Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study.
This multicentre, randomized, phase II study was conducted to examine whether the addition of mogamulizumab, a humanized anti-CC chemokine receptor 4 antibody, to mLSG15, a dose-intensified chemotherapy, further increases efficacy without compromising safety of patients with newly diagnosed aggressive adult T-cell leukaemia-lymphoma (ATL). Patients were assigned 1:1 to receive mLSG15 plus mogamulizumab or mLSG15 alone. The primary endpoint was the complete response rate (%CR); secondary endpoints included the overall response rate (ORR) and safety. The %CR and ORR in the mLSG15-plus-mogamulizumab arm (n = 29) were 52% [95% confidence interval (CI), 33-71%] and 86%, respectively; the corresponding values in the mLSG15 arm (n = 24) were 33% (95% CI, 16-55%) and 75%, respectively. Grade ≥ 3 treatment-emergent adverse events, including anaemia, thrombocytopenia, lymphopenia, leucopenia and decreased appetite, were observed more frequently (≥10% difference) in the mLSG15-plus-mogamulizumab arm. Several adverse events, including skin disorders, cytomegalovirus infection, pyrexia, hyperglycaemia and interstitial lung disease, were observed only in the mLSG15-plus-mogamulizumab arm. Although the combination strategy showed a potentially less favourable safety profile, a higher %CR was achieved, providing the basis for further investigation of this novel treatment for newly diagnosed aggressive ATL. This study was registered at ClinicalTrials.gov, identifier: NCT01173887.
Department of Haematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Takashi
T
Ishida
Department of Haematology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan.
Tatsuro
T
Jo
Department of Haematology and Institute for Clinical Research, National Hospital Organization Kumamoto Medical Centre, Kumamoto, Japan.
Shigeki
S
Takemoto
Department of Haematology, Kumamoto Shinto General Hospital, Kumamoto, Japan.
Hitoshi
H
Suzushima
Department of Haematology and Immunology, Kagoshima University Hospital, Kagoshima, Japan.
Kimiharu
K
Uozumi
Department of Haematology and Cell Therapy, Aichi Cancer Centre Hospital, Nagoya, Japan.
Kazuhito
K
Yamamoto
Department of Haematology, National Hospital Organization Kyushu Cancer Centre, Fukuoka, Japan.
Naokuni
N
Uike
Department of Haematology, Oita Prefectural Hospital, Oita, Japan.
Yoshio
Y
Saburi
Cancer Centre, Kumamoto University Hospital, Kumamoto, Japan.
Kisato
K
Nosaka
Department of Haematology, Imamura Bun-in Hospital, Kagoshima, Japan.
Atae
A
Utsunomiya
Department of Haematology, National Cancer Centre Hospital, Tokyo, Japan.
Kensei
K
Tobinai
Department of Bioregulatory Medicine, Ehime University Graduate School of Medicine, Toon, Japan.
Hiroshi
H
Fujiwara
Division of Medical Oncology, Haematology, and Infectious Diseases, Department of Internal Medicine, Fukuoka University, Fukuoka, Japan.
Kenji
K
Ishitsuka
Department of Haematology, National Hospital Organization Nagasaki Medical Centre, Ohmura, Japan.
Shinichiro
S
Yoshida
Department of Internal Medicine, Heartlife Hospital, Okinawa, Japan.
Naoya
N
Taira
Department of Haematology, Sasebo City General Hospital, Sasebo, Japan.
Yukiyoshi
Y
Moriuchi
Department of Haematology, Kokura Memorial Hospital, Kitakyushu, Japan.
Kazunori
K
Imada
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Toshihiro
T
Miyamoto
Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.
Shiro
S
Akinaga
Department of Haematology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan.
Masao
M
Tomonaga
Department of Tumour Immunology, Aichi Medical University School of Medicine, Nagoya, Japan.
Ryuzo
R
Ueda
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D018450:Disease Progression; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009607:Nitrosourea Compounds / Q000009:adverse effects / Q000627:therapeutic use; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use; D014751:Vindesine / Q000009:adverse effects / Q000627:therapeutic use
D061067:Antibodies, Monoclonal, Humanized; D009607:Nitrosourea Compounds; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D016190:Carboplatin; D014751:Vindesine; C549035:mogamulizumab
CCR4; adult T-cell leukaemia-lymphoma; antibody therapy; mogamulizumab; randomized phase II study