|The following article features coverage from the American Society of Hematology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Ixazomib plus lenalidomide and dexamethasone (IRd) resulted in durable responses and trended toward improved progression-free survival (PFS) among patients with newly diagnosed multiple myeloma (MM) who were ineligible for transplant, according to the results of the phase 3 TOURMALINE-MM2 trial presented at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.
“Patients with newly-diagnosed MM who are not eligible for transplant are a diverse population and so treatment must be adapted to individual patients,” Thierry Facon, MD, of the University of Lille in France, and presenter of the study, said. “An all-oral proteosome inhibitor-lenalidomide/dexamethasone treatment may be useful for patients who do not want to or who are unable to travel to the clinic frequently,” he added.
The multicenter, double-blind phase 3 TOURMALINE-MM2 trial (ClinicalTrials.gov Identifier: NCT01850524) randomly assigned 705 patients with newly diagnosed MM ineligible for transplant to receive IRd or placebo plus lenalidomide and dexamethasone (Rd). The primary endpoint was PFS and secondary endpoints included overall survival (OS), complete response (CR) rate, overall response rate (ORR), and safety.
The median age of patients at baseline was 74 years, with 44% of patients 75 years or older. Stage III disease was present among 17% of patients, and expanded high-risk cytogenetics was present in 40%.
The ORR was similar between groups, at 82.1% with IRd compared with 79.7% with lenalidomide and dexamethasone (Rd). However, more patients achieved a CR/stringent CR and at least a very good partial response with IRd, at 25.6% and 63%, respectively, compared with 14.1% and 47.7%, respectively, in the Rd arm. The median duration of response was 50.6 months with IRd compared with 37.5 months with Rd.
IRd treatment resulted in a trend toward longer PFS compared with Rd, with a median of 35.3 months compared with 21.8 months, respectively (hazard ratio [HR], 0.830; 95% CI, 0.676-1.018; P =.073), but it was not significant. In a prespecified subgroup analysis, treatment of patients with expanded high-risk cytogenetics (HR, 0.690; 95% CI, 0.506-0.941; P =.019) or creatinine clearance of 60 mL/min or less (HR, 0.625; 95% CI, 0.450-0.869) with IRd resulted in significantly prolonged PFS compared with Rd.
Time to progression was also longer with IRd, with a median of 45.8 months compared with 26.8 months with Rd (HR, 0.738; 95% CI, 0.589-0.925; P=.008).
The median OS was not yet reached with in either treatment arm with a median follow-up of approximately 58 months.
The majority of treatment-emergent adverse events (TEAEs) were mild to moderate in severity. The most common grade 3 or higher TEAEs that were more common with IRd were neutropenia, rash, thrombocytopenia, and diarrhea. Treatment discontinuation due to TEAEs occurred among 35% of patients treated with IRd and 26.9% of patients treated with Rd.
Dr Facon concluded that “addition of ixazomib to Rd in patients with newly diagnosed MM led to a clinically meaningful PFS benefit, with a 13.5-month improvement in the median.” He added that the combination “is a feasible treatment option for certain transplant-ineligible patients with newly diagnosed MM who could benefit from an all-oral triplet combination.”
Plus, he said, “An all-oral [proteosome inhibitor]-Rd triplet may be useful for patients who prefer not to or cannot travel to clinic frequently.”
Disclosures: Some of the presenters disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the presentation abstract.
Read more of Cancer Therapy Advisor‘s coverage of the ASH 2020 meeting by visiting the conference page.
Facon T, Venner CP, Bahlis N, et al. The phase 3 TOURMALINE-MM2 trial: oral ixazomib, lenalidomide, and dexamethasone (IRd) vs placebo-Rd for transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). Presented at: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-9, 2020. Abstract 551.