TY - JOUR
T1 - Quality of Life Effect of the Anti-CCR4 Monoclonal Antibody Mogamulizumab Versus Vorinostat in Patients With Cutaneous T-cell Lymphoma
AU - Porcu, Pierluigi
AU - Hudgens, Stacie
AU - Horwitz, Steven
AU - Quaglino, Pietro
AU - Cowan, Richard
AU - Geskin, Larisa
AU - Beylot-Barry, Marie
AU - Floden, Lysbeth
AU - Bagot, Martine
AU - Tsianakas, Athanasios
AU - Moskowitz, Alison
AU - Huen, Auris
AU - Dreno, Brigitte
AU - Dalle, Stéphane
AU - Caballero, Dolores
AU - Leoni, Mollie
AU - Dale, Stephen
AU - Herr, Fiona
AU - Duvic, Madeleine
N1 - Funding Information:
The present study was funded in part through the National Institutes of Health National Cancer Institute Cancer Center Support (grant P30 CA008748 ). Medical writing assistance was provided by Chad Green, PharmD, MBA, of Clinical Outcomes Solutions. Additional editorial assistance was provided by MedVal Scientific Information Services, LLC (Princeton, NJ). Writing and editorial support was funded by Kyowa Kirin, Inc (Bedminster, NJ). Kyowa Kirin Pharmaceutical Development (Princeton, NJ), consulted with advisors and study investigators on the design of the study, provided financial and material support for the study, and, with the assistance of the study investigators, monitored the conduct of the study, collected data from the investigative centers, and analyzed the data. On behalf of all, we thank the patients and investigators who participated in the MAVORIC study.
Funding Information:
P.P. served in a consulting/advisory role with Celgene and Innate Pharma and received research funding from Celgene , Infinity , Millennium , OncoMed , and Seattle Genetics . S. Hudgens and L.F. are employees of Clinical Outcomes Solutions. S. Horwitz served in a consulting/advisory role with Affimed, Astex, Celgene, Kyowa Hakko Kirin, Millennium/Takeda, Trillium, and Verastem and received research funding from ADC Therapeutics , Aileron , Celgene , Corvus , Daiichi-Sankyo , Forty Seven , Millennium / Takeda , Portola , Seattle Genetics , Trillium , and Verastem . P.Q. served in a consulting/advisory role with 4SC, Actelion, Kyowa, Innate Pharma, Takeda, and Therakos. R.C. received honoraria from, served in a consulting/advisory role with, and provided expert testimony for, Kyowa Kirin . L.G. served in a consulting/advisory role with Actelion, Kyowa Kirin, Mallinkrodt, and Soligenix; received research funding from Helsinn , Kyowa Kirin , Merck , and Mallinkrodt ; and received personal fees for travel, accommodations, and expenses from Kyowa Kirin. M.B.-B. served in consulting/advisory role with, and received personal fees for travel, accommodations, and expenses from, Kyowa Kirin. M.B. holds stock or other ownership with Innate Pharma; served in a consulting/advisory role with Innate Pharma, Kyowa Kirin, and Takeda; and received personal fees for travel, accommodations, and expenses from Innate Pharma, Janssen, Kyowa Kirin, and Novartis. A.T. received honoraria from, served in a consulting/advisory role with, and received personal fees for travel, accommodations, and expenses from, Kyowa Kirin. A.M. served in a consulting/advisory role with ADC Therapeutics, Bristol-Myers Squibb, Cell Medica, Erytech, Kyowa Hakko Kirin, MiRagen, Seattle Genetics, and Takeda and received research funding from Bristol-Myers Squibb , Incyte , Merck , and Seattle Genetics . A.H served in a consulting/advisory role with Kyowa Kirin and Seattle Genetics; received research funding from Galderma , Kyowa Kirin , MiRagen , Rhizen , and Seattle Genetics ; and received personal fees for travel, accommodations, and expenses from Galderma. Stéphane Dalle received research funding from Kyowa Kirin . M.L., Stephen Dale, and F.H. are employees of Kyowa Kirin. M.D. served in a consulting/advisory role with Guide Point; served on a speakers’ bureau for Jonathan Woods; received research funding from Eisai , Kyowa Kiran , MiRagen , Seattle Genetics , and Trillium ; and received personal fees for travel, accommodations, and expenses from Soligenix. The remaining authors have stated that they have no conflicts of interest.
Funding Information:
P.P. served in a consulting/advisory role with Celgene and Innate Pharma and received research funding from Celgene, Infinity, Millennium, OncoMed, and Seattle Genetics. S. Hudgens and L.F. are employees of Clinical Outcomes Solutions. S. Horwitz served in a consulting/advisory role with Affimed, Astex, Celgene, Kyowa Hakko Kirin, Millennium/Takeda, Trillium, and Verastem and received research funding from ADC Therapeutics, Aileron, Celgene, Corvus, Daiichi-Sankyo, Forty Seven, Millennium/Takeda, Portola, Seattle Genetics, Trillium, and Verastem. P.Q. served in a consulting/advisory role with 4SC, Actelion, Kyowa, Innate Pharma, Takeda, and Therakos. R.C. received honoraria from, served in a consulting/advisory role with, and provided expert testimony for, Kyowa Kirin. L.G. served in a consulting/advisory role with Actelion, Kyowa Kirin, Mallinkrodt, and Soligenix; received research funding from Helsinn, Kyowa Kirin, Merck, and Mallinkrodt; and received personal fees for travel, accommodations, and expenses from Kyowa Kirin. M.B.-B. served in consulting/advisory role with, and received personal fees for travel, accommodations, and expenses from, Kyowa Kirin. M.B. holds stock or other ownership with Innate Pharma; served in a consulting/advisory role with Innate Pharma, Kyowa Kirin, and Takeda; and received personal fees for travel, accommodations, and expenses from Innate Pharma, Janssen, Kyowa Kirin, and Novartis. A.T. received honoraria from, served in a consulting/advisory role with, and received personal fees for travel, accommodations, and expenses from, Kyowa Kirin. A.M. served in a consulting/advisory role with ADC Therapeutics, Bristol-Myers Squibb, Cell Medica, Erytech, Kyowa Hakko Kirin, MiRagen, Seattle Genetics, and Takeda and received research funding from Bristol-Myers Squibb, Incyte, Merck, and Seattle Genetics. A.H served in a consulting/advisory role with Kyowa Kirin and Seattle Genetics; received research funding from Galderma, Kyowa Kirin, MiRagen, Rhizen, and Seattle Genetics; and received personal fees for travel, accommodations, and expenses from Galderma. St?phane Dalle received research funding from Kyowa Kirin. M.L., Stephen Dale, and F.H. are employees of Kyowa Kirin. M.D. served in a consulting/advisory role with Guide Point; served on a speakers? bureau for Jonathan Woods; received research funding from Eisai, Kyowa Kiran, MiRagen, Seattle Genetics, and Trillium; and received personal fees for travel, accommodations, and expenses from Soligenix. The remaining authors have stated that they have no conflicts of interest.The present study was funded in part through the National Institutes of Health National Cancer Institute Cancer Center Support (grant P30 CA008748). Medical writing assistance was provided by Chad Green, PharmD, MBA, of Clinical Outcomes Solutions. Additional editorial assistance was provided by MedVal Scientific Information Services, LLC (Princeton, NJ). Writing and editorial support was funded by Kyowa Kirin, Inc (Bedminster, NJ). Kyowa Kirin Pharmaceutical Development (Princeton, NJ), consulted with advisors and study investigators on the design of the study, provided financial and material support for the study, and, with the assistance of the study investigators, monitored the conduct of the study, collected data from the investigative centers, and analyzed the data. On behalf of all, we thank the patients and investigators who participated in the MAVORIC study.
Publisher Copyright:
© 2020 The Authors
PY - 2021/2
Y1 - 2021/2
N2 - Background: Sézary syndrome (SS) and mycosis fungoides (MF), 2 types of cutaneous T-cell lymphoma, cause significant morbidity and adversely affect patients’ quality of life (QoL). The present study assessed the QoL measurement changes in patients receiving mogamulizumab versus vorinostat. Patients and Methods: A multicenter phase III trial was conducted of patients with stage IB-IV MF/SS with ≥ 1 failed systemic therapy. The QoL measures included Skindex-29 and the Functional Assessment of Cancer Therapy–General. The symptoms, function, and QoL subdomains were longitudinally modeled using mixed models with prespecified covariates. Meaningful change thresholds (MCTs) were defined using distribution-based methods. The categorical changes by group over time and the time to clinically meaningful worsening were analyzed. Results: Of the 372 randomized patients, mogamulizumab demonstrated improvement in Skindex-29 symptoms (cycles 3, 5, and 7; P < .05) and functional (cycles 3 and 5; P < .05) scales. A significantly greater proportion of mogamulizumab-treated patients improved by MCTs or more from baseline in the Skindex-29 symptoms domain (cycles 3, 5, 7, and 11) and functioning domain (cycle 5). Significant differences in the Functional Assessment of Cancer Therapy–General physical well-being (cycles 1, 3, and 5; P < .05) were observed in favor of mogamulizumab and a greater proportion of patients had declined by MCTs or more at cycles 1, 3, 5, and 7 with vorinostat treatment. The median time to symptom worsening using Skindex-29 was 27.4 months for mogamulizumab versus 6.6 months for vorinostat. In the patients with SS, the time to worsening favored mogamulizumab (P < .005) for all Skindex-29 domains. The time to worsening was similar for the 2 MF treatment arms. Conclusion: The symptoms, function, and overall QoL of patients with MF/SS favored mogamulizumab over vorinostat across all time points. Patients with the greatest symptom burden and functional impairment derived the most QoL benefit from mogamulizumab. Cutaneous T-cell lymphoma, including mycosis fungoides and Sézary syndrome, cause itching and other symptoms that can impair patients’ quality of life (QoL). The present prespecified analysis examined in detail how monoclonal antibody mogamulizumab treatment improved patients’ symptoms, function, and overall QoL across time points relative to vorinostat, providing a health-related QoL benchmark for these patients.
AB - Background: Sézary syndrome (SS) and mycosis fungoides (MF), 2 types of cutaneous T-cell lymphoma, cause significant morbidity and adversely affect patients’ quality of life (QoL). The present study assessed the QoL measurement changes in patients receiving mogamulizumab versus vorinostat. Patients and Methods: A multicenter phase III trial was conducted of patients with stage IB-IV MF/SS with ≥ 1 failed systemic therapy. The QoL measures included Skindex-29 and the Functional Assessment of Cancer Therapy–General. The symptoms, function, and QoL subdomains were longitudinally modeled using mixed models with prespecified covariates. Meaningful change thresholds (MCTs) were defined using distribution-based methods. The categorical changes by group over time and the time to clinically meaningful worsening were analyzed. Results: Of the 372 randomized patients, mogamulizumab demonstrated improvement in Skindex-29 symptoms (cycles 3, 5, and 7; P < .05) and functional (cycles 3 and 5; P < .05) scales. A significantly greater proportion of mogamulizumab-treated patients improved by MCTs or more from baseline in the Skindex-29 symptoms domain (cycles 3, 5, 7, and 11) and functioning domain (cycle 5). Significant differences in the Functional Assessment of Cancer Therapy–General physical well-being (cycles 1, 3, and 5; P < .05) were observed in favor of mogamulizumab and a greater proportion of patients had declined by MCTs or more at cycles 1, 3, 5, and 7 with vorinostat treatment. The median time to symptom worsening using Skindex-29 was 27.4 months for mogamulizumab versus 6.6 months for vorinostat. In the patients with SS, the time to worsening favored mogamulizumab (P < .005) for all Skindex-29 domains. The time to worsening was similar for the 2 MF treatment arms. Conclusion: The symptoms, function, and overall QoL of patients with MF/SS favored mogamulizumab over vorinostat across all time points. Patients with the greatest symptom burden and functional impairment derived the most QoL benefit from mogamulizumab. Cutaneous T-cell lymphoma, including mycosis fungoides and Sézary syndrome, cause itching and other symptoms that can impair patients’ quality of life (QoL). The present prespecified analysis examined in detail how monoclonal antibody mogamulizumab treatment improved patients’ symptoms, function, and overall QoL across time points relative to vorinostat, providing a health-related QoL benchmark for these patients.
KW - FACT-G
KW - Mycosis fungoides
KW - Patient-reported outcome
KW - Skindex-29
KW - Sézary syndrome
UR - http://www.scopus.com/inward/record.url?scp=85096371983&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85096371983&partnerID=8YFLogxK
U2 - 10.1016/j.clml.2020.09.003
DO - 10.1016/j.clml.2020.09.003
M3 - Article
C2 - 33158772
AN - SCOPUS:85096371983
SN - 2152-2650
VL - 21
SP - 97
EP - 105
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 2
ER -