Abstract
The role of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) in the treatment of myeloma (MM) patients with severe and/or dialysis-dependent renal impairment remains uncertain. We report on the outcomes of 110 patients (median age 57 years) who had become dialysis-dependent pre-ASCT and who underwent a first ASCT between 1997 and 2017. Sixty-three (57%) patients had light chain MM. All patients required dialysis (94% hemodialysis and 6% peritoneal). Forty-four of 71 (62%) patients received bortezomib-based induction regimens and 42 (39%) patients had achieved at least a very good partial response (VGPR) pre-ASCT. Melphalan dosing was as follows: ≤140 mg/m2 (82%), and >140 mg/m2 (18%). The median PFS after ASCT was 35 months (95% CI: 21.5–42.2) and the median OS 102 months (95% CI: 70.4–129.1). At 1, 2, and 5 years after ASCT, 8% (95% CI 3–14%), 13% (6–20%), and 20% (12–29%) of patients, respectively, had achieved dialysis independence. In multivariate analyses of OS and PFS including age at ASCT, response at ASCT, and year of ASCT, younger age at ASCT and better response at ASCT (CR/VGPR/PR vs. MR/SD/progression) were significantly associated with better OS and PFS.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Data availability
The final analysis dataset is available upon request to the Working Party chair.
References
Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, et al. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. N. Engl J Med. 2017;376:1311–20. https://doi.org/10.1056/NEJMoa1611750
Gay F, Oliva S, Petrucci MT, Conticello C, Catalano L, Corradini P, et al. Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial. Lancet Oncol. 2015;16:1617–29. https://doi.org/10.1016/S1470-2045(15)00389-7.
Cavo M, Gay F, Beksac M, Dimopoulos MA, Pantani L, Petrucci MT, et al. Upfront autologous hematopoietic stem-cell transplantation improves overall survival in comparison with bortezomib-based intensification therapy in newly diagnosed multiple myeloma: long-term follow-up analysis of the randomized Phase 3 EMN02/HO95 Study. Blood. 2020;1361:37–38. https://doi.org/10.1182/blood-2020-137575
Richardson PG, Jacobus SJ, Weller EA, Hassoun H, Lonial S, Raje NS, et al. Triplet therapy, transplantation, and maintenance until progression in myeloma. N. Engl J Med. 2022;387:132–47. https://doi.org/10.1056/NEJMoa2204925.
Badros A, Barlogie B, Siegel E, Roberts J, Langmaid C, Zangari M, et al. Results of autologous stem cell transplant in multiple myeloma patients with renal failure. Br J Haematol. 2001;114:822–9. https://doi.org/10.1046/j.1365-2141.2001.03033.x
Augeul-Meunier K, Chretien ML, Stoppa AM, Karlin L, Benboubker L, Diaz JMT, et al. Extending autologous transplantation as first line therapy in multiple myeloma patients with severe renal impairment: a retrospective study by the SFGM-TC. Bone Marrow Transpl. 2018;53:749–55. https://doi.org/10.1038/s41409-018-0122-8.
Auner HW, Iacobelli S, Sbianchi G, Knol-Bout C, Blaise D, Russell NH, et al. Melphalan 140 mg/m(2) or 200 mg/m(2) for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party. Haematologica. 2018;103:514–21. https://doi.org/10.3324/haematol.2017.181339.
Eleutherakis-Papaiakovou V, Bamias A, Gika D, Simeonidis A, Pouli A, Anagnostopoulos A, et al. Renal failure in multiple myeloma: incidence, correlations, and prognostic significance. Leuk Lymphoma. 2007;48:337–41. https://doi.org/10.1080/10428190601126602
Dimopoulos MA, Kastritis E, Rosinol L, Blade J, Ludwig H. Pathogenesis and treatment of renal failure in multiple myeloma. Leukemia. 2008;22:1485–93. https://doi.org/10.1038/leu.2008.131.
Dimopoulos MA, Terpos E. Renal insufficiency and failure. Hematol Am Soc Hematol Educ Program. 2010;2010:431–6. https://doi.org/10.1182/asheducation-2010.1.431
Dimopoulos MA, Sonneveld P, Leung N, Merlini G, Ludwig H, Kastritis E, et al. International Myeloma Working Group recommendations for the diagnosis and management of myeloma-related renal impairment. J Clin Oncol. 2016;34:1544–57. https://doi.org/10.1200/JCO.2015.65.0044.
Mahindra A, Hari P, Fraser R, Fei M, Huang J, Berdeja J, et al. Autologous hematopoietic cell transplantation for multiple myeloma patients with renal insufficiency: a center for international blood and marrow transplant research analysis. Bone Marrow Transpl. 2017;52:1616–22. https://doi.org/10.1038/bmt.2017.198.
Leung N. To biopsy or not to biopsy, that is the question in myeloma cast nephropathy. Nephrol Dial Transpl. 2016;31:1–3. https://doi.org/10.1093/ndt/gfv294.
Rajkumar SV. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. Am J Hematol. 2022;97:1086–107. https://doi.org/10.1002/ajh.26590.
Raab MS, Breitkreutz I, Hundemer M, Benner A, Klaus J, Hegenbart U, et al. The outcome of autologous stem cell transplantation in patients with plasma cell disorders and dialysis-dependent renal failure. Haematologica. 2006;91:1555–8.
Waszczuk-Gajda A, Lewandowski Z, Drozd-Sokolowska J, Boguradzki P, Dybko J, Wrobel T, et al. Autologous peripheral blood stem cell transplantation in dialysis-dependent multiple myeloma patients-DAUTOS Study of the Polish Myeloma Study Group. Eur J Haematol. 2018;101:475–85. https://doi.org/10.1111/ejh.13101.
Matsue K, Fujiwara H, Iwama K, Kimura S, Yamakura M, Takeuchi M. Reversal of dialysis-dependent renal failure in patients with advanced multiple myeloma: single institutional experiences over 8 years. Ann Hematol. 2010;89:291–7. https://doi.org/10.1007/s00277-009-0813-8.
Breitkreutz I, Heiss C, Perne A, Beimler J, Jager D, Egerer G, et al. Bortezomib improves outcome after SCT in multiple myeloma patients with end-stage renal failure. Bone Marrow Transpl. 2014;49:1371–5. https://doi.org/10.1038/bmt.2014.165.
St Bernard R, Chodirker L, Masih-Khan E, Jiang H, Franke N, Kukreti V, et al. Efficacy, toxicity and mortality of autologous SCT in multiple myeloma patients with dialysis-dependent renal failure. Bone Marrow Transpl. 2015;50:95–99. https://doi.org/10.1038/bmt.2014.226.
Chanan-Khan AA, Kaufman JL, Mehta J, Richardson PG, Miller KC, Lonial S, et al. Activity and safety of bortezomib in multiple myeloma patients with advanced renal failure: a multicenter retrospective study. Blood. 2007;109:2604–6. https://doi.org/10.1182/blood-2006-09-046409.
Dimopoulos MA, Roussou M, Gkotzamanidou M, Nikitas N, Psimenou E, Mparmparoussi D, et al. The role of novel agents on the reversibility of renal impairment in newly diagnosed symptomatic patients with multiple myeloma. Leukemia. 2013;27:423–9. https://doi.org/10.1038/leu.2012.182.
Cleary J, Drennan J. Quality of life of patients on haemodialysis for end-stage renal disease. J Adv Nurs. 2005;51:577–86. https://doi.org/10.1111/j.1365-2648.2005.03547.x
Author information
Authors and Affiliations
Contributions
AW-G designed the study, interpreted the data, and wrote the first draft of the manuscript. The data was extracted and compiled by TS and the statistical analysis performed by LG and LCDW. PJH, MB, DPMcL, and SS interpreted the data and edited the manuscript. AI, ZNO, JAS, MA, CEB, JN, MS, SP, VP, AG, TC, GVG, JML, TK, JD-S, KR, and IYA reviewed the manuscript and provided clinical data. All authors approved the final version of the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Waszczuk-Gajda, A., Gras, L., de Wreede, L.C. et al. Safety and efficacy of autologous stem cell transplantation in dialysis-dependent myeloma patients—The DIADEM study from the chronic malignancies working party of the EBMT. Bone Marrow Transplant 58, 424–429 (2023). https://doi.org/10.1038/s41409-023-01915-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41409-023-01915-7