Ixazomib – lenalidomide – dexamethason in heavily pretreated multiple myeloma patients – case reports

Česká verzia

Authors: M. Štork
Authors place of work: Interní hematologická a onkologická klinika LF MU a FN Brno
Published in the journal: Klin Onkol 2023; 36(2): 150-154
Category: Case Report
doi: https://doi.org/10.48095/ccko2023150

Summary

Background: The treatment of aggressive multiple myeloma (MM) patients, resistant to several treatment modalities, is very difficult in the real-world-evidence conditions. Ixazomib is a second-generation oral proteasome inhibitor. In combination with lenalidomide and dexamethasone, it is an effective and low-toxic treatment regimen for patients with relapsed or refractory MM. Observation: The presented case reports of two patients with an aggressive course of MM demonstrate the surprising effectiveness of this regimen. Conclusion: Repeated treatment with a combination of proteasome inhibitors (ixazomib) and immunomodulatory drugs (lenalidomide) may lead to significant clinical benefit in some patients and should be considered even in end-stage disease patients.

Keywords:

Multiple myeloma – plasmacytoma – leukemia – ixazomib – retreatment

Zdroje

1. Maluskova D, Svobodová I, Kucerova M et al. Epidemiology of multiple myeloma in the Czech Republic. Klin Onkol 2017; 30 (Supplementum2): 35–42. doi: 10.14735/amko20172S35.

2. Rajkumar SV. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. Am J Hematol 2022; 97 (8): 1086–1107. doi: 10.1002/ajh.26590.

3. Sevcikova S, Minarik J, Stork M et al. Extramedullary disease in multiple myeloma – controversies and future directions. Blood Rev 2019; 36: 32–39. doi: 10.1016/j.blre.2019.04.002.

4. Bahlis NJ, Dimopoulos MA, White DJ et al. Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study. Leukemia 2020; 34 (7): 1875–1884. doi: 10.1038/s41375-020-0711-6.

5. Avet-Loiseau H, San-Miguel J, Casneuf T et al. Evaluation of sustained minimal residual disease negativity with daratumumab-combination regimens in relapsed and/or refractory multiple myeloma: analysis of POLLUX and CASTOR. J Clin Oncol 2021; 39 (10): 1139–1149. doi: 10.1200/JCO.20.01814.

6. Facon T, Kumar S, Plesner T et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med 2019; 380 (22): 2104–2115. doi: 10.1056/NEJMoa1817249.

7. Stewart AK, Rajkumar SV, Dimopoulos MA et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med 2015; 372 (2): 142–152. doi: 10.1056/NEJMoa1411321.

8. Richardson PG, Oriol A, Beksac M et al. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial. Lancet Oncol 2019; 20 (6): 781–794. doi: 10.1016/S1470-2045 (19) 30152-4.

9. San Miguel JF, Schlag R, Khuageva NK et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 2008; 359 (9): 906–917. doi: 10.1056/NEJMoa0801479.

10. Argyriou AA, Iconomou G, Kalofonos HP. Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature. Blood 2008; 112 (5): 1593–1599. doi: 10.1182/blood-2008-04-149385.

11. Moreau P, Mateos MV, Berenson JR et al. Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study. Lancet Oncol 2018; 19 (7): 953–964. doi: 10.1016/S1470-2045 (18) 30354-1.

12. Gay F, Musto P, Rota-Scalabrini D et al. Carfilzomib with cyclophosphamide and dexamethasone or lenalidomide and dexamethasone plus autologous transplantation or carfilzomib plus lenalidomide and dexamethasone, followed by maintenance with carfilzomib plus lenalidomide or lenalidomide alone for patients with newly diagnosed multiple myeloma (FORTE): a randomised, open-label, phase 2 trial. Lancet Oncol 2021; 22 (12): 1705–1720. doi: 10.1016/S1470-2045 (21) 00535-0.

13. Moreau P, Masszi T, Grzasko N et al. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med 2016; 374 (17): 1621–1634. doi: 10.1056/NEJMoa1516282.

14. Richardson PG, Kumar SK, Masszi T et al. Final overall survival analysis of the TOURMALINE-MM1 Phase III trial of ixazomib, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma. J Clin Oncol 2021; 39 (22): 2430–2442. doi: 10.1200/JCO.21.00972.

15. Cohen YC, Magen H, Lavi N et al. Ixazomib-based regimens for relapsed/refractory multiple myeloma: are real-world data compatible with clinical trial outcomes? A multi-site Israeli registry study. Ann Hematol 2020; 99 (6): 1273–1281. doi: 10.1007/s00277-020-03985-9.

16. Minarik J, Pika T, Radocha J et al. Survival benefit of ixazomib, lenalidomide and dexamethasone (IRD) over lenalidomide and dexamethasone (Rd) in relapsed and refractory multiple myeloma patients in routine clinical practice. BMC Cancer 2021; 21 (1): 73.

17. Hájek R, Minařík J, Straub J et al. Ixazomib-lenalidomide-dexamethasone in routine clinical practice: effectiveness in relapsed/refractory multiple myeloma. Future Oncol 2021; 17 (19): 2499–2512. doi: 10.1186/s12885-020-07732-1.

18. Minarik J, Radocha J, Jungova A et al. Ixazomib, lenalidomide and dexamethasone in relapsed and refractory multiple myeloma in routine clinical practice: extended follow-up analysis and the results of subsequent therapy. Cancers (Basel) 2022; 14 (20): 5165. doi: 10.3390/cancers14205165.

19. Costa LJ, Hungria V, Mohty M et al. How I treat triple-class refractory multiple myeloma. Br J Haematol. 2022; 198 (2): 244–256. doi: 10.1111/bjh.18185.

20. Jagannath S, Lin Y, Goldschmidt H et al. KarMMa-RW: comparison of idecabtagene vicleucel with real-world outcomes in relapsed and refractory multiple myeloma. Blood Cancer J 2021; 11: 116. doi: 10.1038/s41408-021-00507-2.

21. Moreau P, Garfall AL, van de Donk NWCJ et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med 2022; 387 (6): 495–505. doi: 10.1056/NEJMc2211969.

22. Chari A, Minnema MC, Berdeja JG et al. Talquetamab, a T-cell-redirecting GPRC5D bispecific antibody for multiple myeloma. N Engl J Med 2022; 387 (24): 2232–2244. doi: 10.1056/NEJMoa2204591.

23. van de Donk NWCJ, Usmani SZ, Yong K. CAR T-cell therapy for multiple myeloma: state of the art and prospects. Lancet Haematol 2021; 8 (6): e446–e461. doi: 10.1016/S2352-3026 (21) 00057-0.

24. Chari A, Romanus D, Palumbo A et al. Randomized clinical trial representativeness and outcomes in real-world patients: comparison of 6 hallmark randomized clinical trials of relapsed/refractory multiple myeloma. Clin Lymphoma Myeloma Leuk 2020; 20 (1): 8–17. doi: 10.1016/j.clml.2019.09.625.

25. Lemieux C, Johnston LJ, Lowsky R et al. Outcomes with autologous or allogeneic stem cell transplantation in patients with plasma cell leukemia in the era of novel agents. Biol Blood Marrow Transplant 2020; 26 (12): e328–e332. doi: 10.1016/j.bbmt.2020.08.035.

26. Attal M, Lauwers-Cances V, Hulin C et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med 2017; 376 (14): 1311–1320. doi: 10.1056/NEJMoa1611750.

27. Tacchetti P, Pantani L, Patriarca F et al. Bortezomib, thalidomide, and dexamethasone followed by double autologous haematopoietic stem-cell transplantation for newly diagnosed multiple myeloma (GIMEMA-MMY-3006): long-term follow-up analysis of a randomised phase 3, open-label study. Lancet Haematol 2020; 7 (12): e861–e873. doi: 10.1016/S2352-3026 (20) 30323-9.

28. Durie BGM, Hoering A, Abidi MH et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet 2017; 389 (10068): 519–527. doi: 10.1016/S0140-6736 (16) 31594-X.

29. Palumbo A, Chanan-Khan A, Weisel K et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med 2016; 375 (8): 754–766. doi: 10.1182/blood.2020005288.

30. Jurczyszyn A, Waszczuk-Gajda A, Castillo JJ et al. Primary refractory multiple myeloma: a real-world experience with 85 cases. Leuk Lymphoma 2020; 61 (12): 2868–2875. doi: 10.1080/10428194.2020.1788014.

31. Ntanasis-Stathopoulos I, Gavriatopoulou M, Kastritis E et al. Multiple myeloma: role of autologous transplantation. Cancer Treat Rev 2020; 82: 101929. doi: 10.1016/ j.ctrv.2019.101929.

32. Attal M, Harousseau JL, Stoppa AM et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. NEJM 1996; 335 (2): 91–97. doi: 10.1056/NEJM199607113350204.

33. Hulin C, de la Rubia J, Dimopoulos MA et al. Bortezomib retreatment for relapsed and refractory multiple myeloma in real-world clinical practice. Health Sci Rep 2018; 2 (1): e104. doi: 10.1002/hsr2.104.

34. Stork M, Sevcikova S, Adam Z et al. Retreatment with lenalidomide is an effective option in heavily pretreated refractory multiple myeloma patients. Neoplasma 2018; 65 (4): 585–591. doi: 10.4149/neo_2018_170519N 363.

35. Corre J, Cleynen A, Robiou du Pont S et al. Multiple myeloma clonal evolution in homogeneously treated patients. Leukemia 2018; 32 (12): 2636–2647. doi: 10.1038/s41375-018-0153-6.

36. Garcés JJ, Bretones G, Burgos L et al. Circulating tumor cells for comprehensive and multiregional non-invasive genetic characterization of multiple myeloma. Leukemia 2020; 34 (11): 3007–3018. doi: 10.1038/s41375-020-0883-0.

37. Pour L, Sevcikova S, Greslikova H et al. Soft-tissue extramedullary multiple myeloma prognosis is significantly worse in comparison to bone-related extramedullary relapse. Haematologica 2014; 99 (2): 360–364. doi: 10.3324/haematol.2013.094409.

38. Stork M, Sevcikova S, Minarik J et al. Identification of patients at high risk of secondary extramedullary multiple myeloma development. British Journal of Haematology 2022; 196 (4): 954–962. doi: 10.1111/bjh.17925.

39. Nowakowski GS, Witzig TE, Dingli D et al. Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma. Blood 2005; 106 (7): 2276–2279. doi: 10.1182/blood-2005-05-1858.

40. Bezdekova R, Jelinek T, Kralova R et al. Necessity of flow cytometry assessment of circulating plasma cells and its connection with clinical characteristics of primary and secondary plasma cell leukaemia. British Journal of Haematology 2021; 195 (1): 95–107. doi: 10.1111/bjh.17713.

41. Kostopoulos IV, Stathopoulos IN, Rousakis P et al. Circulating plasma cells in newly diagnosed multiple myeloma: prognostic and more. J Clin Oncol 2023; 41 (3): 708–710. doi: 10.1200/JCO.22.01606.

42. Fernández de Larrea C, Kyle R, Rosiñol L et al. Primary plasma cell leukemia: consensus definition by the International Myeloma Working Group according to peripheral blood plasma cell percentage. Blood Cancer J 2021; 11 (12): 192. doi: 10.1038/s41408-021-00587-0.