Original Article

Multiple Myeloma, Gammopathies

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

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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.

Author information

Affiliations

  1. Department of Hematology, Mayo Clinic Rochester, Rochester, MN, USA

    • S K Kumar
  2. School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

    • M A Dimopoulos
    • , E Kastritis
    •  & E Terpos
  3. Division of Hematology, Karolinska Institutet, Karolinska University Hospital at Huddinge, Stockholm, Sweden

    • H Nahi
  4. National Center for Tumor Diseases Heidelberg, Heidelberg, Germany

    • H Goldschmidt
  5. Department Med. V, University Hospital Heidelberg, Heidelberg, Germany

    • H Goldschmidt
    •  & J Hillengass
  6. Oncologie hematologique et therapie cellulaire, chu de poitiers, Poitiers, France

    • X Leleu
  7. Department of Hematology, Ankara University School of Medicine, Ankara, Turkey

    • M Beksac
  8. Hematologic Malignancies Program, H. Lee Moffitt Cancer Center, Tampa, FL, USA

    • M Alsina
  9. Department of Hematology, Skane University Hospital, Malmö, Sweden

    • A Oriol
    •  & I Turesson
  10. Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy

    • M Cavo
  11. Department of Hematology, University Hospital of Salamanca (HUS/IBSAL), Salamanca, Spain

    • E M Ocio
  12. Department of Hematolgy, Hospital Universitario de Salamanca, Salamanca, Spain

    • M V Mateos
  13. Massachusetts General Hospital, Boston, MA

    • E K O'Donnell
  14. Division of Oncology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA

    • R Vij
  15. Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands

    • H M Lokhorst
  16. VU University Medical Center, Amsterdam, The Netherlands

    • N W C J van de Donk
  17. Department of Hematology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, The Republic of Korea

    • C Min
  18. Weill Cornell Medical College, New York, NY, USA

    • T Mark
  19. Department of Hematology, Skåne University Hospital, Lund University, Lund, Sweden

    • M Hansson
  20. Department of Medicine, Center of Oncology, Hematology and Palliative Care, Wilhelminen Cancer Research Institute, Wilhelminenspital, Vienna, Austria

    • H Ludwig
  21. Department of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    • S Jagannath
  22. Myeloma Study Group, Belgian Hematological Society, Brussels, Belgium

    • M Delforge
  23. Department of Haematology, North West London NHS Trust, NPH Hospital, London, UK

    • C Kyriakou
  24. Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI, USA

    • P Hari
  25. Section of Hematology and Coagulation, Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden

    • U Mellqvist
  26. Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute/Carolinas HealthCare System, Charlotte, NC, USA

    • S Z Usmani
  27. Department of Hematology and Bone Marrow Transplantation, University of Medical Sciences in Poznan, Poland, Poznan, Poland

    • D Dytfeld
  28. Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA

    • A Z Badros
  29. Department of Hematology, Nantes University Hospital, Nantes, France

    • P Moreau
  30. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, The Republic of Korea

    • K Kim
  31. Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain

    • P R Otero
  32. Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, The Republic of Korea

    • J H Lee
  33. Division of Haematology, McGill University Health Center, Montreal, QC, Canada

    • C Shustik
  34. McGill University, Montreal, QC, Canada

    • D Waller
  35. Department of Haematology-Oncology, National University Health Systems, Singapore

    • W J Chng
  36. Department of Hematology, Tokushima Prefectural Central Hospital, Tokushima, Japan

    • S Ozaki
  37. Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanamdo, The Republic of Korea

    • J-J Lee
  38. Hospital Dr. Peset, Valencia, Spain

    • J de la Rubia
  39. HematologicOncology Clinic, Center for Specific Organs, National Cancer Center, Goyang, South Korea

    • H S Eom
  40. Department of Hematology, Hospital Clinic iProvincial, Barcelona, Spain

    • L Rosinol
  41. Hospital Universitario 12 de Octubre, Madrid, Spain

    • J J Lahuerta
  42. Institut Català d'Oncologia, Hospital Duran i Reynals, Barcelona, Spain

    • A Sureda
  43. Yonsei University College of Medicine, Severance Hospital, Seoul, The Republic of Korea

    • J S Kim
  44. Samuel Oschin Comprehensive Cancer Institute, CedarsSinai Outpatient Cancer Center, Los Angeles, CA, USA

    • B G M Durie

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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.

Corresponding author

Correspondence to S K Kumar.

Supplementary information

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  1. 1.

    Supplementary Table

Supplementary Information accompanies this paper on the Leukemia website (http://www.nature.com/leu)