Molecular Profiling Aids in Determining Which Patients With Multiple Myeloma Will Benefit From Lenalidomide Maintenance

Among patients with multiple myeloma who undergo autologous stem cell transplant (ASCT), the presence of some genetic markers, including del(1p), may indicate a high likelihood of benefitting from lenalidomide maintenance, according to research published in Blood.

Lenalidomide is currently the only licensed maintenance therapy for MM after ASCT among newly-diagnosed patients. There is, however, some question as to which patients should receive lenalidomide, given it is associated with cytopenias, vascular events, diarrhea, an increased risk of second cancer — and a high rate of financial toxicity, particularly when administered over a long period.

Although previous research has suggested an overall clinical benefit in large, heterogenous groups of patients, it is unclear which patient subgroups are the most likely to have optimal outcomes.

For this study, researchers in the United Kingdom conducted a retrospective analysis on data from the National Cancer Research Institute Myeloma XI (MyXI) trial to determine whether any molecular markers predict a lenalidomide response among patients with MM who undergo ASCT.

Overall, data from 556 patients were included. In the MyXI trial cohort, 65% of patients were male sex, 44% of patients had a World Health Organization performance status score of 0, and 71% had a Revised International Staging System disease grade of 2.

As part of the MyXI trial, 65% of patients were randomly assigned to receive lenalidomide while 35% of patients were assigned to observation. Molecular profiles were as follows: 14% of patients had t(4:14), 3.6% of patients had t(14;16)/t(14;20), 10% of patients had del(1p), 8.3% of patients had del(17p), and 33% of patients had gain(1q); 17% of patients had double-hit MM (at least 2 markers), 32% had single-hit MM, and 51% had no marker.

Patients with single-hit MM had the greatest rate of responding to lenalidomide in the cohort. Patients with single-hit del(1p), del(17p), and t(4;14) had an approximately 40-fold, 10-fold, and 7-fold risk reduction for disease progression or death, respectively, compared with the observation cohort.

These findings corresponded to a median progression-free survival of 57.3 months in the lenalidomide maintenance group vs 10.9 months for observation.

“To identify these patients, but also those with double hit, who are in need of novel maintenance approaches, extended profiling at diagnosis should be considered for all patients with [newly diagnosed] MM who are eligible for transplantation, with a minimum requirement of t(4;14), t(14;16)/t(14;20), del(1p), gain(1q), and del(17p) assessment, all of which are clinically accessible,” the authors wrote in their report.

Disclosures: This research was supported by Janssen and Takeda. Please see the original reference for a full list of disclosures.

Reference

Panopoulou A, Cairns DA, Holroyd A, et al. Optimizing the value of lenalidomide maintenance by extended genetic profiling: an analysis of 556 patients in the Myeloma XI trial. Blood. 2023;141(14):1666-1674. doi:10.1182/blood.2022018339

This article originally appeared on Hematology Advisor