz, and Tomoko Ohtsu, Celgene K.K., Tokyo; Kunihiro Tsukasaki, National Cancer Center Hospital East, Chiba; Shigeki Ito, Iwate Medical University, Iwate; Makoto Yoshimitsu, Kagoshima University Hospital; Maki Otsuka, National Hospital Organization Kagoshima Medical Center, Kagoshima; and Michinori Ogura, Tokai Central Hospital, Gifu, Japan.
Maki
M
Otsuka
Takashi Ishida, Nagoya City University Graduate School of Medical Sciences, Aichi; Hiroshi Fujiwara, Ehime University Hospital, Ehime; Kisato Nosaka, Kumamoto University Hospital, Kumamoto; Naoya Taira, Heart Life Hospital, Okinawa; Yasunobu Abe, Kyushu Cancer Center, Fukuoka; Yoshitaka Imaizumi, Nagasaki University Hospital; Yukiyoshi Moriuchi, Sasebo City General Hospital; Tatsuro Jo, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki; Kenichi Ishizawa, Tohoku University Hospital, Miyagi; Kensei Tobinai, National Cancer Center Hospital; Shuichi Midorikawa, Wanda Ruiz, and Tomoko Ohtsu, Celgene K.K., Tokyo; Kunihiro Tsukasaki, National Cancer Center Hospital East, Chiba; Shigeki Ito, Iwate Medical University, Iwate; Makoto Yoshimitsu, Kagoshima University Hospital; Maki Otsuka, National Hospital Organization Kagoshima Medical Center, Kagoshima; and Michinori Ogura, Tokai Central Hospital, Gifu, Japan.
Michinori
M
Ogura
Takashi Ishida, Nagoya City University Graduate School of Medical Sciences, Aichi; Hiroshi Fujiwara, Ehime University Hospital, Ehime; Kisato Nosaka, Kumamoto University Hospital, Kumamoto; Naoya Taira, Heart Life Hospital, Okinawa; Yasunobu Abe, Kyushu Cancer Center, Fukuoka; Yoshitaka Imaizumi, Nagasaki University Hospital; Yukiyoshi Moriuchi, Sasebo City General Hospital; Tatsuro Jo, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki; Kenichi Ishizawa, Tohoku University Hospital, Miyagi; Kensei Tobinai, National Cancer Center Hospital; Shuichi Midorikawa, Wanda Ruiz, and Tomoko Ohtsu, Celgene K.K., Tokyo; Kunihiro Tsukasaki, National Cancer Center Hospital East, Chiba; Shigeki Ito, Iwate Medical University, Iwate; Makoto Yoshimitsu, Kagoshima University Hospital; Maki Otsuka, National Hospital Organization Kagoshima Medical Center, Kagoshima; and Michinori Ogura, Tokai Central Hospital, Gifu, Japan.
Shuichi
S
Midorikawa
Takashi Ishida, Nagoya City University Graduate School of Medical Sciences, Aichi; Hiroshi Fujiwara, Ehime University Hospital, Ehime; Kisato Nosaka, Kumamoto University Hospital, Kumamoto; Naoya Taira, Heart Life Hospital, Okinawa; Yasunobu Abe, Kyushu Cancer Center, Fukuoka; Yoshitaka Imaizumi, Nagasaki University Hospital; Yukiyoshi Moriuchi, Sasebo City General Hospital; Tatsuro Jo, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki; Kenichi Ishizawa, Tohoku University Hospital, Miyagi; Kensei Tobinai, National Cancer Center Hospital; Shuichi Midorikawa, Wanda Ruiz, and Tomoko Ohtsu, Celgene K.K., Tokyo; Kunihiro Tsukasaki, National Cancer Center Hospital East, Chiba; Shigeki Ito, Iwate Medical University, Iwate; Makoto Yoshimitsu, Kagoshima University Hospital; Maki Otsuka, National Hospital Organization Kagoshima Medical Center, Kagoshima; and Michinori Ogura, Tokai Central Hospital, Gifu, Japan.
Wanda
W
Ruiz
Takashi Ishida, Nagoya City University Graduate School of Medical Sciences, Aichi; Hiroshi Fujiwara, Ehime University Hospital, Ehime; Kisato Nosaka, Kumamoto University Hospital, Kumamoto; Naoya Taira, Heart Life Hospital, Okinawa; Yasunobu Abe, Kyushu Cancer Center, Fukuoka; Yoshitaka Imaizumi, Nagasaki University Hospital; Yukiyoshi Moriuchi, Sasebo City General Hospital; Tatsuro Jo, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki; Kenichi Ishizawa, Tohoku University Hospital, Miyagi; Kensei Tobinai, National Cancer Center Hospital; Shuichi Midorikawa, Wanda Ruiz, and Tomoko Ohtsu, Celgene K.K., Tokyo; Kunihiro Tsukasaki, National Cancer Center Hospital East, Chiba; Shigeki Ito, Iwate Medical University, Iwate; Makoto Yoshimitsu, Kagoshima University Hospital; Maki Otsuka, National Hospital Organization Kagoshima Medical Center, Kagoshima; and Michinori Ogura, Tokai Central Hospital, Gifu, Japan.
Tomoko
T
Ohtsu
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D013792:Thalidomide; D000077269:Lenalidomide