BACKGROUND: We have performed a head to head comparison of all-oral triplet combination of ixazomib, lenalidomide and dexamethasone (IRD) versus lenalidomide and dexamethasone (RD) in patients with relapsed and refractory multiple myeloma (RRMM) in the routine clinical practice. METHODS: A total of 344 patients treated with IRD (N = 127) or RD (N = 217) were selected for analysis from the Czech Registry of Monoclonal Gammopathies (RMG). Descriptive statistics were used to assess patient's characteristics associated with the respective therapy. The primary endpoint was progression free survival (PFS), secondary end points included response rates and overall survival (OS). Survival endpoints were plotted using Kaplan-Meier methodology at 95% Greenwood confidence interval. Univariable and multivariable Cox proportional hazards models were used to evaluate the effect of treatment regimens and the significance of uneven variables. Statistical tests were performed at significance level 0.05. RESULTS: In the whole cohort, median PFS for IRD was 17.5 and for RD was 11.5 months favoring the all-oral triplet, p = 0.005; in patients within relapse 1-3, the median PFS was 23.1 vs 11.6 months, p = 0.001. The hazard ratio for PFS was 0.67 (95% confidence interval [CI] 0.51-0.89, p = 0.006). The PFS advantage translated into improved OS for patients treated with IRD, median 36.6 months vs 26.0 months (p = 0.008). The overall response rate (ORR) was 73.0% in the IRD group vs 66.2% in the RD group with a complete response rate (CR) of 11.1% vs 8.8%, and very good partial response (VGPR) 22.2% vs 13.9%, IRD vs RD respectively. The IRD regimen was most beneficial in patients ≤75 years with ISS I, II, and in the first and second relapse. Patients with the presence of extramedullary disease did not benefit from IRD treatment (median PFS 6.5 months). Both regimens were well tolerated, and the incidence of total as well as grade 3/4 toxicities was comparable. CONCLUSIONS: Our analysis confirms the results of the TOURMALINE-MM1 study and shows benefit of all-oral triplet IRD treatment versus RD doublet. It demonstrates that the addition of ixazomib to RD improves key survival endpoints in patients with RRMM in a routine clinical setting.

1st Department of Medicine 1st Faculty of Medicine Charles University and General Hospital Prague Prague Czech Republic

1st Medical Department Clinical Department of Haematology 1st Faculty of Medicine and General Teaching Hospital Charles University Prague Czech Republic

4th Department of Internal Medicine Hematology Faculty Hospital and Charles University in Hradec Kralove Hradec Kralove Czech Republic

Department of Clinical Hematology Hospital Ceske Budejovice Ceske Budejovice Czech Republic

Department of Clinical Hematology Regional Health Corporation Masaryk Hospital in Usti nad Labem Usti nad Labem Czech Republic

Department of Hemato Oncology Faculty of Medicine and Dentistry Palacky University Olomouc and University Hospital Olomouc Olomouc Czech Republic

Department of Hematology and Transfusiology Faculty of Medicine University Hospital Bratislava Bratislava Slovakia

Department of Hematology and Transfusion Medicine Hospital Pelhrimov Pelhrimov Czech Republic

Department of Hematology Hospital Liberec Liberec Czech Republic

Department of Hematology Silesian Hospital in Opava Opava Czech Republic

Department of Hematooncology University Hospital Ostrava and Faculty of Medicine University of Ostrava Ostrava Czech Republic

Department of Internal Medicine and Hematology 3rd Faculty of Medicine Charles University and Faculty Hospital Kralovske Vinohrady Prague Czech Republic

Department of Internal Medicine Hematology and Oncology University Hospital Brno and Faculty of Medicine Masaryk University Brno Czech Republic

Hematology and Oncology Department Charles University Hospital Pilsen Pilsen Czech Republic

Institute of Biostatistics and Analyses Ltd Brno Czech Republic

Millennium Pharmaceuticals Inc a wholly owned subsidiary of Takeda Pharmaceutical Company Limited Cambridge MA USA

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