Adding Vorinostat to Lenalidomide Maintenance Does Not Improve Myeloma Survival

Adding vorinostat to lenalidomide maintenance therapy did not improve survival over lenalidomide maintenance alone in patients with newly diagnosed multiple myeloma, according to results from the Myeloma XI trial.

The phase III, multicenter, open-label, parallel-group, randomized, controlled Myeloma XI trial “aimed to evaluate whether the addition of the histone deacetylase inhibitor vorinostat to the lenalidomide maintenance backbone could improve outcomes further,” the study’s authors wrote.

The researchers randomized patients to receive maintenance therapy with lenalidomide 10 mg/day on days one through 21 of each 28-day cycle (n=307) or lenalidomide 10 mg/day on days one through 21 of each cycle plus vorinostat 300 mg/day on days one through seven and days 15 through 21 of each 28-day cycle (n=307). Patients continued to receive treatment until “unacceptable toxicity” or progressive disease, according to the Myeloma XI trial investigators.

Patients receiving lenalidomide plus vorinostat had a median PFS of 34 months, while those receiving lenalidomide alone had a median PFS of 40 months (hazard ratio [HR], 1.18; 95% CI, 0.96-1.44; P=.109).

There was no significant difference in the median OS between patients receiving lenalidomide plus vorinostat (not estimable) or lenalidomide alone (75 months; HR, 0.99; 95% CI, 0.76-1.29; P=.929).

The combination treatment “appeared to be poorly tolerated with more dose modifications, fewer cycles of maintenance therapy delivered and higher rates of discontinuation due to toxicity than lenalidomide alone,” the study’s authors wrote.

The Myeloma XI trial did not meet its primary endpoint, according to the researchers.

“This analysis of the Myeloma XI trial demonstrates that the addition of vorinostat to lenalidomide did not significantly improve PFS or OS, with a trend towards an impaired PFS associated with lenalidomide-vorinostat compared to lenalidomide alone being seen in the younger patients,” the investigators concluded.

Reference

Jenner MW, Pawlyn C, Davies FE, et al. The addition of vorinostat to lenalidomide maintenance for patients with newly diagnosed multiple myeloma of all ages: results from “Myeloma XI”, a multicentre, open-label, randomised, phase III trial. Br J Haematol. 2022. doi:10.1111/bjh.18600