Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma with Renal Impairment

AUTOIMMUNE THROMBOCYTOPENIA ,

MV Firsova, LP Mendeleeva, MV Solov’ev, DA Mironova, LA Kuzmina, VG Savchenko

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Maiya Valerevna Firsova, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: firs-maia@yandex.ru

For citation: Firsova MV, Mendeleeva LP, Solov’ev MV, et al. Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma with Renal Impairment. Clinical oncohematology. 2022;15(1):97–106. (In Russ).

DOI: 10.21320/2500-2139-2022-15-1-97-106

ABSTRACT

Aim. To study the efficacy and adverse event spectrum of high-dose chemotherapy with subsequent autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients with acute renal impairment, including hemodialysis (HD) dependence.

Materials & Methods. The retrospective single-center study enrolled 64 MM patients (30 men and 34 women) with renal impairment, aged 19–65 years (median 54 years), who received auto-HSCT in the period from 2013 to 2019. Newly diagnosed patients had a median creatinine of 462 µmol/L and a median glomerular filtration rate of 10 ml/min/1,73 m2 (CKD-EPI). HD dependence was reported in 23 (36 %) patients on diagnosis date. As a result of the induction therapy, in 13 (57 %) out of 23 patients HD could be discontinued. Prior to auto-HSCT, overall antitumor response was 91 % (complete remission was 45 %), overall renal response was 80 % (complete renal response was 28 %). In the course of auto-HSCT 10 patients remained HD dependent. Two groups were analyzed: “HD–” (program HD-independent patients during auto-HSCT, n = 54) and “HD+” (program HD-dependent recipients of auto-HSCT, n = 10).

Results. Herpes virus infection reactivation and reversible toxic encephalopathy were observed significantly more often in “HD+” than in “HD–” group (30 % vs. 6 %, p = 0.04 and 20 % vs. 0 %, p = 0.02, respectively). HD-dependent patients required red blood cell transfusion significantly more often than HD-independent patients (100 % vs. 35 % of cases; p = 0.0001). In 100 days after auto-HSCT, overall antitumor response increased from 91 % to 96 %, the rate of complete remission increased from 45 % to 64 %. After auto-HSCT the rate of complete renal response increased from 28 % to 34 %, however, overall renal response remained within the range of 80 %. After auto-HSCT, in a single case HD was discontinued. As a result of the treatment, 14 (61 %) patients became HD-independent. Transplantation-associated mortality was not reported. During median follow-up of 48 months, 5-year overall survival was 70 % and 5-year disease-free survival was 42 %.

Conclusion. Auto-HSCT is a feasible, safe, and effective treatment of MM patients with acute renal impairment. Induction therapy with subsequent auto-HSCT resulted in less need for HD which was 36 % at MM onset and 14 % on completing the treatment.

Keywords: multiple myeloma, auto-HSCT, hemodialysis, acute renal impairment, cast nephropathy.

Received: July 8, 2021

Accepted: November 28, 2021

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REFERENCES

  1. Dimopoulos MA, 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.
  2. Knudsen LM, Hjorth M, Hippe E. Renal failure in multiple myeloma: reversibility and impact on the prognosis. Nordic Myeloma Study Group. Eur J Haematol. 2000;65(3):175–81. doi: 10.1034/j.1600-0609.2000.90221.x.
  3. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538–е548. doi: 10.1016/S1470-2045(14)70442-5.
  4. Yadav P, Cook M, Cockwell P. Current Trends of Renal Impairment in Multiple Myeloma. Kidney Dis (Basel). 2016;1(4):241–57. doi: 10.1159/000442511.
  5. Blade J, Fernandez-Llama P, Bosch F, et al. Renal failure in multiple myeloma: presenting features and predictors of outcome in 94 patients from a single institution. Arch Intern Med. 1998;158(17):1889–93. doi: 10.1001/archinte.158.17.1889.
  6. Mendeleeva LP, Solovev M, Alexeeva A, et al. Multiple Myeloma in Russia (First Results of the Registration Trial). Blood. 2017;130(S1):5408.
  7. Kastritis E, Terpos E, Dimopoulos MA. Current treatments for renal failure due to multiple myeloma. Expert Opin Pharmacother. 2013;14(11):1477–95. doi: 10.1517/14656566.2013.803068.
  8. Sengul S, Zwizinski C, Simon EE, et al. Endocytosis of light chains induces cytokines through activation of NF-kappaB in human proximal tubule cells. Kidney Int. 2002;62(6):1977–88. doi: 10.1046/j.1523-1755.2002.00660.x.
  9. Рехтина И.Г., Казарина Е.В., Столяревич Е.С. и др. Морфологические и иммуногистохимические предикторы почечного ответа на терапию у пациентов с миеломной каст-нефропатией и острым повреждением почек с потребностью в диализе. Терапевтический архив. 2020;92(7):63–9. doi: 10.26442/00403660.2020.07.000776.
    [Rekhtina IG, Kazarina EV, Stolyarevich ES, et al. Morphological and immunohistochemical predictors of renal response to therapy patients with myeloma cast nephropathy and dialysis-dependent acute kidney injury. Terapevticheskii arkhiv. 2020;92(7):63–9. doi: 10.26442/00403660.2020.07.000776. (In Russ)]
  10. Dimopoulos MA, 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.
  11. Khan R, Apewokin S, Grazziutti M, et al. Renal insufficiency retains adverse prognostic implications despite renal function improvement following Total Therapy for newly diagnosed multiple myeloma. Leukemia. 2015;29(5):1195–201. doi: 10.1038/leu.2015.15.
  12. Uttervall K, Duru AD, Lund J, et al. The use of novel drugs can effectively improve response, delay relapse and enhance overall survival in multiple myeloma patients with renal impairment. PLoS One. 2014;9(7):e101819. doi: 10.1371/journal.pone.0101819.
  13. Badros A, Barlogie B, Siegel E, et al. Results of autologous stem cell transplant in multiple myeloma patients with renal failure. Br J Haematol. 2001;114(4):822–9. doi: 10.1046/j.1365-2141.2001.03033.x.
  14. Lee CK, Zangari M, Barlogie B, et al. Dialysis-dependent renal failure in patients with myeloma can be reversed by high-dose myeloablative therapy and autotransplant. Bone Marrow Transplant. 2004;33(8):823–8. doi: 10.1038/sj.bmt.1704440.
  15. Фирсова М.В., Менделеева Л.П., Соловьев М.В. и др. Трансплантация аутологичных стволовых клеток крови больным множественной миеломой, осложненной диализ-зависимой почечной недостаточностью. Терапевтический архив. 2020;92(7):70–6. doi: 10.26442/00403660.2020.07.000777.
    [Firsova MV, Mendeleeva LP, Solovev MV, et al. Autologous haematopoietic stem cell transplantation in patients with multiple myeloma complicated by dialysis-dependent renal failure. Terapevticheskii arkhiv. 2020;92(7):70–6. doi: 10.26442/00403660.2020.07.000777. (In Russ)]
  16. Durie BG, Harousseau JL, Miguel JS, et al. International Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia. 2006;20(9):1467–73. doi: 10.1038/sj.leu.2404284.
  17. Dimopoulos MA, Terpos E, Chanan-Khan A, et al. Renal impairment in patients with multiple myeloma: a consensus statement on behalf of the International Myeloma Working Group. J Clin Oncol. 2010;28(33):4976–84. doi: 10.1200/JCO.2010.30.8791.
  18. Waszczuk-Gajda A, Lewandowski Z, Drozd-Sokolowska J, 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(4):475–85. doi: 10.1111/ejh.13101.
  19. Ecotiere L, Thierry A, Debiais-Delpech C, et al. Prognostic value of kidney biopsy in myeloma cast nephropathy: a retrospective study of 70 patients. Nephrol Dial Transplant. 2016;31(1):64–72. doi: 10.1093/ndt/gfv283.
  20. Roussou M, Kastritis E, Migkou M, et al. Treatment of patients with multiple myeloma complicated by renal failure with bortezomib-based regimens. Leuk Lymphoma. 2008;49(5):890–5. doi: 10.1080/10428190801930506.
  21. 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.
  22. Li AY, Atenafu EG, Bernard RS, 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 GC, Amjad AI, Saliba RM, 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. Tosi P, Zamagni E, Ronconi S, et al. Safety of autologous hematopoietic stem cell transplantation in patients with multiple myeloma and chronic renal failure. Leukemia. 2000;14(7):1310–3. doi: 10.1038/sj.leu.2401819.
  25. Bird JM, Fuge R, Sirohi B, et al. The clinical outcome and toxicity of high-dose chemotherapy and autologous stem cell transplantation in patients with myeloma or amyloid and severe renal impairment: a British Society of Blood and Marrow Transplantation study. Br J Haematol. 2006;134(4):385–90. doi: 10.1111/j.1365-2141.2006.06191.x.
  26. Knudsen LM, Nielsen B, Gimsing P, Geisler C. Autologous stem cell transplantation in multiple myeloma: outcome in patients with renal failure. Eur J Haematol. 2005;75(1):27–33. doi: 10.1111/j.1600-0609.2005.00446.x.
  27. Mohyuddin GR, Abbasi S, Okoniewski M, et al. Inpatient mortality of patients with multiple myeloma and renal impairment undergoing autologous stem cell transplantation. Eur J Haematol. 2020;105(5):571–7. doi: 10.1111/ejh.13487.
  28. Rios-Tamayo R, Sainz J, Martinez-Lopez J, et al. Early mortality in multiple myeloma: the time-dependent impact of comorbidity: A population-based study in 621 real-life patients. Am J Hematol. 2016;91(7):700–4. doi: 10.1002/ajh.24389.
  29. Boenink R, Stel VS, Waldum-Grevbo BE, et al. Data from the ERA-EDTA Registry were examined for trends in excess mortality in European adults on kidney replacement therapy. Kidney Int. 2020;98(4):999–1008. doi: 10.1016/j.kint.2020.05.039.
  30. Antlanger M, Dust T, Reiter T, et al. Impact of renal impairment on outcomes after autologous stem cell transplantation in multiple myeloma: a multi-center, retrospective cohort study. BMC Cancer. 2018;18(1):1008. doi: 10.1186/s12885-018-4926-0.