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

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10 Scopus citations

Abstract

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. Trial registered at clinicaltrials.gov identifier: 01626664.

Original languageEnglish (US)
Pages (from-to)993-1003
Number of pages11
JournalHaematologica
Volume104
Issue number5
DOIs
StatePublished - Apr 30 2019

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ASJC Scopus subject areas

  • Hematology

Cite this

Phillips, A. A., Fields, P. A., Hermine, O., Ramos, J. C., Beltran, B. E., Pereira, J., Wandroo, F., Feldman, T., Taylor, G. P., Sawas, A., Humphrey, J., Kurman, M., Moriya, J., Dwyer, K., Leoni, M., Conlon, K., Cook, L., Gonsky, J., & Horwitz, S. M. (2019). Mogamulizumab versus investigator’s choice of chemotherapy regimen in relapsed/ refractory adult T-cell leukemia/lymphoma. Haematologica, 104(5), 993-1003. https://doi.org/10.3324/haematol.2018.205096