Treatment outcomes in patients with newly diagnosed multiple myeloma receiving ixazomib as initial therapy: A retrospective, observational, real-world historical database analysis from China

Abstract Background Multiple myeloma (MM) is a malignant and life-threatening disorder of plasma cells, characterized by the clonal proliferation of abnormal plasma cells and the overproduction of monoclonal immunoglobulins. Proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) are currently considered cornerstone therapies for transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM), and are preferentially recommended in major clinical guidelines. Ixazomib (I), an orally administered proteasome inhibitor, has demonstrated promising efficacy and a manageable safety profile in clinical trials. However, there is limited real-world evidence on the use of ixazomib-based regimens as initial treatment for transplant-ineligible NDMM patients. This study aims to evaluate the efficacy and safety of ixazomib-based regimens in routine clinical practice in China. Method This study is an ongoing, single-center, non-interventional, retrospective database analysis focusing on MM patients identified from the Chinese National Longitudinal Cohort of Haematologic Diseases (NICHE)-MM registry. The NICHE-MM registry is an updated longitudinal data repository maintained by the Institute of Haematology and Blood Diseases Hospital (IHBDH). The study included patients aged 18 years or older with a confirmed diagnosis of MM who received an ixazomib-based regimen as initial treatment between April 12, 2018, and March 31, 2024. Patients enrolled in clinical trials were excluded. The primary objective of this study was twofold: 1) to evaluate treatment patterns and responses across lines of therapy, and 2) to assess time-to-event outcomes, including progression-free survival (PFS), overall survival (OS), and duration of therapy. Results A total of 431 patients were enrolled in the study, among whom 146 transplant-ineligible NDMM patients commenced treatment with Ixazomib-based regimens. The patients were recruited from various regions, including North China, Northeast China, East China, Central China, and Northwest China. The median age was 64 years, ranging from 28 to 83 years, with 55% of the patients being male. 77% of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 49% were classified as International Staging System (ISS) stage III. About 65% of the patients had at least one comorbidity, with the most common being hypertension (38%), renal disorders (35%), cardiovascular diseases (31%), diabetes (18%), and liver disorders (17%). Ixazomib-based regimens consisted of combinations such as Ixazomib plus IMiD with or without other agents (e.g., IR[Ixazomib, lenalidomide], ITd[Ixazomib, thalidomide, dexamethasone], IPd[Ixazomib, pomalidomide, dexamethasone], IRAd[Ixazomib, lenalidomide, aclarubicin, dexamethasone], IRCd[Ixazomib, lenalidomide, cyclophosphamid, dexamethasone]) and Ixazomib plus dexamethasone with or without additional agents (e.g., ICd[Ixazomib, cyclophosphamid, dexamethasone], IACd[Ixazomib, aclarubicin, cyclophosphamid, dexamethasone], Id + epirubicin, ICd + epirubicin , Id + denosumab, IMd[Ixazomib, melphalan, dexamethasone]). The overall response rate (ORR) was 82%, with 51% of patients achieving a very good partial response (VGPR) or better and 32% achieving a complete response (CR). The median time to response was 1.6 months. As of March 31, 2025, with a median follow-up duration of 16.4 months (range: 0.4–77.7 months), the data were not yet mature. The median PFS was 24.2 months (95% CI: 21.00, not reached), with a 12-month PFS rate of 81%. The median OS had not been reached, and the 12-month OS rate was 98%. Approximately 76% of patients maintained a 4 mg dose of Ixazomib throughout treatment, and treatment-related adverse events were generally manageable. Conclusion Ixazomib-based regimens demonstrate favorable efficacy and tolerability in real-world clinical practice among transplant-ineligible NDMM patients in China, with treatment outcomes comparable to those reported in the randomized controlled trials. Survival outcomes remain under ongoing follow-up. These findings suggest that ixazomib-based therapy may serve as a viable first-line treatment option, even for patients with comorbid conditions.