Addition of ixazomib to lenalidomide and dexamethasone in multiple myeloma − Data from real-world Czech practice

Introduction

This publication describes the extended follow-up results of two cohorts of patients with RRMM treated with either the double combination of lenalidomide and dexamethasone (RD) or with the addition of ixazomib (IRD). The median number of prior lines of therapy was 1, though a significant portion of patients received 4 or more previous lines.

In the analysis aimed at evaluating longer-term outcomes, new primary endpoints were defined – overall survival (OS), progression-free survival (PFS), and progression-free survival from the start of IRD/RD therapy to the second progression of the disease or death (PFS-2). Secondary endpoints included, for example, survival in patients pretreated with lenalidomide. The data collection cutoff for the analysis was March 2021.

Evaluated patient population

The cohort of RRMM patients included 344 individuals treated with either the combination with ixazomib (n = 127) or without it (n = 217). The ixazomib group was somewhat younger (median age 66.0 vs. 68.0 years; p = 0.002), with a higher proportion of patients undergoing autologous stem cell transplantation (62.0 vs. 43.3 %; p < 0.001) or having been previously treated with proteasome inhibitors (96.9 vs. 91.2 %; p = 0.047). The IRD group also had a higher incidence of extramedullary myeloma (14.2 vs. 6.7%, p = 0.034). Additionally, the initial dose of lenalidomide (LEN) was slightly higher in the ixazomib group. However, univariate and multivariate analyses did not show that these differing baseline characteristics affected patients' response rates and survival.

The median follow-up was 28.5 months for all patients, 31.7 months in the ixazomib group, and 26.0 months in the RD group.

Results

The overall response rate (ORR) was 73.0% for patients treated with ixazomib compared to 66.8% in the group without it (p = 0.275). The maximum response rates achieved were as follows: complete remission 11.9% (vs. 7.8%), very good partial response 23.8% (vs. 18.4%), partial response 34.9% (vs. 40.6%), and minimal response 9.5% (vs. 15.2%). The difference in achieving complete and very good partial response between groups was statistically significant (38.1 vs. 26.3%; p = 0.028).

Additionally, an improvement in median PFS was observed in the IRD group (17.5 vs. 12.5 months; p = 0.013). This improvement was more pronounced in patients with 1–3 prior relapses treated with ixazomib (22.3 vs. 12.7 months; p = 0.003). The best results were observed in patients with the first relapse, with the median PFS progressively declining in both groups for second and third relapses. The median PFS-2 was also significantly longer in the ixazomib group (29.8 vs. 21.6 months; p = 0.016).

The median OS for patients treated with ixazomib was 40.9 months (vs. 27.1 months; p = 0.001). Patients with 1-3 relapses achieved even better OS results (51.7 vs. 27.8 months; p < 0.001).

An analysis in the IRD group based on prior lenalidomide treatment was also performed. The median PFS for patients pretreated with lenalidomide (n = 22) versus those not previously treated with lenalidomide (n = 105) was 8.7 vs. 23.1 months (p = 0.001) and the median OS 13.2 vs. 51.7 months (p = 0.030).

Conclusion

The IRD regimen was easily applicable, well-tolerated by patients, and provided very good treatment outcomes. The addition of ixazomib likely deepened the treatment response. The extension of PFS with IRD therapy subsequently translated into an extension of OS. As expected, patients pretreated with lenalidomide achieved poorer results. The outcomes of this real-world clinical practice observation were similar to those obtained in clinical trials.

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Source: Minařík J., Radocha J., Jungová A. et al. Ixazomib, lenalidomide and dexamethasone in relapsed and refractory multiple myeloma in routine clinical practice: extended follow-up analysis and the results of subsequent therapy. Cancers 2022; 14 (20): 5165, doi: 10.3390/cancers14205165.