Comparative Efficacy of Autologous Hematopoietic Stem Cell Mobilization Regimens in Multiple Myeloma Patients
ISSN (print) 1997-6933     ISSN (online) 2500-2139
2024-1
PDF_2024-17-1_43-49 (Russian)

Keywords

multiple myeloma
mobilization regimens
autologous HSC collection

How to Cite

1.
Kostroma I.I., Chubukina Z.V., Yudina V.A., Romanenko N.A., Stepchenkova E.I., Bessmeltsev S.S., Sidorkevich S.V., Gritsaev S.V. Comparative Efficacy of Autologous Hematopoietic Stem Cell Mobilization Regimens in Multiple Myeloma Patients. Клиническая онкогематология. 2024;17(1):43-49. doi:10.21320/2500-2139-2024-17-1-43-49

Keywords

Abstract

Aim. To compare the efficacy of mobilization regimens (MR) differing in their composition and intensity, with the purpose of defining the criteria to personalize the choice of MR based on clinical and hematological characteristics of multiple myeloma (MM) patients.

Materials & Methods. A retrospective analysis of the autologous hematopoietic stem cell (HSC) mobilization and autograft harvesting results was performed in 177 patients with newly diagnosed MM. The patients were divided into 4 groups. Group 1 included 62 patients with the median age of 53 years who were treated with single injection of cyclophosphamide (CF) dose 3 g/m2 as MR. Group 2 consisted of 71 patients with the median age of 58 years who received vinorelbine 35 mg/m2. Granulocyte colony-stimulating factor (G-CSF) as a monoregimen was administered to group 3 consisting of 33 patients with the median age of 55 years. Group 4 included 11 patients with the median age of 57 years who received G-CSF enhanced by plerixafor administration. G-CSF 10 µg/kg was used as MR. In all chemomobilization cases, daily G-CSF 10 µg/kg started on Day 4 from the administration of the chemotherapy drug prescribed as MR.

Results. In the analyzed groups, the median time from MR start to the first leukocyte apheresis session was 11, 8, 5, and 5 days, respectively. On the first leukocyte apheresis day, the median CD34+ cell collection in group 3 was significantly lower than in groups 1, 2, and 4: 2.2 × 106/kg vs. 3.79 × 106/kg, 7.22 × 106/kg, and 3.9 × 106/kg, respectively. The total CD34+ cell collection after two leukocyte apheresis sessions was also the lowest in group 3 compared with groups 1, 2, and 4: 3.22 × 106/kg vs. 5.2 × 106/kg, 4.95 × 106/kg, and 7.5 × 106/kg, respectively. In the analyzed groups, the rate of mobilization with CD34+ cell collection < 2.0 × 106/kg was 6.5 %, 5.6 %, 18.2 %, and 9.1 %. The evaluation of the results in all patients showed a direct correlation of CD34+ cell collection with lenalidomide administered before autologous HSC mobilization. A significant difference in CD34+ cell collection in lenalidomide recipients vs. non-recipients was reported when vinorelbine as MR and G-CSF as monoregimen (р = 0.001 and р = 0.022, respectively) were used. No significant differences were observed either with CF or G-CSF combined with plerixafor treatment.

Conclusion. Based on the findings, age of a MM patient, comorbidities, and prior lenalidomide administration can be regarded as key criteria for choosing one of 4 MRs.

PDF_2024-17-1_43-49 (Russian)

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. Клинические рекомендации. Множественная миелома. 2020 (электронный документ). Доступно по: www.oncology-association.ru/mnozhestvennaja_myeloma.pdf. Ссылка активна на 05.07.2023. [Clinical guidelines. Multiple myeloma. 2020 (Internet). Available from: www.oncology-association.ru/mnozhestvennaja_myeloma.pdf. Accessed 05.07.2023. (In Russ)]
  3. Kumar S, Dispenzieri A, Lacy M, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28(5):1122–8. doi: 10.1038/leu.2013.313.
  4. Fermand J, Katsahian S, Divine M, et al. High dose therapy and autologous blood stem cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: long-term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol. 2005;23(36):9227–33. doi: 10.1200/JCO.2005.03.0551.
  5. Mina R, Petrucci M, Corradini P, et al. Treatment intensification with autologous stem cell transplantation and lenalidomide maintenance improves survival outcomes of patients with newly diagnosed multiple myeloma in complete response. Clin Lymphoma Myeloma Leuk. 2018;18(8):533–40. doi: 10.1016/j.clml.2018.05.019.
  6. Mohan M, Kendrick S, Szabo A, et al. Clinical implications of loss of bone marrow minimal residual disease negativity in multiple myeloma. Blood Adv. 2021;6(3):808–17. doi: 10.1182/bloodadvances.2021005822.
  7. Кострома И.И., Жернякова А.А., Грицаев С.В. Отдельные аспекты заготовка аутотрансплантата у больных множественной миеломой. Вопросы онкологии. 2019;65(4):504–9. [Kostroma II, Zhernyakova AA, Gritsaev SV. Some aspects of autotransplant collection in patients with multiple myeloma. Voprosy onkologii. 2019;65(4):504–9. (In Russ)]
  8. Cowan A, Stevenson P, Green D, et al. Prolonged lenalidomide therapy does not impact autologous peripheral blood stem cell mobilization and collection in multiple myeloma patients: a single-center retrospective analysis. Transplant Cell Ther. 2021;27(8):661.e1–661.e6. doi: 10.1016/j.jtct.2021.04.010.
  9. Грицаев С.В., Кузяева А.А., Бессмельцев С.С. Отдельные аспекты аутологичной трансплантации гемопоэтических стволовых клеток при множественной миеломе. Клиническая онкогематология. 2017;10(1):7–12. doi: 10.21320/2500-2139-2017-10-1-7-12. [Gritsaev SV, Kuzyaeva AA, Bessmel’tsev SS. Certain Aspects of Autologous Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma. Clinical oncohematology. 2017;10(1):7–12. doi: 10.21320/2500-2139-2017-10-1-7-12. (In Russ)]
  10. Грицаев С.В., Кузяева А.А., Кострома И.И. и др. Первый опыт мобилизации гемопоэтических стволовых клеток в периферическую кровь винорелбином у больных лимфопролиферативными заболеваниями. Медицина экстремальных ситуаций. 2017;4:30–5. [Gritsaev SV, Kuzyaeva AA, Kostroma II, et al. A first step in mobilization of hematopoietic stem cells into peripheral blood by vinorelbine in patients with lymphoproliferative diseases. Meditsina ekstremalnykh situatsii. 2017;4:30–5. (In Russ)]
  11. Грицаев С.В., Кострома И.И., Чубукина Ж.В. и др. Сравнительная эффективность винорелбина и циклофосфана в режиме мобилизации для заготовки аутотрансплантата. Medline.ru. 2017;18:409–24. [Gritsaev SV, Kostroma II, Chubukina ZhV, et al. Comparative effectiveness of vinorelbine and cyclophosphan as mobilization regimen for autotransplant harvesting. Medline.ru. 2017;18:409–24. (In Russ)]
  12. Кострома И.И., Юдина В.А., Сабитова Р.Р. и др. Эффективность трансплантации аутологичных гемопоэтических стволовых клеток у больных множественной миеломой старше 60 лет. Клиническая онкогематология. 2023;16(3):287–93. doi: 10.21320/2500-2139-2023-16-3-287-293. [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. doi: 10.21320/2500-2139-2023-16-3-287-293. (In Russ)]
  13. 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.
  14. 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.
  15. 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)]
  16. Kumar S, Dispenzieri A, Lacy M, et al. Impact of lenalidomide therapy on stem cell mobilization and engraftment post-peripheral blood stem cell transplantation in patients with newly diagnosed myeloma. Leukemia. 2007;21(9):2035–42. doi: 10.1038/sj.leu.2404801.
  17. Paripati H, Stewart A, Cabou S, et al. Compromised stem cell mobilization following induction therapy with lenalidomide in myeloma. Leukemia. 2008;22(6):1282–4. doi: 10.1038/sj.leu.2405100.
  18. Bhutani D, Zonder J, Valent J, et al. Evaluating the effects of lenalidomide induction therapy on peripheral stem cells collection in patients undergoing autologous stem cell transplant for multiple myeloma. Support Care Cancer. 2013;21(9):2437–42. doi: 10.1007/s00520-013-1808-5.
  19. Popat U, Saliba R, Thandi R, et al. Impairment of filgrastim-induced stem cell mobilization after prior lenalidomide in patients with multiple myeloma. Biol Blood Marrow Transplant. 2009;15(6):718–23. doi: 10.1016/j.bbmt.2009.02.011.
  20. Moreau P, Attal M, Hulin C, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019;394(10192):29–38. doi: 10.1016/S0140-6736(19)31240-1.
  21. Voorhees P, Kaufman J, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136(8):936–45. doi: 10.1182/blood.2020005288.
  22. Mishra K, Jandial A, Sandal R, et al. Poor mobilisation after daratumumab based combination chemotherapy in patients of newly diagnosed multiple myeloma. Indian J Hematol Blood Transfus. 2019;35(3):584–6. doi: 10.1007/s12288-019-01135-4.
  23. Weaver C, Hazelton B, Birch R, et al. An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myeloablative chemotherapy. Blood. 1995;86(10):3961–9.
  24. Luo C, Wu G, Huang X, et al. Efficacy of hematopoietic stem cell mobilization regimens in patients with hematological malignancies: a systematic review and network meta-analysis of randomized controlled trials. Stem Cell Res Ther. 2022;13(1):123. doi: 10.1186/s13287-022-02802-6.
  25. Chen K, Bucci T, Shaw J, et al. Plerixafor strategies for autologous hematopoietic cell transplant mobilization: A comparison of efficacy and cost. Transfus Apher Sci. 2022;61(2):103303. doi: 10.1016/j.transci.2021.
  26. Passos R, Feldens T, Marcolino M, et al. Economic evaluation of plerixafor addition in the mobilization and leukapheresis of hematopoietic stem cells for autologous transplantation: a systematic review. Expert Rev Pharmacoecon Outcomes Res. 2023;23(1):15–28. doi: 10.1080/14737167.2023.2140140.
  27. Lazzaro C, Castagna L, Lanza F, et al. Chemotherapy-based versus chemotherapy-free stem cell mobilization (± plerixafor) in multiple myeloma patients: an Italian cost-effectiveness analysis. Bone Marrow Transplant. 2021;56(8):1876–87. doi: 10.1038/s41409-021-01251-8.
  28. Rybinski B, Rapoport A, Badros A, et al. Prolonged lenalidomide induction does not significantly impair stem cell collection in multiple myeloma patients mobilized with cyclophosphamide or plerixafor: a report from the Covid era. Clin Lymphoma Myeloma Leuk. 2022;22(8):е716–e729. doi: 10.1016/j.clml.2022.03.013.
  29. Dhakal B, Zhang M, Burns L, et al. Efficacy, safety, and cost of mobilization strategies in multiple myeloma: A prospective observational study. Haematologica. 2023;108(8):2249–54. 10.3324/haematol.2022.282269.
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Copyright (c) 2023 Clinical Oncohematology