Patient-reported quality of life in patients with relapsed/refractory cutaneous T-cell lymphoma: Results from the randomised phase III ALCANZA study

Abstract

Background: Brentuximab vedotin was approved for adult patients with CD30-expressing cutaneous T-cell lymphoma treated with prior systemic therapy based on improved response rates and progression-free survival with brentuximab vedotin (1.8 mg/kg once every 3 weeks; ≤16 cycles) versus physician's choice (methotrexate/bexarotene; ≤48 weeks) in the phase III ALCANZA study. Quality of life (QoL) in ALCANZA patients was also examined.

Methods: QoL measures in ALCANZA were based on the Skindex-29, Functional Assessment of Cancer Therapy-General (FACT-G) and European QoL 5-dimension (EQ-5D) questionnaires.

Results: Mean maximum reduction from the baseline Skindex-29 symptom domain score (key secondary end-point) was greater with brentuximab vedotin than physician's choice (-27.96 versus -8.62); the difference, -18.9 (95% confidence interval -26.6, -11.2; adjusted p < 0.001), exceeded the study-defined minimally important difference (9.0-12.3). Mean changes from baseline to end-of-treatment visit total FACT-G scores were similar with brentuximab vedotin and physician's choice (0.15 versus -2.29). EQ-5D changes were also comparable between arms. Among brentuximab vedotin-treated patients with peripheral neuropathy (PN), mean maximum reduction in Skindex-29 symptom domain was -35.54 versus -11.11 in patients without PN. PN had no meaningful effect on FACT-G and EQ-5D QoL scores.

Conclusions: In summary, brentuximab vedotin produced superior reductions in symptom burden compared with physician's choice, without adversely impacting QoL. QoL was unaffected by the presence of PN in brentuximab vedotin-treated patients.

Clinical trial registration: NCT01578499.

Keywords: Brentuximab vedotin; CD30; Clinical trial; Cutaneous T-cell lymphoma; Phase III; Quality of life.

Conflict of interest statement

Conflict of interest statement S.W., P.W., J.A.S. and L.G. declare no conflicts of interest. R.D. reports intermittent, project-focused consulting and/or advisory relationships with Novartis, MSD, Bristol-Myers Squibb, Roche, Amgen, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Pierre Fabre, Sun Pharma and Sanofi. H.M.P. reports consultancy, advisory roles or honoraria from Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Celgene and Eisai, and research funding from Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. S.M.H. reports consultancy or advisory roles from Affimed, Aileron Therapeutics, Merck Sharp and Dome, Kyowa Hakko Kirin Pharma, Corvus Pharmaceuticals, Inc., Celgene, Portola Pharmaceuticals, Takeda Millennium, Innate Pharma, Verastem, Miragen Therapeutics, Inc. and Seattle Genetics, and research funding from ADCT Therapeutics, Aileron, Forty-Seven, Infinity/Verastem, Kyowa Hakko Kirin Pharma, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Seattle Genetics, Inc., Celgene and Trillium. M.D. reports research funding and consultancy from Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, and Seattle Genetics, Inc. J.S. reports consultancy or advisory roles from Helsinn, Kyowa Hakko Kirin, Millennium Pharmaceuticals, Inc., Innate Pharma, 4SC and Mallinckrodt. P.Q. reports advisory roles from 4SC, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Therakos, Innate Pharma and Kyowa Hakko Kirin. P.L.Z. reports consultancy, advisory and/or speakers bureau roles from Verastem, Celltrion, Gilead, Janssen-Cilag, Bristol-Myers Squibb, Servier, Sandoz, Merck Sharp & Dhome, Immune Design, Celgene, Portola, Roche, EUSA Pharma, Kyowa Hakko Kirin and Sanofi. H.E. reports consultancy or advisory roles from Genentech, Roche, AbbVie and Pharmacyclics, honoraria from Genentech, Roche, AbbVie, Pharmacyclics and Millennium Pharmaceuticals, Inc., and research funding from Genentech, Roche, AbbVie, Pharmacyclics, ATARA and Celgene. L.P.B. reports consultancy fees and honoraria from Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. P.L.O.R. reports travel support from Janssen and Almirall, research support from MEDA, advisory roles from Takeda, Kyowa Hakko Kirin, Actelion, 4SC, Innate Pharma and MiRagen, and a patent on the clinical use of PLCG1 mutation detection. O.E.A. reports consultancy or advisory roles from Trillium Therapeutics and Bioniz, and research funding from Trillium Therapeutics and Pfizer. A.H. reports advisory board participation from Precision Oncology. J.W. reports an advisory role for Roche, Celgene, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Janssen-Cilag, Servier, Amgen, Bristol-Myers Squibb, Incyte and Abbvie, research funding from Roche, GSK/Novartis, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited and Janssen-Cilag, honoraria from Roche, Celgene, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Janssen-Cilag and Servier, and conference travel support from Roche. Y.W., J.L., A.R. and J.F. report employment and stock ownership from Seattle Genetics, Inc. Y.Z., V.B., M.L., E.Z. and M.R.D. report employment from Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Y.H.K. reports honoraria from Eisai, Kyowa Hakko Kirin, Millennium Pharmaceuticals, Inc., Seattle Genetics, Inc., Medivir, Innate Pharma, Portola and Corvus, and research funding from Eisai, Kyowa Hakko Kirin, Merck Sharp & Dhome, Horizon, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Seattle Genetics, Inc., Soligenix, MiRagen, Forty-Seven, Neumedicine, Innate Pharma, Portola, Trillium, Galderma and Elorac.

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