Blood: Oral ixazomib-lenalidomide-dexamethasone treatment of newly diagnosed multiple myeloma that cannot be transplanted

A continuous regimen based on lenalidomide-dexamethasone (Rd) is one of the standard treatments for newly diagnosed multiple myeloma (NDMM) patients who are not eligible for transplantation
.
The oral proteasome inhibitor ixazomib is suitable for continuous administration and has predictable and controllable toxicity

The TOURMALINE-MM2 trial is a double-blind, placebo-controlled clinical trial that recruited NDMM patients who were not eligible for transplantation.
They were randomly divided into two groups and received 4 mg of ixazomib (n=351) or placebo (n =354) Joint Rd
.
After 18 courses of treatment, dexamethasone was discontinued, and reduced-dose ixazomib (3 mg) and lenalidomide (10 mg) were continued until the disease progressed or intolerable toxicity

PFS rate of ixazomib-Rd group and placebo-Rd group

The median follow-up time for the ixazomib-Rd group and the placebo-Rd group were 53.
3 months and 55.
8 months, respectively, and the median PFS was 35.
3 vs 21.
8 months (hazard ratio [HR] 0.
830, 95%CI 0.
676 -1.
019; p=0.
073)
.
Compared with the placebo-Rd group, the ixazomib-Rd group had a complete response rate (26% vs 14%; odds ratio [OR] 2.

OS rate of ixazomib-Rd group and placebo-Rd group

Among the pre-designated high-risk cytogenetic subgroups, the median PFS of the ixazomib-Rd group and the placebo-Rd group were 23.

Adverse events requiring urgent treatment (TEAE) are mostly grade 1/2
.
88% vs 81% of patients in the ixazomib-Rd group and placebo-Rd group experienced a grade ≥3 TEAE, 66% vs 62% of the patients experienced a severe TEAE, and 35% vs 27% of the patients, respectively TEAE cases led to treatment interruption; 8% vs 6% of patients in the two groups died during the study period

In summary, the addition of ixazomib to the Rd regimen was tolerable, did not lead to new safety signals, and resulted in a clinically significant PFS benefit of 13.
5 months
.
All in all, ixazomib-Rd provides a new option for patients who can benefit from full oral triple therapy

Thierry Facon, et al.