In-class transition from bortezomib to ixazomib-based regimens in transplant-ineligible patients with newly diagnosed multiple myeloma: A retrospective, observational, real-world study conducted in China Free

Background

Proteasome inhibitors (PIs) are cornerstone therapeutic agents in the management of multiple myeloma. Given that myeloma typically necessitates long-term treatment, intravenous PIs such as bortezomib are often associated with treatment discontinuation due to adverse events (AEs). For transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM), transitioning from initial bortezomib (V)-based induction therapy to a regimen incorporating the oral proteasome inhibitor ixazomib may provide a more convenient and sustainable approach to prolonged PI therapy, while maintaining favorable efficacy and safety profiles. This real-world study aims to evaluate the efficacy and safety of such a transition strategy in this patient population.

Method

This ongoing study is a single-center, non-interventional, retrospective analysis conducted on patients diagnosed with multiple myeloma (MM), utilizing data from the Chinese National Longitudinal Cohort of Haematologic Diseases (NICHE)-MM registry. This registry is a longitudinal database maintained by the Institute of Haematology, Blood Diseases Hospital (IHBDH) in China. The retrospective analysis included adult patients aged ≥18 years with transplant-ineligible NDMM who underwent an in-class transition from bortezomib to ixazomib-based regimens between April 12, 2018, and March 31, 2024. Data were obtained from the NICHE-MM registry. The primary endpoint of the study was the overall response rate (ORR). Secondary endpoints encompassed progression-free survival (PFS) and overall survival (OS).

Results

A total of 107 transplant-ineligible patients with NDMM received initial induction therapy with bortezomib-based regimens, followed by a transition to ixazomib-based continuous therapy. The median age was 63 years (range: 33–80), with 49% of the patients being male. The majority (77%) had an ECOG performance status of 0–1. Additionally, 36% of patients were classified as ISS stage III, 24% had R-ISS stage III disease. Comorbidities were observed in 52% of patients, including hypertension (48%), renal disorders (23%), cardiovascular disorders (29%), diabetes (16%), liver disorders (23%), and cerebrovascular diseases (4%).

Patients received a median duration of 3.4 months (range: 0.1–16.3 months) of initial treatment with V-based regimens. The most common V-based regimens included VRd (bortezomib, lenalidomide, dexamethasone, 48.6%), Vd (bortezomib, dexamethasone, 28.0%), VCd (bortezomib, cyclophosphamid, dexamethasone, 23.4%), VAd (bortezomib, Aclarubicin, dexamethasone, 11.2%), and others. Following initial treatment, patients transitioned to ixazomib (I)-based regimens for continuation therapy. The most frequently used I-based regimens were IRd (Ixazomib, lenalidomide, dexamethasone, 50.5%), Id (Ixazomib, dexamethasone, 31.8%), ICd (Ixazomib, cyclophosphamid, dexamethasone, 7.5%), and others. The ORR following the treatment transition was 79%. Among these patients, 68% achieved a very good partial response (VGPR) or better, and 47% achieved a complete response (CR). As of March 31, 2025, with a median follow-up of 34.9 months, the median PFS was 38.0 months (95% CI: 28.78, not reached), with a 12-month PFS rate of 80%. The median OS had not been reached, and the 12-month OS rate was 92%.. The safety profile of ixazomib was consistent with findings from previous clinical trials.

Conclusion

The findings of our real-world study conducted in China align with those of the US-MM6 real-world study carried out in the U.S. population. This observational study involving transplant-ineligible NDMM patients in China indicates that switching from bortezomib to ixazomib-based regimens allows for extended continuous PI-based therapy, offering favorable efficacy, acceptable safety, and enhanced treatment convenience. Despite the presence of multiple comorbidities among the patient cohort, this therapeutic strategy may serve as a viable treatment option for individuals with transplant-ineligible NDMM.