medwireNews: Lenalidomide offers the best overall (OS) and progression-free survival (PFS) among novel agent-based maintenance regimens in patients with newly diagnosed multiple myeloma, according to a systematic review and network meta-analysis.
The analysis, reported in JAMA Oncology, included data on 5073 patients from 11 prospective phase III randomized controlled trials, published over the past 20 years, that together evaluated the use of eight different regimens for maintenance therapy.
The network meta-analysis simulations for OS analysis identified lenalidomide monotherapy as the best choice, based on the trifecta of a 24% decreased risk of death compared with no maintenance or placebo, a median ranking distribution of 2, and a 38% probability of being the best treatment.
Thalidomide–bortezomib and bortezomib–prednisone were the next best regimens, with the risk of death reduced by 18% and 16%, respectively. The other regimens of lenalidomide–prednisone, thalidomide–interferon, thalidomide alone, and interferon alone showed no OS benefits.
Lenalidomide-based regimens were also associated with the best PFS advantage, with the risk of progression significantly reduced by 61% for lenalidomide–prednisone and 53% for lenalidomide alone compared with no maintenance or placebo. These treatments were first and second, respectively in median ranking, and together were the most effective options in 74% of simulations.
Thalidomide–interferon, thalidomide–bortezomib, bortezomib–prednisone, and thalidomide alone also gave hazard ratios in favor of maintenance therapy for PFS. Interferon alone, however, did not show any PFS benefit as maintenance therapy.
Subgroup analyses suggested that while lenalidomide-based maintenance remained the best option in patients with a good prognosis (International Staging System [ISS] stage I/II disease) and standard-risk chromosomal abnormalities, those with a poor prognosis (ISS stage III disease) may derive a greater benefit from bortezomib-based maintenance. The study failed to detect an advantage for any regimen over no maintenance or placebo in patients with high-risk chromosomal abnormalities.
Discussing these findings, Francesca Gay (University of Torino, Italy) and colleagues note that “it remains to be defined as to whether all patients require maintenance therapy or not or, most importantly, if the choice of the agent/s should be dictated by disease characteristics.” And they say that “we cannot conclude that lenalidomide alone is sufficient for high-risk patients and a better choice would probably be to combine lenalidomide with proteasome inhibitors, instead of using only 1 agent.”
Nonetheless, the team concludes: “Despite the assumptions and limitations of this [network meta-analysis], our results support the use of lenalidomide maintenance therapy in most patients.”
By Catherine Booth
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