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Multiple Myeloma, Gammopathies

Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: a multicenter IMWG study

Abstract

Introduction of new myeloma therapies offers new options for patients refractory to immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). In this multicenter study, patients with relapsed multiple myeloma, who have received at least three prior lines of therapy, are refractory to both an IMiD (lenalidomide or pomalidomide) and a PI (bortezomib or carfilzomib), and have been exposed to an alkylating agent were identified. The time patients met the above criteria was defined as time zero (T0). Five hundred and forty-three patients diagnosed between 2006 and 2014 were enrolled in this study. Median age at T0 was 62 years (range 31–87); 61% were males. The median duration between diagnosis and T0 was 3.1 years. The median number of lines of therapy before T0 was 4 (range 3–13). The median overall survival (OS) from T0 for the entire cohort was 13 (95% confidence interval (CI) 11, 15) months. At least one regimen recorded after T0 in 462 (85%) patients, with a median (95% CI) progression-free survival and OS from T0 of 5 (4, 6), and 15.2 (13, 17) months, respectively. The study provides the expected outcome of relapsed multiple myeloma that is refractory to a PI and an IMiD, a benchmark for comparison of new therapies being evaluated.

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Acknowledgements

Janssen Pharmaceuticals provided funding for the study.

Author contributions

All authors (except BGMD) provided patient data and were involved in manuscript preparation. SKK was involved in the statistical analysis.

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Correspondence to S K Kumar.

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Competing interests

SKK: research funding (Abbvie, Celgene, Janssen, Merck, Novartis, Roche, Sanofi and Takeda) and honoraria (Skyline Diagnostics); MAD: honoraria (Celgene, Janssen, Amgen and Takeda); ET: research funding and honoraria (Amgen, Celgene and Janssen), and honoraria (Novartis, GSK, Bristol Myers Squibb and Takeda); HG: research funding, advisory board and honoraria (Janssen, Celgene, Novartis and BMS), research funding and honoraria (Chugai), and advisory boards (Amgen and Takeda); JH: consultancy, honoraria and advisory board (Amgen), honoraria and advisory board (Janssen, Celgene and Novartis), honoraria (Bristol Myers Squibb) and research funding (Sanofi); MB: speakers bureau and advisory board (Celgene, Janssen-Cilag, Amgen, Novartis, Takeda and Bristol Myers Squibb); MA: speakers bureau (Janssen); AO: advisory board and consultancy (Amgen and Janssen), and consultancy (Takeda); MVM: honoraria and advisory board (Janssen, Celgene, Takeda and Amgen); RV: research support and consultancy/honoraria (Amgen, Celgene and Takeda), and consultancy/honoraria (Bristol Myers Squibb, Janssen, Karyopham and Abbvie); H Lokhorst: research funding and advisory board (Janssen), and research funding (Genmab); NvdD: research funding (Janssen, Celgene, Amgen and BMS) and advisory board (Janssen, Celgene, Amgen, BMS and Novartis); TM: research funding (Amgen and Celgene); MH: advisory board (Celgene, Janssen, Amgen and Takeda); H Ludwig: speakers bureau (Celgene, Takeda, Amgen and Janssen-Cilag), advisory board (Celgene, Amgen, Janssen-Cilag, AbbVie and Bristol Myers Squibb) and research funding (Takeda and Amgen); MD: consultancy (Amgen, Bristol Myers Squibb, Celgene, Janssen and Takeda) and research funding (Celgene and Janssen); U-HM: advisory board (Amgen and Takeda) and honoraria (Amgen, Celgene, Takeda, Mundipharma, Janssen and Novartis); SZU: advisory board (Amgen, Celgene and Skyline Diagnostics), speakers bureau (Amgen, Celgene and Takeda) and research funding (Amgen, Celgene, Janssen, Sanofi, Pharmacyclics, Array Biopharma and Takeda); PM: advisory board (Celgene, Takeda, Janssen, Novartis and Amgen); LR: honoraria (Janssen and Celgene); all the other authors declare no conflicts of interest.

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Supplementary Information accompanies this paper on the Leukemia website

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Kumar, S., Dimopoulos, M., Kastritis, E. et al. Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: a multicenter IMWG study. Leukemia 31, 2443–2448 (2017). https://doi.org/10.1038/leu.2017.138

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