Dr Zonder on the Real-World Use of Ixazomib-based Therapy in R/R Multiple Myeloma

Jeffery Zonder, MD, leader, Multiple Myeloma Sub-committee, Barbara Ann Karmanos Cancer Institute, professor of medicine, Departments of Hematology and Oncology, Wayne State University School of Medicine, discusses the real-world use of ixazomib (Ninlaro)-based therapy for patients with relapsed/refractory multiple myeloma as seen in the INSURE study.

Within multiple myeloma, data reported with certain regimens in clinical trials can often differ from patient responses in the real world, Zonder begins. Many clinical trials exclude patients with common health problems, and about 72% of patients with relapsed or refractory multiple myeloma do not meet the stringent eligibility criteria for randomized clinical trials, Zonder states. Accordingly, these conditions increase frailty, worsen a patient's ability to respond to or tolerate a given therapy, and increase difficulties associated with drug delivery, Zonder explains.

The INSURE study was designed to address this discrepancy and provide a more comprehensive comparison of survival outcomes seen with ixazomib, lenalidomide (Revlimid), and dexamethasone (IRd) in the real-world setting vs in clinical trials, Zonder continues. The study pooled datasets from the INSIGHT MM (NCT02761187), the phase 2 UVEA-IXA (NCT03439293), and REMIX (NCT03433001) observational studies of IRd, and compared these with combination's efficacy in the phase 3 TOURMAILINE-MM1 study (NCT01564537).

Findings from TOURMALINE-MM1 previously supported the FDA’s approval of IRd for patients with relapsed or refractory multiple myeloma in 2015. In this trial, patients who received IRd achieved an overall response rate (ORR) of 78%. Moreover, median progression-free survival was 20.6 months in these patients.

The analysis showed that real-world outcomes and toxicities seen with IRd were comparable with those reported in TOURMAILINE-MM1, Zonder reports. Of the 564 patients included in INSURE, the median PFS and ORR was 19.9 months (95% CI, 16.6-23.6) and 65%, respectively. Additionally, patients had a median overall time to next treatment (TTNT) in the real-world setting of 18.4 months overall (95% CI, 15.3-20.8). Patients who received IRd in earlier lines vs later lines had a numerically larger TTNT.

Results from INSURE confirm the accuracy of data from TOURMALINE-MM1, supporting the utilization of this regimen in clinical practice, Zonder concludes.