Isatuximab-containing regimens for the treatment of patients with newly diagnosed multiple myeloma: A literature review and a clinical case

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Multiple myeloma (MM) is a malignant clonal lymphoproliferative disease. Over the past few decades, there has been a breakthrough in the treatment of MM due to the introduction of high-dose therapies and innovative biological agents. Currently, approaches to therapy of both candidates and non-candidates for autologous hematopoietic stem cell transplantation (auto-HSCT) are still evolving. Isatuximab is an immunoglobulin (Ig)Gk monoclonal antibody to CD38 that has anti-tumor activity through several mechanisms of action. The effectiveness of adding isatuximab to three-component regimens in patients with MM was studied in several randomized studies. Publications on the use of isatuximab-containing MM induction therapy regimens were reviewed. The authors’ experience of using the Isa-VRd regimen in a patient with MM who is not a candidate for auto-HSCT is presented. The patient, 72 years old, was admitted to the National Medical Research Center for Hematology in September 2024 with suspected paraproteinemic hemoblastosis. The disease onset was acute; azotemia signs appeared in August 2024. A full range of laboratory and instrumental examinations diagnosed symptomatic MM with acute renal injury. Due to the advanced age and comorbidities, the patient was not considered a candidate for high-dose chemotherapy with auto-HSCT. The patient was initiated with four-component therapy according to the Isa-VRd regimen. After the first course, a very good partial remission and a partial renal response were achieved. Treatment continued; currently, the patient is receiving the third course.

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Maiia Soloveva

National Medical Research Center for Hematology

编辑信件的主要联系方式.
Email: solomaiia@yandex.ru
ORCID iD: 0000-0003-4142-171X

Cand. Sci. (Med.)

俄罗斯联邦, Moscow

Maxim Solovev

National Medical Research Center for Hematology

Email: solomaiia@yandex.ru
ORCID iD: 0000-0002-7944-6202

Cand. Sci. (Med.)

俄罗斯联邦, Moscow

Alla Kovrigina

National Medical Research Center for Hematology

Email: solomaiia@yandex.ru
ORCID iD: 0000-0002-1082-8659

D. Sci. (Biol.)

俄罗斯联邦, Moscow

Larisa Mendeleeva

National Medical Research Center for Hematology

Email: solomaiia@yandex.ru
ORCID iD: 0000-0002-4966-8146

D. Sci. (Med.)

俄罗斯联邦, Moscow

参考

  1. Raab MS, Podar K, Breitkreutz I, et al. Multiple myeloma. Lancet. 2009;374(9686):324-9. doi: 10.1016/S0140-6736(09)60221-X
  2. Padala SA, Barsouk A, Barsouk A, et al. Epidemiology, Staging, and Management of Multiple Myeloma. Med Sci (Basel). 2021;9(1):3. doi: 10.3390/medsci9010003
  3. Kanas G, Clark O, Keeven K, et al. Estimate of multiple myeloma patients by line of therapy in the USA: population-level projections 2020-2025. Future Oncol. 2021;17(8):921-30. doi: 10.2217/fon-2020-0970
  4. Dimopoulos MA, 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
  5. Martin TG, Corzo K, Chiron M, et al. Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab. Cells. 2019;8(12):1522. doi: 10.3390/cells8121522
  6. Facon T, Dimopoulos MA, Leleu XP, et al. Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2024;391(17):1597-609. doi: 10.1056/NEJMoa2400712
  7. Ebraheem MS, Chakraborty R, Rochwerg B, et al. Quadruplet regimens for patients with newly diagnosed multiple myeloma: a systematic review and meta-analysis. Blood Adv. 2024;8(23):5993-6002. doi: 10.1182/bloodadvances.2024014139
  8. Leypoldt LB, Tichy D, Besemer B, et al. Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone for the Treatment of High-Risk Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2024;42(1):26-37. doi: 10.1200/JCO.23.01696
  9. Leleu X, Hulin C, Lambert J, et al. Isatuximab, lenalidomide, dexamethasone and bortezomib in transplant-ineligible multiple myeloma: the randomized phase 3 BENEFIT trial. Nat Med. 2024;30(8):2235-21. doi: 10.1038/s41591-024-03050-2
  10. Facon T, Kumar SK, Plesner T, et al. Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(11):1582-56. doi: 10.1016/S1470-2045(21)00466-6
  11. San-Miguel J, Avet-Loiseau H, Paiva B, et al. Sustained minimal residual disease negativity in newly diagnosed multiple myeloma and the impact of daratumumab in MAIA and ALCYONE. Blood. 2022;139(4):492-501. doi: 10.1182/blood.2020010439

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2. Fig. 1. Histological examination of bone marrow trepan-biopsy material in the patient with MM. Hematoxylin and eosin staining. Among the myelopoiesis cells, an increased number of mature plasma cells are observed.

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3. Fig. 2. Immunohistochemical examination of bone marrow trepan-biopsy material in the patient with MM. Plasma cells, monotypic for the λ chain (single kappa + cells are dispersed in the interstitium), make up to ~13% of hematopoietic tissue when counted in “hot spots” at a magnification of 400.

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