P959: maintenance therapy followed autologous stem cell transplantation by ixazomib and/or lenalidomide in patients with newly diagnosed multiple myeloma: a multicentered real world study in china

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Maintenance therapy further deepens response and prolongs survival in patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT). In addition to lenalidomide, Ixazomib is ideally appropriate as a maintenance agent given its oral convenient and low toxicity. However, the advantage of combining Ixazomib and lenalidomide as maintenance was indeterminate, especially in high-risk patients. Aims: we aimed to assess the safety, tolerability, and efficacy of maintenance therapy with Ixazomib, Lenadomide, and Ixazomib in combination with lenalidomide respectively in newly diagnosed multiple myeloma (NDMM) undergoing ASCT. Methods: This study was approved by the Institutional Review Board of Peking Union Medical College Hospital and registered (NCT04217967).This multicenter retrospective study was conducted in 8 hospitals in China. NDMM patients after ASCT were treated with any of the maintenance regimens until progression: Ixazomib (I 4mg d1,8,15); Lenalidomide (R 25mg d1-14); or dual-drug combination (IR as above doses) 4 weeks a cycle. Primary endpoints were overall response rate (ORR) and minimal residual disease(MRD). The secondary endpoints included progression free survival (PFS), overall survival (OS), and safety profiles. Results: From April 2014 to Dec 2022, 152 cases were enrolled with a median follow-up of 30 (9-109) months. There were 152 patients in this cohort who received I (n=33), R (n=83),or IR (n=36) for maintenance. The proportions of high-risk population were 48.5% (16/33),25.3% (21/83), 47.2% (17/36) in I group, R group, and IR group respectively. The ORRs were all 100% in each group. The complete response (CR) rate before maintenance was 75%, 68% and 60% in I,R,IR group respectively, and further improved to 77%, 72% and 63%. The rates of MRD negativity were 83%, 66% and 50% before and 79%,75% and 67% after maintenance treatment. Till this end of follow-up in Feb 2023, 10 deaths occurred. The median OS were not achieved, and the median PFS were 44.8m,58.1m, and 59.0m in I,R,IR group respectively, while no statistical difference was observed between three groups. 54 MM defined as high risk at least one of the following:t(4;14),del(17/17p),t(14;16),t(14;20),and gain(1q).98 patients defined as standard risk without cytogenetic abnormalities.The median PFS in high-risk patients was 59.0m, comparable to 51.7m in standard risk group (p=0.489). In terms of high-risk patients in 3 groups, the median PFS were 49.7m, not reached, and 59.0m (P=0.846). During maintenance treatment, 24.2% (8/33), 20.5%(17/83), and 16.7%(6/36) of patients in I,R,IR group respectively reported adverse reactions(AEs). The main AEs were gastrointestinal diseases (4/8) in I group, rash in R group(7/17), and peripheral neuropathy in IR group (3/6). Summary/Conclusion: Maintenance treatment followed transplantation improves response and retards relapse. As demonstrated in this multicenter real-world study, the median PFS by the three maintenance regimens is 44 months or above, and OS is not reached. Greater rate of MRD negativity has achieved after maintenance. The median PFS in high-risk group is comparable to that of the standard risk group, indicating that maintenance therapy might close the gap. All regimens are well-tolerated. Analysis of subgroups needs to be conducted in larger population since biases are complex in real-practice.Keywords: Maintenance, Autologous peripheral blood stem cell tansplantati, Multiple myeloma