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Comparative Study
. 2021 Jan 15;21(1):73.
doi: 10.1186/s12885-020-07732-1.

Survival benefit of ixazomib, lenalidomide and dexamethasone (IRD) over lenalidomide and dexamethasone (Rd) in relapsed and refractory multiple myeloma patients in routine clinical practice

Jiri Minarik  1 , Tomas Pika  2 , Jakub Radocha  3 , Alexandra Jungova  4 , Jan Straub  5 , Tomas Jelinek  6 , Ludek Pour  7 , Petr Pavlicek  8 , Martin Mistrik  9 , Lucie Brozova  10 , Petra Krhovska  2 , Katerina Machalkova  3 , Pavel Jindra  4 , Ivan Spicka  5 , Hana Plonkova  6 , Martin Stork  7 , Jaroslav Bacovsky  2 , Lenka Capkova  10 , Michal Sykora  11 , Petr Kessler  12 , Lukas Stejskal  13 , Adriana Heindorfer  14 , Jana Ullrychova  15 , Tomas Skacel  16   17 , Vladimir Maisnar  3 , Roman Hajek  6
Affiliations
Comparative Study

Survival benefit of ixazomib, lenalidomide and dexamethasone (IRD) over lenalidomide and dexamethasone (Rd) in relapsed and refractory multiple myeloma patients in routine clinical practice

Jiri Minarik et al. BMC Cancer. .

Abstract

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.

Keywords: Clinical trial; Dexamethasone; Ixazomib; Lenalidomide; Multiple myeloma; Patient registry.

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Conflict of interest statement

JM received honoraria from Amgen, Takeda, Celgene, Janssen, BMS. JR received honoraria from Amgen and MSD. TJ received personal fees from: Amgen, Takeda, Celgene, Janssen, Karyopharm. IS received honoraria from Celgene, Amgen, Janssen-Cilag, Takeda, BMS, Novartis, Sanofi, VM had consultancy and received honoraria from Janssen, Amgen, Celgene, Takeda, participated on advisory boards: Janssen, Amgen, Celgene, BMS, Takeda, JS received honoraria from Celgene, Amgen, Takeda, Jannsen, BMS.LC and LB declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Progression free survival from treatment initiation
Fig. 2
Fig. 2
Overall survival from treatment initiation
Fig. 3
Fig. 3
Subgroup analysis – association of IRD and RD with PFS
Fig. 4
Fig. 4
Progression free survival (a) and overall survival (b) by previous autologous stem cell transplantation (ASCT)
Fig. 5
Fig. 5
Progression free survival (a) and overall survival (b) in patients with or without extramedullary plasmocytoma (EMD) treated by IRD or RD regimen
See this image and copyright information in PMC

References

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