Ixazomib combined with daratumumab-based regimens as first-line therapy for transplant-ineligible patients with newly diagnosed multiple myeloma: A real-world historical database analysis from China

Abstract Background Emerging novel therapies have significantly improved survival in patients with multiple myeloma (MM), and treatment guidelines have been updated to reflect these advances. Novel agents, including proteasome inhibitors (PIs), immunomodulatory drugs (IMDs), and anti-CD38 monoclonal antibodies, now constitute the cornerstone of MM treatment and have markedly enhanced patient prognosis. Ixazomib, the first oral PI, was approved due to its robust efficacy and favorable safety profile. However, data on the combination of ixazomib (I) and daratumumab (D) as a frontline treatment for transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) remain limited. This study aims to provide real-world evidence regarding the efficacy and safety of this combination therapy in that specific patient population. Method This study is an ongoing, single-center, non-interventional, retrospective analysis conducted among patients diagnosed with multiple myeloma (MM). The data were extracted from the Chinese National Longitudinal Cohort of Haematologic Diseases (NICHE)-MM registry, which is maintained by the Institute of Haematology and Blood Diseases Hospital (IHBDH). The analysis included patients aged ≥18 years who were NDMM and initiated treatment with ixazomib in combination with daratumumab-based regimens as their first-line therapy between April 12, 2018, and March 31, 2024. The primary endpoint of the study was the overall response rate (ORR), and secondary endpoints included progression-free survival (PFS). Results Among transplant-ineligible NDMM patients who initiated treatment with a DI-based regimen (n=31), the median age was 60 years (range: 34–83), with 55% being male. 68% of patients had an ECOG performance status of 0–1, 48% of patients had ISS stage III disease, and 26% had R-ISS stage III disease. Comorbidities were present in 68% of patients, including hypertension (43%), renal disorders (38%), cardiovascular disorders (24%), diabetes (33%), liver disorders (10%), and cerebrovascular diseases (5%). The DI-based regimens included DICd (C: cyclophosphamide; d: dexamethasone) plus vinorelbine (VDS), DId plus VDS, DId plus denosumab, DId plus venetoclax (VEN), DIPd (P: pomalidomide), DIR (R: lenalidomide), and DIRd plus VEN. The ORR was 89%, with 74% achieving very good partial response (VGPR) or better and 48% achieving complete response (CR). The median time to response was 1.2 months. As of March 31, 2025, the median follow-up was 20.7 months (range: 2–59.6). The median PFS was not reached (21.98, not reached), with a 12-month PFS rate of 89%. The median OS was not reached, and the 12-month OS rate was 100%. Conclusion The DI-based regimen, as an initial treatment option for transplant-ineligible NDMM patients, demonstrates efficacy comparable to that observed in previous prospective randomized controlled trials (RCTs) (NCT03012880, NTR6297, ORR: 71–96%). This real-world study conducted in China further supports the promising efficacy and acceptable safety profile of the ixazomib plus daratumumab-based regimen as a first-line treatment for transplant-ineligible NDMM patients in routine clinical practice, including among elderly patients with multiple comorbidities.