Published Online:December 09, 2013
Treating newly diagnosed patients – even older ones – with a combination of lenalidomide, marketed by Celgene as Revlimid, and low-dose dexamethasone, a steroid, seems likely to become the new treatment standard for multiple melanoma, based on the presentation of a massive, multinational Phase III study1
presented Sunday at the 55th
American Society of Hematology Meeting and Exhibition in New Orleans. Lenalidomide is a vascular endothelial growth factor inhibitor.
Thierry Facon, MD, lead author on the abstract presented at the plenary session, outlined results from the FIRST Trial, which asked whether the standard of treating newly diagnosed older patients with melphalan and thalidomide first still makes sense. Dr Facon, of the Lille regional university in Lille, France, and his colleagues found it does not, based on results from 1623 patients from 243 cancer centers in 18 countries. In the study, sponsored by Celgene and the Intergroupe Francophone du Myelome (IFM), all patients were at least 65 and the median age was 73; this is key because the drug combination that FIRST examined has been used in younger patients, but not among older patients who make up most of the multiple myeloma population.
Patients were randomly assigned to 3 treatment groups: One received treatment with the lenalidomide-dexamethasone combination – called Lex-Dex – for 18 months, the second received treatment with melphalan, prednisone, and thalidomide (MPT) for 18 months, and the third received the Lex-Dex combo continuously, or until the disease progressed. Under current standards of care, therapy ends after several months because patients begin to experience side effects.
At 37 months, progression-free survival (PFS) among those taking the Lex-Dex combination continuously was 25.5 months. For the other 2 groups, PFS was almost the same; with the Lex-Dex group seeing 20.7 months on average and the MPT group seeing 21.2 months, which represented a 28% reduction in risk progression for the group taking Lex-Dex continuously.
In the session, Facon said that long-term results for overall survival are not yet mature, but at the 4-year mark, OS was 59.4% for the continuous Lex-Dex group, 55.7% for the group that received Lex-Dex for 18 months, and 51.4% for the MPT group.
What’s more, Dr Facon said, is that cytogenetic profiles show that 762 patients were high-risk; some were already suffering loss renal function. Unlike populations typically included in clinical trials, Dr Facon said, “this population is somewhat close to a real-life population.”
A capacity crowd filled the giant hall at the plenary session to hear Dr Facon’s presentation, after which a questioner commented, “This is a shift in the paradigm.” Adverse effects were dramatically reduced for the Lex-Dex groups compared to MPT, and remained “manageable” even for those on continuous therapy, Dr Facon said. Grade 3 and 4 events for the continuous Lex-Dex arm versus the MPT arm included: neutropenia, 28% versus 45%; thrombocytopenia, 8% versus 11%; infection, 29% versus 17%; neuropathy, 5% versus 15%; and deep-vein thrombosis, 5% versus 3%.
Despite the better results for continuous therapy in the trial, it is too soon to say whether it will become a standard with Lex-Dex therapy. Though less toxix than MPT, continuous therapy does present issues of side effects. But the bigger challenge may be cost: Revlimid prices range between $12,700 and $13,300 a month, based online pharmacy prices from GoodRx.
Facon T, Dimopoulos, MA, Dispenzieri, A, et al. Initial phase III results of the FIRST (frontline investigation of lenalidomide + dexamethasone versus standard thalidomide) in newly diagnosed multiple myeloma patients ineligible for stem cell transplantation. Abstract 2. American Society of Hematology 55th Meeting and Exhibition, New Orleans.