Efekti daratumumab monoklonskog antitela u kombinaciji sa režimom lečenja zasnovanim na iksazomibu na preživljavanje obolelih od relapsnog/refraktornog multiplog mijeloma
Sažetak
Uvod/Cilj. Kombinovana terapija daratumumabom i iksazomibom je ranije korišćena za lečenje multiplog mijeloma (MM), ali rezultati lečenja ovim lekovima i bezbednost još uvek nisu potvrđeni. Cilj rada bio je da se procene efekti daratumumab monoklonskog antitela u kombinaciji sa režimom lečenja zasnovanim na iksazomibu na preživljavanje obolelih od relapsnog/refraktornog MM (RRMM). Metode. Retrospektivnom studijom obuhvaćeni su klinički podaci 65 obolelih od RRMM, primljenih u periodu od marta 2016. do marta 2019. godine. Bolesnici su podeljeni prema različitim režimima lečenja na dve grupe: na grupu A, koja je obuhvatila 31 bolesnika lečenih kombinacijom iksazomiba, deksametazona i lenalidomida i grupu B koja je obuhvatila 34 bolesnika lečenih kombinacijom iksazomiba, deksametazona, lenalidomida i daratumumaba. Upoređivani su ishodi lečenja, neželjene reakcije, kvalitet života i preživljavanje bolesnika. Rezultati. Nisu pokazane značajne razlike u objektivnoj stopi odgovora između grupa A i B (70,97% vs. 85,29%) niti u vrsti ili stepenu neželjenih reakcija (p = 0,161). Skorovi svih dimenzija Upitnika Svetske zdravstvene organizacije o kvalitetu života – kratka verzija (World Health Organization Quality of Life Brief Version) grupe B bili su viši od skorova grupe A posle lečenja (p < 0,05). Nije bilo značajne razlike u jednogodišnjoj i trogodišnjoj stopi preživljavanja između grupe A (64,52%, 19,35%) i grupe B (73,53%, 32,35%) (p = 0,432 i p = 0,234, redom). Ipak, grupa B imala je značajno višu stopu preživljavanja od grupe A (61,76% vs. 35,48%) (p = 0,034). Zaključak. Kombinacija daratumumaba i režima lečenja zasnovanog na iksazomibu poboljšava preživljavanje i kvalitet života obolelih od RRMM, bez povećanja stope incidencije neželjenih reakcija tokom lečenja.
Reference
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.