Mogamulizumab versus investigator’s choice of chemotherapy regimen in relapsed/refractory adult T-cell leukemia/lymphoma
Adrienne A. Phillips,
Paul A. Fields,
Olivier Hermine,
Juan C. Ramos,
Brady E. Beltran,
Juliana Pereira,
Farooq Wandroo,
Tatyana Feldman,
Graham P. Taylor,
Ahmed Sawas,
Jeffrey Humphrey,
Michael Kurman,
Junji Moriya,
Karen Dwyer,
Mollie Leoni,
Kevin Conlon,
Lucy Cook,
Jason Gonsky,
Steven M. Horwitz
Affiliations
Adrienne A. Phillips
Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA
Paul A. Fields
Department of Haematology Guy’s and St Thomas’ Hospitals NHS Trust Hospital, London, UK
Olivier Hermine
Department of Hematology, Necker University Hospital, Paris, France
Juan C. Ramos
Division of Hematology/Oncology, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, FL, USA
Brady E. Beltran
Hospital Nacional Edgardo Rebagliati Martins and Centro de Investigación de Medicina de Precision, Universidad de San Martin de Porres, Lima, Peru
Juliana Pereira
Department of Hematology, University of São Paulo, Brazil
Farooq Wandroo
Sandwell and West Birmingham Hospitals NHS Trust, West Bromwich, and University of Birmingham, UK
Tatyana Feldman
John Theurer Cancer Center, Hackensack UMC, NJ, USA
Graham P. Taylor
National Centre for Human Retrovirology, St Mary’s Hospital, Imperial College Healthcare NHS Trust, London, UK
Ahmed Sawas
Center for Lymphoid Malignancies, Columbia University Irving Medical Center, New York, NY, USA
Jeffrey Humphrey
Kyowa Kirin, Princeton, NJ, USA
Michael Kurman
Kyowa Kirin, Princeton, NJ, USA
Junji Moriya
Kyowa Kirin, Princeton, NJ, USA
Karen Dwyer
Kyowa Kirin, Princeton, NJ, USA
Mollie Leoni
Kyowa Kirin, Princeton, NJ, USA
Kevin Conlon
Warren Grant Magnuson Clinical Center, National Cancer Institute, Bethesda, MD, USA
Lucy Cook
Department of Haematology and National Centre for Human Retrovirology, Imperial College Healthcare NHS Trust, London, UK
Jason Gonsky
Division of Hematology/Oncology, Department of Medicine, New York City Health + Hospitals/Kings County and SUNY Downstate Medical Center, Brooklyn, NY, USA
Steven M. Horwitz
Hematology/Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Mogamulizumab, a humanized defucosylated anti-C-C chemokine receptor 4 monoclonal antibody, has been approved in Japan for the treatment of C-C chemokine receptor 4-positive adult T-cell leukemia/lymphoma (ATL). This phase II study evaluated efficacy and safety of mogamulizumab in ATL patients with acute, lymphoma, and chronic subtypes with relapsed/refractory, aggressive disease in the US, Europe, and Latin America. With stratification by subtype, patients were randomized 2:1 to intravenous mogamulizumab 1.0 mg/kg once weekly for 4 weeks and biweekly thereafter (n=47) or investigator’s choice of chemotherapy (n=24). The primary end point was confirmed overall response rate (cORR) confirmed on a subsequent assessment at 8 weeks by blinded independent review. ORR was 11% (95%CI: 4-23%) and 0% (95%CI: 0-14%) in the mogamulizumab and chemotherapy arms, respectively. Best response was 28% and 8% in the respective arms. The observed hazard ratio for progression-free survival was 0.71 (95%CI: 0.41-1.21) and, after post hoc adjustment for performance status imbalance, 0.57 (95%CI: 0.337-0.983). The most frequent treatment-related adverse (grade ≥3) events with mogamulizumab were infusion-related reaction and thrombocytopenia (each 9%). Relapsed/refractory ATL is an aggressive, poor prognosis disease with a high unmet need. Investigator’s choice chemotherapy did not result in tumor response in this trial; however, mogamulizumab treatment resulted in 11% cORR, with a tolerable safety profile.
