Effects of monoclonal antibody daratumumab combined with ixazomib-based treatment regimen on survival of patients with relapsed/refractory multiple myeloma
Abstract
Background/Aim. Combination therapy with daratumumab and ixazomib has been previously used for the treatment of multiple myeloma (MM), but treatment outcomes of these drugs and safety have not yet been confirmed. The aim of the study was to assess the effects of monoclonal antibody daratumumab in combination with an ixazomib-based treatment regimen on the survival of patients with relapsed/refractory MM (RRMM). Methods. A retrospective study included the clinical data of 65 RRMM patients admitted from March 2016 to March 2019. The patients were divided according to different treatment regimens into two groups: Group A, with 31 patients, treated with a combination of ixazomib, dexamethasone, lenalidomide, and Group B, with 34 patients, treated with a combination of ixazomib, dexamethasone, lenalidomide, and daratumumab. Treatment outcomes, adverse reactions, quality of life, and survival were compared. Results. Groups A and B showed no significant differences in the objective response rate (70.97% vs. 85.29%) or the type and grade of adverse reactions (p = 0.161). The scores of all dimensions of the World Health Organization Quality of Life Brief Version of group B were higher than those of group A after treatment (p < 0.05). There was no significant difference in the one-year or three-year survival rate between group A (64.52%, 19.35%) and group B (73.53%, 32.35%) (p = 0.432 and p = 0.234, respectively). Still, group B had a significantly higher two-year survival rate than that of group A (61.76% vs. 35.48%) (p = 0.034). Conclusion. The combination of daratumumab and ixazomib-based treatment regimen helps improve the survival and quality of life of RRMM patients without increasing the incidence rate of adverse reactions during treatment.
References
Zheng Z, Lin K. A comparison of the efficacy and safety of ix-azomib and lenalidomide combined with dexamethasone in the treatment of multiple myeloma. Am J Transl Res 2021; 13(5): 5248–55.
Hájek R, Minařík J, Straub J, Pour L, Jungova A, Berdeja JG, et al. Ixazomib-lenalidomide-dexamethasone in routine clinical practice: effectiveness in relapsed/refractory multiple myelo-ma. Future Oncol 2021; 17(19): 2499–512.
Takakuwa T, Yamamura R, Ohta K, Kaneko H, Imada K, Nakaya A, et al. Outcomes of ixazomib/lenalidomide/dexamethasone for multiple myeloma: A multicenter retrospective analysis. Eur J Haematol 2021; 106(4): 555–62.
Terpos E, Ramasamy K, Maouche N, Minarik J, Ntanasis-Stathopoulos I, Katodritou E, et al. Real-world effectiveness and safety of ixazomib-lenalidomide-dexamethasone in re-lapsed/refractory multiple myeloma. Ann Hematol 2020; 99(5): 1049–61.
Davies F, Rifkin R, Costello C, Morgan G, Usmani S, Abonour R, et al. Real-world comparative effectiveness of triplets contain-ing bortezomib (B), carfilzomib (C), daratumumab (D), or ix-azomib (I) in relapsed/refractory multiple myeloma (RRMM) in the US. Ann Hematol 2021; 100(9): 2325–37.
Boiten HJ, Buijze M, Zweegman S, Levin MD. Ixazomib Treat-ment of IgA Multiple Myeloma with Hyperviscosity Syn-drome. Clin Lymphoma Myeloma Leuk 2020; 20(11): e832–5.
Goldsmith SR, Foley N, Schroeder MA. Daratumumab for the treatment of multiple myeloma. Drugs Today (Barc) 2021; 57(10): 591–605.
Wang Q, Dong Z, Su J, Huang J, Xiao P, Tian L, et al. Ixazomib inhibits myeloma cell proliferation by targeting UBE2K. Bio-chem Biophys Res Commun 2021; 549: 1–7.
Tzogani K, Florez B, Markey G, Caleno M, Olimpieri OM, Melchi-orri D, et al. European Medicines Agency review of ixazomib (Ninlaro) for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. ESMO Open 2019; 4(5): e000570.
Dimopoulos MA, Špička I, Quach H, Oriol A, Hájek R, Garg M, et al. Ixazomib as Postinduction Maintenance for Patients With Newly Diagnosed Multiple Myeloma Not Undergoing Autologous Stem Cell Transplantation: The Phase III TOURMALINE-MM4 Trial. J Clin Oncol 2020; 38(34): 4030–41. Erratum in: J Clin Oncol 2022; 40(8): 919.
Offidani M, Corvatta L, Morè S, Nappi D, Martinelli G, Olivieri A, et al. Daratumumab for the Management of Newly Diag-nosed and Relapsed/Refractory Multiple Myeloma: Current and Emerging Treatments. Front Oncol 2021; 10: 624661.
Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and surviv-al. Cancer 1975; 36(3): 842–54.
Li J, Bao L, Xia Z, Wang S, Zhou X, Ding K, et al. Ixazomib-based frontline therapy in patients with newly diagnosed mul-tiple myeloma in real-life practice showed comparable efficacy and safety profile with those reported in clinical trial: a multi-center study. Ann Hematol 2020; 99(11): 2589–98.
Chen WM. The guidelines for the diagnosis and management of multiple myeloma in China (2017 revision): interpretation of treatment of relapsed/refractory multiple myeloma. Zhonghua Nei Ke Za Zhi 2017; 56(11): 799–800. (Chinese)
Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, et al. International Myeloma Working Group consensus crite-ria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 2016; 17(8): e328–46.
Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol 2020; 95(5): 548–67. Erratum in: Am J Hematol 2020; 95(11): 1444.
National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 [Internet]. U.S. De-partment of health and human services; 2017 [cited 2018 Nov 8; accessed 2025 Jan 13]. Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf
Kumar P, Sen RK, Aggarwal S, Jindal K, Rajnish RK. Assessment and reliability of the World Health Organisation quality of life (WHO QOL-BREF) questionnaire in total hip replacement patients. J Clin Orthop Trauma 2020; 11(Suppl 5): S756–9.
Stege CAM, Nasserinejad K, van der Spek E, Bilgin YM, Kentos A, Sohne M, et al. Ixazomib, Daratumumab, and Low-Dose Dex-amethasone in Frail Patients With Newly Diagnosed Multiple Myeloma: The Hovon 143 Study. J Clin Oncol 2021; 39(25): 2758–67.
Ziff M, Lawson G, De-Silva D, Cheesman S, Kyriakou C, Mahmood S, et al. Ixazomib with lenalidomide and dexame-thasone for patients with relapsed multiple myeloma: impact of 17p deletion and sensitivity to proteasome inhibitors from a real world data-set. Leuk Lymphoma 2021; 62(5): 1243–6.
Saltarella I, Desantis V, Melaccio A, Solimando AG, Lamanuzzi A, Ria R, et al. Mechanisms of Resistance to Anti-CD38 Daratumumab in Multiple Myeloma. Cells 2020; 9(1): 167.
Mateos MV, Nahi H, Legiec W, Grosicki S, Vorobyev V, Spicka I, et al. Subcutaneous versus intravenous daratumumab in pa-tients with relapsed or refractory multiple myeloma (CO-LUMBA): a multicentre, open-label, non-inferiority, random-ised, phase 3 trial. Lancet Haematol 2020; 7(5): e370–80. Er-ratum in: Lancet Haematol 2020; 7(10): e710.
Chong LL, Soon YY, Soekojo CY, Ooi M, Chng WJ, de Mel S. Daratumumab-based induction therapy for multiple myeloma: A systematic review and meta-analysis. Crit Rev Oncol Hema-tol 2021; 159: 103211.
Maouche N, Kishore B, Jenner MW, Boyd K, Bhatti Z, Bird SA, et al. Ixazomib, lenalidomide, and dexamethasone is effective and well tolerated in multiply relapsed (≥2nd relapse) refrac-tory myeloma: a multicenter real world UK experience. Leuk Lymphoma 2021; 62(6): 1396–404.