Autologous stem cell transplantation in newly diagnosed multiple myeloma patients with severe renal failure requiring hemodialysis. A single-center experience

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Abstract

Background. Renal failure (RF) is unfavorable prognostic factor for the multiple myeloma (MM) patients, negatively affecting overall survival. High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is associated with an increased risk of HSCT-related complications and mortality, which may limit its implementation in MM patients with RF, especially in patients with severe RF requiring hemodialysis.

Aim. To analyze the effectiveness and adverse events of high-dose chemotherapy followed by auto-HSCT in newly diagnosed MM patients with severe RF requiring hemodialysis.

Materials and methods. We analyzed the data of 7 newly diagnosed MM patients with severe RF requiring hemodialysis, who received auto-HSCT.

Results. Complete remission achieved 2 (28.6 %) patients, very good partial remission – 4 (57.1 %) patients, partial remission – 1 (14.3 %) patient on the 100th day after auto-HSCT. Complete renal response achieved 6 (85.7 %) patients, 1 (14.3 %) patient remained a minimal renal response. Auto-HSCT led to an improvement in both hematological and renal responses in 1 (14.3 %) patient, hematological response – in 2 (28.6 %) patients. With a median follow-up of 19 months, median progression-free survival and overall survival were 43 and 81 months, respectively. In the early post-transplant period, febrile neutropenia (71.4 %) and grade III–IV mucositis (71.4 %) were most often diagnosed. In the study group of patients, there was no auto-HSCT-related mortality.

Conclusion. Auto-HSCT is an effective and safe method of treating newly diagnosed MM patients with severe RF requiring hemodialysis.

About the authors

Yu. I. Kliuchagina

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Author for correspondence.
Email: klyuchagina92@mail.ru
ORCID iD: 0000-0003-2748-9208

Yulia I. Kliuchagina 

Build. 2, 8 Trubetskaya St., Moscow 119991

Russian Federation

P. A. Zeynalova

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University);
Clinical Hospital “Lapino” of the “Mother and Child” Group of companies

ORCID iD: 0000-0003-1564-424X

Build. 2, 8 Trubetskaya St., Moscow 119991,

111 1st Uspenskoe Shosse, Lapino, Moscow region 143081

Russian Federation

E. G. Gromova

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

ORCID iD: 0000-0002-4633-8301

24 Kashirskoe Shosse, Moscow 115522

Russian Federation

T. T. Valiev

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University);
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

ORCID iD: 0000-0002-1469-2365

Build. 2, 8 Trubetskaya St., Moscow 119991,

24 Kashirskoe Shosse, Moscow 115522

Russian Federation

References

  1. Dimopoulos M.A., Merlini G., Bridoux F. et al. Management of multiple myeloma-related renal impairment: recommendations from the International Myeloma Working Group. Lancet Oncol 2023;24(7):e293–311. doi: 10.1016/S1470-2045(23)00223-1
  2. Dimopoulos M.A., Sonneveld P., Leung N. et al. International Myeloma Working Group recommendations for the diagnosis and management of myeloma-related renal impairment. J Clin Oncol 2016;34(13):1544–57. doi: 10.1200/JCO.2015.65.0044
  3. Chen X., Luo X., Zu Y. et al. Severe renal impairment as an adverse prognostic factor for survival in newly diagnosed multiple myeloma patients. J Clin Lab Anal 2020;34(9):e23416. doi: 10.1002/jcla.23416
  4. Dimopoulos M.A., Delimpasi S., Katodritou E. et al. Significant improvement in the survival of patients with multiple myeloma presenting with severe renal impairment after the introduction of novel agents. Ann Oncol 2014;25(1):195–200. doi: 10.1093/annonc/mdt483
  5. Eleutherakis-Papaiakovou V., Bamias A., Gika D. et al. Renal failure in multiple myeloma: incidence, correlations, and prognostic significance. Leuk Lymphoma 2007;48(2):337–41. doi: 10.1080/10428190601126602
  6. Tsakiris D.J., Stel V.S., Finne P. et al. Incidence and outcome of patients starting renal replacement therapy for end-stage renal disease due to multiple myeloma or light-chain deposit disease: an ERA-EDTA Registry study. Nephrol Dial Transplant 2010;25(4):1200–6. doi: 10.1093/ndt/gfp679
  7. Braet P., Sartò G.V.R., Pirovano M. et al. Treatment of acute kidney injury in cancer patients. Clin Kidney J 2021;15(5):873–84. doi: 10.1093/ckj/sfab292
  8. Bridoux F., Leung N., Belmouaz M. et al. Management of acute kidney injury in symptomatic multiple myeloma. Kidney Int 2021;99(3):570–80. doi: 10.1016/j.kint.2020.11.010
  9. Leung N., Bridoux F., Batuman V. et al. The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group [published correction appears in Nat Rev Nephrol 2019;15(2):121]. Nat Rev Nephrol 2019;15(1):45–59. PMID: 30510265. doi: 10.1038/s41581-018-0077-4
  10. Dimopoulos M.A., Kastritis E., Rosinol L. et al. Pathogenesis and treatment of renal failure in multiple myeloma. Leukemia 2008;22(8):1485–93. doi: 10.1038/leu.2008.131
  11. Ying W.Z., Sanders P.W. Mapping the binding domain of immunoglobulin light chains for Tamm–Horsfall protein. Am J Pathol 2001;158(5):1859–66. doi: 10.1016/S0002-9440(10)64142-9
  12. Stringer S., Basnayake K., Hutchison C., Cockwell P. Recent advances in the pathogenesis and management of cast nephropathy (myeloma kidney). Bone Marrow Res 2011;2011:493697. doi: 10.1155/2011/493697
  13. Gonsalves W.I., Leung N., Rajkumar S.V. et al. Improvement in renal function and its impact on survival in patients with newly diagnosed multiple myeloma. Blood Cancer J 2015;5(3):e296. doi: 10.1038/bcj.2015.20
  14. Rekhtina I.G., Mendeleeva L.P. Current approaches to treating of patients with multiple myeloma with renal failure: questions and proofs. Terapevticheskii arkhiv = Therapeutic Archive. 2017;89(7):112–7. (In Russ.) doi: 10.17116/terarkh2017897112-117
  15. Bachmann F., Schreder M., Engelhardt M. et al. Kinetics of renal function during induction in newly diagnosed multiple myeloma: results of two prospective studies by the German Myeloma Study Group DSMM. Cancers (Basel) 2021;13(6):1322. doi: 10.3390/cancers13061322
  16. Robak P., Robak T. Bortezomib for the treatment of hematologic malignancies: 15 years later. Drugs R D 2019:73–92. doi: 10.1007/s40268-019-0269-9
  17. Oortgiesen B.E., Azad R., Hemmelder M.H. et al. The impact of the introduction of bortezomib on dialysis independence in multiple myeloma patients with renal impairment: a nationwide Dutch population-based study. Haematologica 2018;103(7):e311–4. doi: 10.3324/haematol.2017.184754
  18. Ryabukhina Yu.E., Zeynalova P.A., Timofeeva O.L. et al. Use of daratumumab in therapy of patients with newly diagnosed multiple myeloma complicated by dialysis-dependent kidney failure: literature review and clinical observation. MD-Onco 2023;3(3):48–56. (In Russ.). doi: 10.17650/2782-3202-2023-3-3-48-56
  19. Dimopoulos M.A., Moreau P., Terpos E. et al. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up [published correction appears in Ann Oncol 2022;33(1):117]. Ann Oncol 2021;32(3):309–22. doi: 10.1016/j.annonc.2021.10.001
  20. Augeul-Meunier K., Chretien M.L., Stoppa A.M. 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 Transplant 2018;53(6):749–55. doi: 10.1038/s41409-018-0122-8
  21. Kumar L., Chellapuram S.K., Dev R. et al. Induction therapy with novel agents and autologous stem cell transplant overcomes the adverse impact of renal impairment in multiple myeloma. Clin Hematol Int 2019;1(4):205–19. doi: 10.2991/chi.d.190805.003
  22. Li A., Atenafu E., Bernard R. et al. Toxicity and survival outcomes of autologous stem cell transplant in multiple myeloma patients with renal insufficiency: an institutional comparison between two eras. Bone Marrow Transplant 2020;55(3):578–85. doi: 10.1038/s41409-019-0697-8
  23. Parikh G.C., Amjad A.I., Saliba R.M. et al. Autologous hematopoietic stem cell transplantation may reverse renal failure in patients with multiple myeloma. Biol Blood Marrow Transplant 2009;15(7):812–6. doi: 10.1016/j.bbmt.2009.03.021
  24. Mahindra A., Hari P., Fraser R. 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 Transplant 2017;52(12):1616–22. doi: 10.1038/bmt.2017.198
  25. Levey A.S., Stevens L.A., Schmid C.H. et al. A new equation to estimate glomerular filtration rate [published correction appears in Ann Intern Med 2011;155(6):408]. Ann Intern Med 2009;150(9): 604–12. doi: 10.7326/0003-4819-150-9-200905050-00006
  26. Rajkumar S.V., Dimopoulos M.A., Palumbo A. et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014;15(12):e538–48. doi: 10.1016/S1470-2045(14)70442-5
  27. Kumar S., Paiva B., Anderson K.C. et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 2016:e328–46. doi: 10.1016/S1470-2045(16)30206-6
  28. Gromova E.G., Zeynalova P.A., Lubimova N.V. et al. The experience of free light chains of immunoglobulin elimination in patients with monoclonal gammopathies. Onkogematologiya = Oncohematology 2019;14(2):8–12. (In Russ.). doi: 10.17650/1818-8346-2019-14-2-8-12
  29. Freites-Martinez A., Santana N., Arias-Santiago S., Viera A. Using the common terminology criteria for adverse events (CTCAE – Version 5.0) to evaluate the severity of adverse events of anticancer therapies. Actas Dermosifiliogr (Engl Ed) 2021;112(1):90–2. doi: 10.1016/j.ad.2019.05.009
  30. Zhu W., Chen W. Bortezomib-based treatment for multiple myeloma patients with renal impairment: a systematic review and meta-analysis of observational studies. Medicine (Baltimore) 2016;95(46):e5202. doi: 10.1097/MD.0000000000005202
  31. Scheid C., Sonneveld P., Schmidt-Wolf I.G. et al. Bortezomib before and after autologous stem cell transplantation overcomes the negative prognostic impact of renal impairment in newly diagnosed multiple myeloma: a subgroup analysis from the HOVON-65/ GMMG-HD4 trial. Haematologica 2014;99(1):148–54. doi: 10.3324/haematol.2013.087585
  32. Sweiss K., Patel S., Culos K. et al. Melphalan 200mg/m2 in patients with renal impairment is associated with increased short-term toxicity but improved response and longer treatment-free survival. Bone Marrow Transplant 2016;51(10):1337–41. doi: 10.1038/bmt.2016.136
  33. 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 2023;58(4):424–9. doi: 10.1038/s41409-023-01915-7
  34. St Bernard R., Chodirker L., Masih-Khan E. et al. Efficacy, toxicity and mortality of autologous SCT in multiple myeloma patients with dialysis-dependent renal failure. Bone Marrow Transplant 2015;50(1):95–9. doi: 10.1038/bmt.2014.226
  35. Firsova M.V., Mendeleeva L.P., Solov’ev M.V. et al. Autologous hematopoietic stem cell transplantation in multiple myeloma with renal impairment. Klinicheskaya onkogematologiya = Clinical oncohematology 2022;15(1):97–106. (In Russ.). doi: 10.21320/2500-2139-2022-15-1-97-106

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