N A Trum1,2, J Zain3, X U Martinez1, V Parekh4, M Afkhami4, F Abdulla1, K R Carson5, S T Rosen3,6, C L Bennett6,7,8, C Querfeld1,4,6. 1. Division of Dermatology, City of Hope Comprehensive Cancer Care Center, 1500 E Duarte Rd, Duarte, CA, 91010, USA. 2. Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, 69978, Israel. 3. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Care Center, 1500 E Duarte Rd, Duarte, CA, 91010, USA. 4. Department of Pathology, City of Hope Comprehensive Cancer Care Center, 1500 E Duarte Rd, Duarte, CA, 91010, USA. 5. Division of Hematology, Oncology, and Stem Cell Transplant, Rush University, 600 S. Paulina St, Chicago, IL, 60612, USA. 6. Beckman Research Institute, City of Hope Comprehensive Cancer Care Center, 1500 E Duarte Rd, Duarte, CA, 91010, USA. 7. Department of Comparative Medicine and Evidence Based Medicine, City of Hope Comprehensive Cancer Care Center, 1500 E Duarte Rd, Duarte, CA, 91010, USA. 8. College of Pharmacy, University of South Carolina, Columbia, SC, USA.
Abstract
BACKGROUND: Mogamulizumab is a humanized antibody against chemokine receptor type 4. It was recently approved by the US Food and Drug Administration for relapsed or refractory mycosis fungoides (MF) and Sézary syndrome (SS). The most commonly reported adverse event in the phase III licensing trial was drug eruption (28%), now termed mogamulizumab-associated rash (MAR). Clinical recommendations about MAR and its treatment differ between the current package insert and postapproval insights reported from two single-centre studies that focused on its characterization, but less so on outcomes and clinicopathological differentiation from cutaneous T-cell lymphoma (CTCL). OBJECTIVES: To describe our experience in the diagnosis of MAR and treatment of patients with CTCL with mogamulizumab. METHODS: This is a single-centre retrospective case series study. RESULTS: We found a higher incidence of MAR in patients with CTCL (17 of 24, 68%) than previously reported. MAR development is associated with complete (11 of 17) or partial (four of 17) responses, with an overall response rate of 88%, compared with 29% (two of seven) in patients without MAR. Diagnosis of MAR may be obscured by its ability to mimic key CTCL features both clinically and histologically, but an absence of T-cell-receptor clonality and relatively decreased CD4 : CD8 ratio compared with baseline lesions strongly favour MAR over recurrent disease. CONCLUSIONS: MAR has the potential to create a significant management problem for patients on mogamulizumab. Misidentification of MAR as recurrent CTCL may detrimentally result in the premature discontinuation of mogamulizumab in patients whose disease is historically hard to treat. Thorough clinicopathological investigation of new lesions during treatment with mogamulizumab is required to inform ideal treatment decisions and achieve better outcomes.
BACKGROUND: Mogamulizumab is a humanized antibody against chemokine receptor type 4. It was recently approved by the US Food and Drug Administration for relapsed or refractory mycosis fungoides (MF) and Sézary syndrome (SS). The most commonly reported adverse event in the phase III licensing trial was drug eruption (28%), now termed mogamulizumab-associated rash (MAR). Clinical recommendations about MAR and its treatment differ between the current package insert and postapproval insights reported from two single-centre studies that focused on its characterization, but less so on outcomes and clinicopathological differentiation from cutaneous T-cell lymphoma (CTCL). OBJECTIVES: To describe our experience in the diagnosis of MAR and treatment of patients with CTCL with mogamulizumab. METHODS: This is a single-centre retrospective case series study. RESULTS: We found a higher incidence of MAR in patients with CTCL (17 of 24, 68%) than previously reported. MAR development is associated with complete (11 of 17) or partial (four of 17) responses, with an overall response rate of 88%, compared with 29% (two of seven) in patients without MAR. Diagnosis of MAR may be obscured by its ability to mimic key CTCL features both clinically and histologically, but an absence of T-cell-receptor clonality and relatively decreased CD4 : CD8 ratio compared with baseline lesions strongly favour MAR over recurrent disease. CONCLUSIONS: MAR has the potential to create a significant management problem for patients on mogamulizumab. Misidentification of MAR as recurrent CTCL may detrimentally result in the premature discontinuation of mogamulizumab in patients whose disease is historically hard to treat. Thorough clinicopathological investigation of new lesions during treatment with mogamulizumab is required to inform ideal treatment decisions and achieve better outcomes.
Authors: Maria Estela Martinez-Escala; Alba L Posligua; Heather Wickless; Audrey Rutherford; Kimberly A Sable; Belen Rubio-Gonzalez; Xiaolong A Zhou; Jason B Kaplan; Barbara Pro; Jaehyuk Choi; Christiane Querfeld; Steven T Rosen; Joan Guitart Journal: J Am Acad Dermatol Date: 2018-01-04 Impact factor: 11.527
Authors: Y Masuda; K Tatsuno; S Kitano; H Miyazawa; J Ishibe; M Aoshima; T Shimauchi; T Fujiyama; T Ito; Y Tokura Journal: J Eur Acad Dermatol Venereol Date: 2018-01-31 Impact factor: 6.166
Authors: Maria L Espinosa; Morgan T Nguyen; Amaia Saenz Aguirre; Maria Estela Martinez-Escala; Jane Kim; Christina J Walker; David S Pontes; Jonathan I Silverberg; Jaehyuk Choi; Barbara Pro; Laura B Pincus; Joan Guitart; Xiaolong A Zhou Journal: J Am Acad Dermatol Date: 2020-03-27 Impact factor: 11.527
Authors: Jennifer Y Wang; Kelsey E Hirotsu; Tatiana M Neal; Shyam S Raghavan; Bernice Y Kwong; Michael S Khodadoust; Ryanne A Brown; Roberto A Novoa; Youn H Kim; Kerri E Rieger Journal: Am J Surg Pathol Date: 2020-12 Impact factor: 6.394
Authors: Youn H Kim; Martine Bagot; Lauren Pinter-Brown; Alain H Rook; Pierluigi Porcu; Steven M Horwitz; Sean Whittaker; Yoshiki Tokura; Maarten Vermeer; Pier Luigi Zinzani; Lubomir Sokol; Stephen Morris; Ellen J Kim; Pablo L Ortiz-Romero; Herbert Eradat; Julia Scarisbrick; Athanasios Tsianakas; Craig Elmets; Stephane Dalle; David C Fisher; Ahmad Halwani; Brian Poligone; John Greer; Maria Teresa Fierro; Amit Khot; Alison J Moskowitz; Amy Musiek; Andrei Shustov; Barbara Pro; Larisa J Geskin; Karen Dwyer; Junji Moriya; Mollie Leoni; Jeffrey S Humphrey; Stacie Hudgens; Dmitri O Grebennik; Kensei Tobinai; Madeleine Duvic Journal: Lancet Oncol Date: 2018-08-09 Impact factor: 41.316