A phase 2 trial of CHOP with anti-CCR4 antibody mogamulizumab for older patients with adult T-cell leukemia/lymphoma Available to Purchase

Author(s): Yoshimitsu, Makoto1; Choi, Ilseung2; Kusumoto, Shigeru3,4; Shimokawa, Mototsugu5; Utsunomiya, Atae6; Suehiro, Youko2; Hidaka, Tomonori7; Nosaka, Kisato8; Sasaki, Hidenori9; Rai, Shinya10; Tamura, Shinobu11; Owatari, Satsuki12; Koh, Ki-Ryang13; Nakamura, Daisuke1; Tokunaga, Masahito6; Sekine, Masaaki7; Sakamoto, Yuma14; Inagaki, Hiroshi14; Ishida, Takashi15; Ishitsuka, Kenji1;
Source: Blood (2025) 146 (12): 1440–1449.
Original Article
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The phase 2 trial of Moga-CHOP (CHOP + mogamulizumab) in older patients with aggressive adult T-cell leukemia/lymphoma (ATL) demonstrated a significant improvement in 1-year PFS (36.2% vs 16% historical control), with a 1-year OS of 66.0% and a CR rate of 64.6%. The overall response rate (ORR) was high at 91.7%, and the median overall survival (OS) reached 1.6 years. Notably, CCR4 mutations and Moga-associated cutaneous AEs correlated with better OS, and the regimen was generally tolerable with no unexpected toxicities. Bottom line: Moga-CHOP is now a strong first-line option for older, transplant-ineligible ATL patients, and it’s encouraging to see these survival gains in a population with historically poor outcomes.

ABSTRACT

No standard of care for older patients with aggressive adult T-cell leukemia/lymphoma (ATL) has been established. We evaluated the efficacy of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) every 2 weeks with mogamulizumab (Moga; Moga-CHOP-14) for older patients with untreated ATL. In this multicenter phase 2 trial, patients aged ≥66 years and those aged 56 to 65 years ineligible for transplantation received 6 cycles of Moga-CHOP-14, followed by 2 cycles of Moga monotherapy. The primary end point was 1-year progression-free survival (PFS). Secondary end points were the complete response (CR) rate, overall response rate (ORR), overall survival (OS), 1-year event-free survival (EFS), and safety. We also investigated the impact of CC chemokine receptor 4 (CCR4) mutation and Moga-associated cutaneous adverse events (cAEs) on PFS and OS. The study protocol was amended to allow the dosing interval to be extended to 21 days at the physician’s discretion. Among 48 evaluable patients, the 1-year PFS was 36.2% (90% confidence interval, 24.9-47.6), with a median follow-up of 1.6 years. The 1-year OS and EFS were 66.0% and 29.9%, respectively. CR and ORR were 64.6% and 91.7%. No unexpected toxicities were observed. Of 47 patients who received ≥2 cycles of CHOP, 20 (42.6%) received CHOP-14, among whom 12 (25.5%) completed 6 cycles. CCR4 mutation and Moga-associated cAEs were associated with better OS. This study showed that Moga-CHOP significantly improved PFS, although the optimal interval for CHOP remains undetermined. Moga-CHOP is now considered a preferable first-line treatment for this patient population. This trial was registered at https://jrct.mhlw.go.jp/en-top as #jRCTs041180130.

Author Affiliations

1Department of Hematology and Rheumatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan; 2Department of Hematology and Cell Therapy, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 3Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 4Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan; 5Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan; 6Department of Hematology, Imamura General Hospital, Kagoshima, Japan; 7Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan; 8Department of Hematology, Kumamoto University Hospital, Kumamoto, Japan; 9Division of Medical Oncology, Hematology, and Infectious Diseases, Faculty of Medicine, Fukuoka University, Fukuoka, Japan; 10Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka, Japan; 11Department of Hematology/Oncology, Wakayama Medical University, Wakayama, Japan; 12Department of Hematology, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan; 13Department of Hematology, Osaka General Hospital of West Japan Railway Company, Osaka, Japan; 14Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 15Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

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