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Renal failure among multiple myeloma patients utilizing carfilzomib and associated factors in the “real world”

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Abstract

Carfilzomib, a next-generation proteasome inhibitor, improves outcomes in patients with multiple myeloma (MM); however, a proportion of those treated develop renal failure due to adverse event, comorbidity, or myeloma progression. The rate of renal failure and associated risk factors remains unknown in real-world populations. Adults with relapsed/refractory MM who received carfilzomib between the years 2013 and 2016 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases. Renal failure was defined using the corresponding International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) diagnostic codes and procedure codes for dialysis. Patients with a pre-existing diagnosis of renal failure were excluded to distinguish an adverse event from comorbidity. Multivariate cox regression analysis was performed to identify the variables independently associated with the development of renal failure among MM patients utilizing carfilzomib. A total of 1950 patients were included in the analysis. Renal failure developed in 22% of patients during the study period. The median time to development of renal failure from first carfilzomib administration was 1.6 months (range < 0.1–23.3). Increasing age (adjusted hazard ratio [aHR] 1.01 per year, p = 0.018), pre-existing heart failure (aHR 1.50, p = 0.005), and pre-existing chronic kidney disease (aHR 2.00, p < 0.001) were associated with a higher risk of developing renal failure. Renal failure occurred in up to 22% of patients on carfilzomib therapy. The exact cause and mechanism of renal failure cannot be determined from our study and may be multifactorial. Future studies are needed to further understand the cause of renal failure among patients on carfilzomib and devise strategies to mitigate the risk.

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Funding

The Center for Administrative Data Research is supported in part by the Washington University Institute of Clinical and Translational Sciences grant UL1 TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) and Grant Number R24 HS19455 through the Agency for Healthcare Research and Quality (AHRQ).

This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the Applied Research Program, National Cancer Institute; the Office of Research, Development and Information, Centers for Medicare & Medicaid Services; Information Management Services Inc.; and the SEER program tumor registries in the creation of the SEER-MHOS database.

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Authors and Affiliations

  1. Department of Oncology, McMaster University, 699 Concession St., Hamilton, ON, L8V 5C2, Canada

    Hira S. Mian

  2. Department of Medicine, Division of Medical Oncology, Washington University School of Medicine, St. Louis, MO, USA

    Mark A. Fiala, Ravi Vij & Tanya M. Wildes

  3. College for Public Health and Social Justice, Saint Louis University, Saint Louis, MO, USA

    Mark A. Fiala

  4. Department of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Larysa Sanchez

Authors
  1. Hira S. Mian
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  2. Mark A. Fiala
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  4. Ravi Vij
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  5. Tanya M. Wildes
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Contributions

Conception of idea: MF, TW, HM

Acquisition of data: MF

Analysis/interpretation of data: All authors

Manuscript draft: All authors

Revision and final approval: All authors

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Correspondence to Hira S. Mian.

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Conflict of interest

Author HM has received honoraria/consultancy fees from Celgene, Takeda, Sanofi, Amgen, and Janssen. Author MF declares that he has no conflict of interest. Author LS declares that she has no conflict of interest. Author RV has received research support from BMS/Takeda/Sanofi and Honoraria from BMS/Takeda/Sanofi/GSK/Karyopharm/Janssen/Oncopeptides/Securabio. Author TW has received research funding from Janssen and consulting fees from Carevive Systems, Seattle Genetics.

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Mian, H.S., Fiala, M.A., Sanchez, L. et al. Renal failure among multiple myeloma patients utilizing carfilzomib and associated factors in the “real world”. Ann Hematol 100, 1261–1266 (2021). https://doi.org/10.1007/s00277-021-04420-3

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