Efficacy of Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Patients Aged over 60 Years

AUTOIMMUNE THROMBOCYTOPENIA

II Kostroma1, VA Yudina1,2, RR Sabitova1, ES Stepchenkova3,4, ZhV Chubukina1, SS Bessmeltsev1, SV Sidorkevich1, SV Gritsaev1

1 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya ul., Saint Petersburg, Russian Federation, 191024

2 VA Almazov National Medical Research Center, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341

3 Saint Petersburg State University, 7/9 Universitetskaya nab., Saint Petersburg, Russian Federation, 199034

4 NI Vavilov Institute of General Genetics, Saint Petersburg branch, 7/9 Universitetskaya nab., Saint Petersburg, Russian Federation, 199034

For correspondence: Ivan Ivanovich Kostroma, MD, PhD, 16 2-ya Sovetskaya ul., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)717-54-68; e-mail: obex@rambler.ru

For citation: Kostroma II, Yudina VA, Sabitova RR, et al. Efficacy of Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Patients Aged over 60 Years. Clinical oncohematology. 2023;16(3):287–93. (In Russ).

DOI: 10.21320/2500-2139-2023-16-3-287-293

ABSTRACT

Aim. To compare toxicity and efficacy of high-dose melphalan chemotherapy with subsequent autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients aged under and over 60 years.

Materials & Methods. The retrospective analysis was conducted on the data of 107 MM patients, 78 of them were aged under 60 years (median 54 years), and 29 of them were aged 61 years and older (median 63 years). All patients received auto-HSCT in the period of 2017–2022. Single and tandem auto-HSCT were performed in 92 and 15 patients, respectively. Patients with tandem auto-HSCT (n = 15), lost to follow-up patients (n = 8), and patients who died during early post-transplant period (n = 4) were excluded from survival analysis. Survival rates were calculated based on the date of auto-HSCT.

Results. A comparative evaluation of the results in two age groups showed a significant difference in the number of patients treated with ixazomib during the induction period (р = 0.019) and cyclophosphamide 3 g/m2 as part of auto-HSC mobilization (р = 0.014), as well as 200 or 140 mg/m2 melphalan as part of conditioning regimen (р = 0.039 and р = 0.009, respectively). With a follow-up median of 13 months (range 1–57 months), the median progression-free survival in the groups ≤ 60 years vs. > 60 years was 32 and 47 months, respectively (hazard ratio [HR] 0.688; 95% confidence interval [95% CI] 0.270–1.754; p = 0.704). The median overall survival in patients aged under 60 years appeared to be 57 months, it was not reached in patients aged 61 years and older (HR 0.689; 95% CI 0.169–2.803; р = 0.577).

Conclusion. The results of the study suggest that all newly diagnosed MM patients aged under 70 years should be regarded as being eligible for auto-HSCT.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, elderly patients.

Received: March 7, 2023

Accepted: June 8, 2023

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REFERENCES

  1. Бессмельцев С.С. Множественная миелома: диагностика и терапия (часть 1). Вестник гематологии. 2022;18(2):4–26.
    [Bessmeltsev SS. Multiple myeloma: diagnosis and therapy (part 1). Vestnik gematologii. 2022;18(2):4–26. (In Russ)]
  2. Множественная миелома. Клинические рекомендации 2020 (электронный документ). Доступно по: www.oncology-association.ru/mnozhestvennaja_myeloma.pdf. Ссылка активна на 27.02.2023.
    [Multiple myeloma. Clinical guidelines 2020 (Internet). Available from: oncology-association.ru/mnozhestvennaja_myeloma.pdf. Accessed 27.02.2023. (In Russ)]
  3. Dimopoulos M, Moreau P, Terpos E, et al. Multiple myeloma: EHA-ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32(3):309–22. doi: 10.1016/j.annonc.2020.11.014.
  4. Rajkumar SV. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. Am J Hematol. 2022;97(8):1086–107. doi: 10.1002/ajh.26590.
  5. Кострома И.И., Сидорова Ж.Ю., Семенова Н.Ю. и др. Возможные предикторы и качество ответа после трансплантации аутологичных гемопоэтических стволовых клеток при множественной миеломе. Клиническая онкогематология. 2021;14(3):333–9. doi: 10.21320/2500-2139-2021-14-3-333-339.
    [Kostroma II, Sidorova ZhYu, Semenova NYu, et al. Potential Predictors and Response Quality after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma. Clinical oncohematology. 2021;14(3):333–9. doi: 10.21320/2500-2139-2021-14-3-333-339. (In Russ)]
  6. Beksac M, Hayden Upfront autologous transplantation still improving outcomes in patients with multiple myeloma. Lancet Haematol. 2023;10(2):80–2. doi: 10.1016/S2352-3026(22)00360-X.
  7. Richardson P, Jacobus S, et al. Triplet therapy, transplantation, and maintenance until progression in myeloma. N Engl J Med. 2022;387(2):132–47. doi: 10.1056/NEJMoa22049.
  8. Afram G, Chaireti R, Uttervall K, et al. Conditioning with melphalan 200 mg/m2 and subsequent ASCT improves progression-free and overall survival in elderly myeloma patients compared to standard of care. Eur J Haematol. 2022;109(6):749–54. doi: 10.1111/ejh.13861.
  9. Garderet L, Beohou E, Caillot D, et al. Upfront autologous stem cell transplantation for newly diagnosed elderly multiple myeloma patients: a prospective multicenter study. Haematologica. 2016;101(11):1390–7. doi: 10.3324/haematol.2016.150334.
  10. Ghilardi G, Pabst T, Jeker B, et al. Melphalan dose in myeloma patients ≥ 65 years of age undergoing high-dose therapy and autologous stem cell transplantation: a multicentric observational registry study. Bone Marrow Transplant. 2019;54(7):1029–37. doi: 1038/s41409-018-0379-y.
  11. Kumar L, Sahoo R, Kumar S, et al. Autologous stem cell transplant for multiple myeloma: Impact of melphalan dose on the transplant outcome. Leuk Lymphoma. 2023;64(2):378–87. doi: 10.1080/10428194.2022.2148214.
  12. Mian H, Mian O, Rochwerg B, et al. Autologous stem cell transplant in older patients (age ≥ 65) with newly diagnosed multiple myeloma: A systematic review and meta-analysis. J Geriatr Oncol. 2020;11(1):93–9. doi: 10.1016/j.jgo.2019.05.014.
  13. Pawlyn C, Cairns D, Menzies T, et al. Autologous stem cell transplantation is safe and effective for fit older myeloma patients: exploratory results from the Myeloma XI trial. Haematologica 2022;107(1):231–42. doi: 10.3324/haematol.2020.262360.
  14. Кострома И.И., Жернякова А.А., Запреева И.М. и др. Ретроспективный анализ выживаемости больных множественной миеломой после трансплантации аутологичных гемопоэтических стволовых клеток. Клиническая онкогематология. 2021;14(1):73–9. doi: 10.21320/2500-2139-2021-14-1-73-79.
    [Kostroma II, Zhernyakova AA, Zapreeva IM, et al. Retrospective Survival Analysis of Multiple Myeloma Patients after Autologous Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2021;14(1):73–9. doi: 10.21320/2500-2139-2021-14-1-73-79. (In Russ)]
  15. Жернякова А.А., Ионова Т.И., Грицаев С.В. Оценка качества жизни при множественной миеломе и ее интерпретация в клинической практике. Вестник межнационального центра исследования качества жизни. 2021;37–38:69–79.
    [Zhernyakova AA, Ionova TI, Gritsaev SV. Quality of life assessment in patients with multiple myeloma and its interpretation in clinical practice. Vestnik mezhnatsional’nogo tsentra issledovaniya kachestva zhizni. 2021;37–38:69–79. (In Russ)]
  16. Жернякова А.А., Кострома И.И., Рыбакова Л.П. и др. Параметры качества жизни, тяжесть симптомов и концентрация малонового диальдегида в сыворотке крови у пациентов с множественной миеломой в посттрансплантационном периоде. Вестник гематологии. 2020;16(2):36–43.
    [Zhernyakova AA, Kostroma II, Rybakova LP, et al. Quality of life, symptom burden, and serum malonic dialdehyde concentration in multiple myeloma patients after stem cell transplantation. Vestnik gematologii. 2020;16(2):36–43. (In Russ)]
  17. Nunnelee J, Cottini F, Zhao Q, et al. Improvement in post-autologous stem cell transplant survival of multiple myeloma patients: a long-term institutional experience. Cancers (Basel). 2022;14(9):2277. doi: 10.3390/cancers14092277.
  18. Revannasiddaiah S, Nagaraju P, Palassery R, et al. The limited use of autologous hematopoietic stem cell transplant for fit older patients with multiple myeloma in India: a retrospective analysis. J Egypt Natl Canc Inst. 2022;34(1):21. doi: 10.1186/s43046-022-00123-6.
  19. NCCN Clinical Practice Guidelines in Oncology. Multiple Myeloma. Version 3.2023 (Internet). Available from: www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf (accessed 27.02.2023).
  20. Кострома И.И., Жернякова А.А., Чубукина Ж.В. и др. Заготовка гемопоэтических стволовых клеток у больных множественной миеломой: влияние предшествующей аутоТГСК терапии леналидомидом и режима мобилизации. Клиническая онкогематология. 2018;11(2):192–7. doi: 10.21320/2500-2139-2018-11-2-192-197.
    [Kostroma II, Zhernyakova AA, Chubukina ZhV, et al. Hematopoietic Stem Cell Collection in Multiple Myeloma Patients: Influence of the Lenalidomide-Based Therapy and Mobilization Regimen Prior to Auto-HSCT. Clinical oncohematology. 2018;11(2):192–7. doi: 10.21320/2500-2139-2018-11-2-192-197. (In Russ)]
  21. Кострома И.И., Жернякова А.А., Чубукина Ж.В. и др. Факторы, связанные с эффективной заготовкой и приживлением аутотрансплантата у пациентов с множественной миеломой. Клиническая онкогематология. 2019;12(1):32–6. doi: 10.21320/2500-2139-2019-12-1-32-36.
    [Kostroma II, Zhernyakova AA, Chubukina ZhV, et al. Factors Associated with Efficient Harvesting and Engraftment of Auto-Transplants in Multiple Myeloma Patients. Clinical oncohematology. 2019;12(1):32–6. doi: 10.21320/2500-2139-2019-12-1-32-36. (In Russ)]
  22. Auner H, Iacobelli S, Sbianchi G, et al. Melphalan 140 mg/m2 or 200 mg/m2 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(3):514–21. doi: 10.3324/haematol.2017.181339.
  23. Straka C, Salwender H, Knop S, et al. Full or intensity-reduced high-dose melphalan and single or double autologous stem cell transplant with or without bortezomib consolidation in patients with newly diagnosed multiple myeloma. Eur J Haematol. 2021;107(5):529–42. doi: 10.1111/ejh.13690.