Ixazomib, lenalidomide, and dexamethasone as first-line therapy: Tourmaline-MM2 trial update

Visual abstract

 

Most treatment options for newly diagnosed patients with multiple myeloma (NDMM) who are ineligible for transplant involve lenalidomide and dexamethasone (Rd-)based regimens. Rd in combination with proteasome inhibitors (PIs) have demonstrated beneficial results in survival outcomes; however, long-term use of injectable PI agents can be challenging for some patients. An all-oral triplet combination would reduce the need for patients to travel to the clinic as often and reduce the disease burden.

In a recent article in Blood, Thierry Facon and colleagues discussed the results of the Tourmaline-MM2 trial (NCT01850524), which tested the triplet combination of ixazomib-Rd against placebo-Rd in transplant-ineligible patients with NDMM.¹

The Multiple Myeloma Hub previously provided a detailed summary of the results of the Tourmaline-MM2 trial, here. This report provides a short update.

Measurable residual disease (MRD) and survival outcomes

Further results were reported with respect to MRD in this update. In the placebo-Rd arm, 17.5% of patients had a bone marrow aspirate taken compared with 28.8% of patients in the ixazomib-Rd arm. These samples were used for MRD evaluation by flow cytometry with a sensitivity of 10^–5. Of these patients, it was found that:

• 52.5% of patients in the ixazomib-Rd arm were MRD negative.
• 38.7% of patients in the placebo-Rd arm were MRD negative.

In the intention-to-treat population, this resulted in MRD negative rates of:

• 15.1% in the ixazomib-Rd arm.
• 6.8% in the placebo-Rd arm.

Median overall survival was not reached in either arm. Time to progression and time to response were significantly improved in the treatment arm compared with the placebo arm. Duration of response was also increased from 37.5 in the placebo-Rd arm to 50.6 months in the ixazomib-Rd arm (Table 1).

Table 1. Survival outcomes between treatment arms*

d, dexamethasone; R, lenalidomide. *Data from Facon et al.
	Ixazomib-Rd (n = 351)	Placebo-Rd (n = 354)	p value
Time to progression, months	45.8	26.8	p = 0.008
Time to response, months	1.0	1.9	p < 0.001
Duration of response, months	50.6	37.5	—

Conclusion

Ixazomib-Rd was demonstrated to be an effective treatment for transplant-ineligible patients with NDMM, with 15.1% of patients in the treatment arm reaching MRD-negativity at 10^–5. For patients with reduced mobility who find daily travel to the clinic difficult, this all-oral triplet combination could be a preferable treatment option.