Dr. Leleu has received lecture fees and a research grant from Celgene and Janssen.
Study Title:
Study to Determine Efficacy and Safety of Lenalidomide Plus Low-Dose Dexamethasone Versus Melphalan, Prednisone, Thalidomide in Patients With Previously Untreated Multiple Myeloma (FIRST)
ClinicalTrials.Gov Identifier:
Coordinator:
Thierry Facon, Hopital Huriez, CHRU, Lille, France
Sponsors and Collaborators:
Intergroupe Francophone du Myélome (IFM) and Celgene Corporation
Participating Centers:
This study is being conducted in 281 medical centers worldwide.
Accrual Goal:
This study has reached its enrollment goal and is no longer recruiting participants. A total of 1,623 patients have been enrolled.
Study Design:
Multicenter, open-label, randomized, phase III study to determine the efficacy and safety of lenalidomide plus low-dose dexamethasone (Rd) when given either until disease progression or for a total of 18 four-week cycles versus the combination of melphalan, prednisone, and thalidomide (MPT) given for a total of 12 six-week cycles in patients with previously untreated multiple myeloma who are either 65 years of age or older or who are not candidates for stem cell transplantation. The primary endpoint is progression-free survival (PFS), with the hypothesis that Rd until progression will prolong PFS as compared with MPT.
Rationale:
In recent years, significant progress has been observed in the treatment of myeloma in elderly patients with the incorporation of either bortezomib (Velcade®; V) or immunomodulatory drug (either thalidomide [T] or lenalidomide [Revlimid®; R]) onto the historical platform of melphalan and prednisone (MP). Two of these regimens, MP+V and MP+T, have been approved in Europe and, compared with MP, have shown significant improvement both in response rates and, more importantly, in survival. However, these two regimens have demonstrated a peculiar neurotoxicity profile that renders their efficacy:toxicity ratio suboptimal. Studies from the U.S. ECOG group have demonstrated a significant improvement in the toxicity profile, without loss of efficacy, when lenalidomide is combined with low-dose dexamethasone (Rd) as compared with lenalidomide in combination with high-dose dexamethasone. This two-drug regimen is of interest for treatment of the elderly, as, conceivably, patients could be maintained on treatment for a longer period of time given the more favorable toxicity profile. However, no direct comparison with the MP-based regimens has been undertaken previously. The IFM2007-01/FIRST study is not only the largest phase III trial conducted in myeloma but is also the first study to compare, head-to-head, two different treatment strategies (i.e., the MP+T, three-drug regimen, versus the Rd, two-drug regimen).
Comment:
Currently, there is no consensus on the optimal upfront treatment of myeloma affecting elderly patients or those who are not candidates for high-dose chemotherapy with autologous stem cell rescue. Three-drug regimens that include MP in combination with either Velcade or an immunomodulatory drug (thalidomide or lenalidomide) are highly efficacious, but treatment is often complicated by debilitating neurotoxicity. Lenalidomide in combination with low-dose decadron (Rd) is an active regimen with a favorable toxicity profile; however, whether Rd is equally (or more or less) efficacious than MP+T is unknown. The current study is designed to compare the two regimens with a goal of illuminating the optimal approach to managing previously untreated myeloma in elderly patients and in those who are not transplant candidates. The fact that the study has already reached its accrual goal means that results will be reported in the near future. Evidenced-based guidance will be welcomed by clinicians who are often challenged by the dilemma of how best to manage this frequently encountered patient category.
