Vol 12, No 1 (2021)
Case report
Published online: 2021-04-07
Effectiveness and safety of ixazomib–lenalidomide–dexamethasone in high-cytogenetic-risk relapsed/refractory multiple myeloma — results of the Polish Myeloma Group observational study
DOI: 10.5603/HCP.2021.0002
Hematology in Clinical Practice 2021;12(1):8-17.
Abstract
The survival of patients with multiple myeloma (MM) has significantly improved in recent years due to the introduction of new drugs such as proteasome inhibitors (PI) or immunomodulatory drugs (ImiDs). However, MM is still an incurable condition, with very variable clinical course.
The group of patients with especially poor prognosis are individuals with relapsed/refractory multiple myeloma (RRMM) with specific cytogenetic disorders — del(17p), t(4;14), t(14;16). Among the therapies that are currently in use the ixazomib–lenalidomid–dexamethasone (IRd) is considered as a candidate to improve outcome.
In this study, we analyzed the cases of patients diagnosed with high-risk molecular RRMM, who have been treated with the IRd chemotherapy regimen. An aggressive case report with no known cytogenetic data was also added. The data was collected from four centers in Poland as part of the Polish Myeloma Group observational study.
The results suggest high efficacy and good safety profile of IRd therapy in patients with RRMM and unfavorable cytogenetics.
Keywords: ixazomiblenalidomidehigh riskcytogeneticrelapsed/refractory multiple myeloma
References
- Multiple myeloma: 2018 update on diagnosis, risk‐stratification, and management. Am J Hematol. 2018; 93(8): 981–1114.
- Kazmi SM, Nusrat M, Gunaydin H, et al. Outcomes among high-risk and standard-risk multiple myeloma patients treated with high-dose chemotherapy and autologous hematopoietic stem-cell transplantation. Clin Lymphoma Myeloma Leuk. 2015; 15(11): 687–693.
- Mikhael JR, Dingli D, Roy V, et al. Mayo Clinic. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013. Mayo Clin Proc. 2013; 88(4): 360–376.
- Sonneveld P, Avet-Loiseau H, Lonial S, et al. Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood. 2016; 127(24): 2955–2962.
- Fonseca R, Bergsagel PL, Drach J, et al. International Myeloma Working Group. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009; 23(12): 2210–2221.
- Kuiper R, van Duin M, van Vliet MH, et al. Prediction of high- and low-risk multiple myeloma based on gene expression and the International Staging System. Blood. 2015; 126(17): 1996–2004.
- Gupta N, Hanley MJ, Xia C, et al. Clinical pharmacology of ixazomib: the first oral proteasome inhibitor. Clin Pharmacokinet. 2019; 58(4): 431–449.
- Mateos MV, Masszi T, Grzasko N, et al. TOURMALINE-MM1 Study Group. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016; 374(17): 1621–1634.
- Moreau P, San Miguel J, Sonneveld P, et al. ESMO Guidelines Committee. Multiple myeloma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017; 28(Suppl_4): iv52–iv61.
- Charliński G. Leczenie nawrotowego/opornego szpiczaka plazmocytowego w Polsce w oparciu o program lekowy Ministerstwa Zdrowia w nawiązaniu do zaleceń Europejskiego Towarzystwa Onkologii Klinicznej. Hematologia. 2020; 11(1): 21–28.
- Palumbo A, Avet-Loiseau H, Oliva S, et al. Revised International Staging System for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol. 2015; 33(26): 2863–2869.
- Avet-Loiseau H, Hulin C, Campion L, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood. 2007; 109(8): 3489–3495.
- Lancman G, Tremblay D, Barley K, et al. The effect of novel therapies in high-molecular-risk multiple myeloma. Clin Adv Hematol Oncol. 2017; 15(11): 870–879.
- Qureshi N, Vogel S, Way CV, et al. The proteasome: a central regulator of inflammation and macrophage function. Immunol Res. 2005; 31(3): 243–260.
- Charakterystyka Produktu Leczniczego Ninlaro. https://www.ema.europa.eu/en/documents/product-information/ninlaro-epar-product-information_pl.pdf (December 31, 2020).
- Ito S. Proteasome inhibitors for the treatment of multiple myeloma. Cancers (Basel). 2020; 12(2): 265.
- Avet-Loiseau H, Bahlis NJ, Chng WJ, et al. Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients. Blood. 2017; 130(24): 2610–2618.
- Giannopoulos K, Jamroziak K, Usnarska-Zubkiewicz L, et al. Zalecenia Polskiej Grupy Szpiczakowej dotyczące rozpoznawania i leczenia szpiczaka plazmocytowego oraz innych dyskrazji plazmocytowych na rok 2018/2019. Acta Haematol Pol. 2018; 49(4): 157–206.
- Kumar SK, Callander NS, Hillengass J, et al. NCCN guidelines insights: multiple myeloma, version 1.2020. J Natl Compr Canc Netw. 2019; 17(10): 1154–1165.
- Hou J, Jin J, Xu Y, et al. Randomized, double-blind, placebo-controlled phase III study of ixazomib plus lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma: China Continuation study. J Hematol Oncol. 2017; 10(1): 137.
- Stewart AK, Rajkumar SV, Dimopoulos MA, et al. ASPIRE Investigators. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015; 372(2): 142–152.
- Dimopoulos MA, Moreau P, Palumbo A, et al. ENDEAVOR Investigators. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016; 17(1): 27–38.
- Giannopoulos K, Jędrzejczak W, Jamroziak K, et al. Iksazomib u chorych z nawrotowym lub opornym na leczenie szpiczakiem plazmocytowym. Acta Haematol Pol. 2017; 48(3): 160–164.
- Morgan GJ, Walker BA, Davies FE. The genetic architecture of multiple myeloma. Nat Rev Cancer. 2012; 12(5): 335–348.
- Tzogani K, Florez B, Markey G, 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.
