February 2014, Vol 3, No 1
FIRST Trial Shows Value of Continued Use of Lenalidomide in Newly Diagnosed Myeloma Patients
The value of the continued use of lenalidomide in patients with newly diagnosed multiple myeloma was front and center among more than 800 abstracts on multiple myeloma presented at ASH.
Featured in a Plenary Session were results from the phase 3 FIRST trial (Frontline Investigation of Revlimid + Dexamethasone Versus Standard Thalidomide) in newly diagnosed multiple myeloma patients ineligible for stem cell transplantation. FIRST is the largest trial ever conducted in multiple myeloma.
The key finding of FIRST was that lenalidomide given continuously to newly diagnosed, transplant-ineligible patients prolongs both progression-free survival (PFS) and overall survival (OS). The hazard ratio (HR) of 0.72 for PFS, the study’s primary end point, was highly statistically significant, thus establishing continuous lenalidomide “as a new standard of care,” according to Thierry Facon, MD, of the Hôpital Claude Huriez and CHRU Lille in Lille, France.
Discussing the study was Jesús F. San Miguel, MD, PhD, professor of medicine and head of hematology at the Hospital Universitario de Salamanca, Salamanca, Spain, who agreed with the investigators.
“Continuous lenalidomide plus low-dose dexamethasone demonstrates a significant PFS and OS advantage,” San Miguel noted. While suggesting that some questions remain to be answered – such as the role of alkylators (ie, melphalan) in light of these findings, and the identification of the population most likely to benefit from this approach – he commented, “Overall, we have a new standard of care that is active, convenient, and has excellent tolerability.”
The study enrolled 1623 patients, aged ?65 years (median age 73) or otherwise ineligible for stem cell transplant. Unlike many other trials, patients with renal insufficiency were allowed, making this essentially a “real-life patient population,” Facon noted.
Patients were randomly assigned to receive continuous lenalidomide (Rd), lenalidomide for 72 weeks (Rd18), or melphalan/prednisone/thalidomide (MPT) for 72 weeks.
Among the study’s main findings were:
- Median PFS, the primary end point, was 25.5 months with Rd, 20.7 months with Rd18, and 21.2 months with MPT. The HR for the primary comparison (Rd vs MPT) was 0.72 (P=.00006). For Rd versus Rd18, the HR was 0.70 (P=.00001)
- 3-year PFS was 42% with Rd and 23% in the other arms; the 2 lenalidomide arms were equivalent until month 18, when the curves markedly separated
- A consistent benefit was seen across most subgroups
- Rd was superior to MPT across all secondary efficacy end points
- There were no unexpected toxicities
The interim analysis for OS, with 35% of the intent-to-treat arms having died, was significantly improved with continuous lenalidomide treatment. At 4 years, 59.4% of Rd patients were alive, compared with 51.4% on the MPT arm (HR 0.78; P=.0168) and 55.7% on the Rd18 arm (P=.307). The time to progression and time to second antimyeloma therapy were also significantly prolonged with Rd (P=.00001 for both).
The rate of secondary hematologic malignancies was low overall but was actually higher in the MPT arm, with 12 patients (2.2%) developing hematologic malignancies compared with 2 patients (0.4%) in each lenalidomide arm. Solid tumors developed in 2.8% of both the MPT and Rd arms and in 5.4% of the Rd18 arm.
“In the relapse setting, len/low-dose dex has been shown very safe in terms of second malignancies, and this trial confirms it is also safe in the first-line setting,” Facon said.
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