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Lenalidomide (Revlimid)
Lenalidomide may be the best maintenance treatment option for patients with newly diagnosed multiple myeloma (MM), according to the authors of a systematic review and meta-analysis.
Francesca M. Gay, MD, PhD, of the University of Torino in Italy, and her coauthors wrote that, despite the well-recognized importance of novel agent–based maintenance therapy for MM, there is a lack of direct or indirect comparisons between the available regimens.
In a paper published in JAMA Oncology, the researchers reported the results of a systematic review and meta-analysis of 11 prospective, phase 3, randomized, controlled trials of 8 varieties of maintenance therapy in 5073 participants with newly diagnosed MM.
The researchers found that lenalidomide-based regimens showed the best progression-free survival rates, compared with placebo. The hazard ratio (HR) was 0.39 for lenalidomide plus prednisone, and the HR was 0.47 for lenalidomide alone.
In 74% of the network meta-analysis simulations, lenalidomide-based regimens were the most effective options.
Four other maintenance treatment options—thalidomide-interferon (HR, 0.50), thalidomide-bortezomib (HR, 0.58), bortezomib-prednisone (HR, 0.72), and thalidomide alone (HR, 0.73)—also showed progression-free survival gains, but interferon therapy (HR, 0.91) failed to show any benefit.
For overall survival, lenalidomide alone (HR, 0.76) was the best option, followed by thalidomide-bortezomib (HR, 0.82) and bortezomib-prednisone (HR, 0.84). None of the other regimens considered showed benefits for overall survival.
“Long-term use of lenalidomide undoubtedly has advantages, owing to the lack of neuropathy, which is the main factor limiting the long-term use of both thalidomide and bortezomib,” the authors wrote.
When the authors restricted their analysis to trials conducted in the setting of autologous stem cell transplant, they found similar results, with lenalidomide-based regimens having the best progression-free and overall survival.
Patients with a good prognosis and standard-risk chromosomal abnormalities also did best with lenalidomide-based maintenance, while those with a poor prognosis—for example, with ISS stage III disease—benefited more from bortezomib-based maintenance.
However, patients with high-risk chromosomal abnormalities gained no advantage from any regimen, which the authors suggested may relate to small sample size, different cut-off points, or the patients’ extremely poor prognosis.
The authors noted that their analysis did not take into account adverse events, drug discontinuations, or quality of life but focused solely on progression-free survival and overall survival.
“An increase in second primary malignant disease with prolonged lenalidomide therapy has been reported, but the survival benefit overcame the risk in all the trials,” they wrote.
The authors also commented that better treatment options are needed for patients with aggressive disease, and there are ongoing trials looking at second-generation proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies for maintenance therapy.
Most authors declared research funding, advisory board positions, fees, and honoraria from the pharmaceutical industry, including lenalidomide manufacturer Celgene.