Real-World Data of Maintenance Therapy for Newly Diagnosed Multiple Myeloma: Ixazomib Versus Lenalidomide

Introduction: Lenalidomide and ixazomib are both effective maintenance therapy options for patients with multiple myeloma (MM). However, there is a lack of clinical studies directly comparing the efficacy and safety of these two agents. In this report, we present real-world data on the maintenance therapy of lenalidomide versus ixazomib in patients with newly-diagnosed MM (NDMM). Methods: A retrospective real-world analysis was carried out between September 25, 2019 and June 20, 2023. The study included multiple myeloma patients who achieved a best response of partial response (PR) or higher following induction and/or consolidation therapy. Ixazomib was administered at a weekly dose of 3-4mg for 3 doses within a 28-day cycle, and lenalidomide was given at a daily dose of 10-25mg until disease progression. Adverse events were graded based on CTCAEv4.0 criteria, with the primary endpoints focusing on progression-free survival (PFS) and the incidence of adverse events. Results: A total of 115 patients with NDMM were included, with 60 patients receiving ixazomib and 55 patients on lenalidomide maintenance. The patients' characteristics, cytogenetics, and disease staging between groups were well-balanced. The median follow-up periods were 33 and 29 months for the ixazomib and lenalidomide groups, respectively. There was no significant difference in PFS between the ixazomib and lenalidomide groups, with a median PFS of 39 versus 35 months, P=0.706. Following ixazomib maintenance, 35 out of 60 patients (58.3%) reached a response of ≥CR, while 56 patients (93.3%) achieved ≥VGPR, and 23 patients (38.3%) experienced a deepened response. After lenalidomide maintenance, 29 patients (52.7%) achieved ≥CR, 49 patients (89.1%) achieved ≥VGPR, and 15 patients (27.3%) showed an improved response. Subgroup analysis revealed that cytogenetic risk, R-ISS staging, ASCT, extramedullary disease, and remission status prior to maintenance did not have a significant impact on median PFS between the lenalidomide and ixazomib groups. In the lenalidomide group, high-risk cytogenetics were correlated with a shorter median PFS compared to standard-risk (SR) ,18 months vs. 35 months, P=0.022; whereas this association was not observed in the ixazomib group, HR vs. SR: 35 months vs. not reached, P=0.543. The incidence of neutropenia in the ixazomib group was lower than in the lenalidomide group, 35.1% vs. 58.5%, P=0.014. No severe drug-related AEs were reported in either group, and there were no statistically significant differences in non-hematological AEs between the two groups. Conclusion: In patients with NDMM, maintenance therapy utilizing ixazomib or lenalidomide results in similar response rates and progression-free survival (PFS). Ixazomib appears to mitigate the adverse impacts of high-risk cytogenetics while maintaining a manageable toxicity profile.