New Orleans, LA—The value of the continued use of lenalidomide (Revlimid) in patients with newly diagnosed multiple myeloma (MM) was highlighted in a phase 3 clinical trial that was featured in a plenary session during ASH 2013.
The Frontline Investigation of Revlimid plus Dexamethasone versus Standard Thalidomide (FIRST) trial was conducted in patients with newly diagnosed MM who were ineligible for stem-cell transplantation and is the largest trial ever conducted in patients with MM.
The key finding of FIRST was that lenalidomide given continuously to newly diagnosed, transplant-ineligible patients prolongs progression-free survival (PFS) and overall survival (OS). The hazard ratio (HR) of 0.72 for PFS, the study’s primary end point, was statistically significant, thus establishing continuous lenalidomide “as a new standard of care,” according to Thierry Facon, MD, of the Centre Hospitalier Régional Universitaire de Lille, France.
Jesús F. San Miguel, MD, PhD, Head of Hematology, Hospital Universitario de Salamanca, Spain, agreed with the investigators. “Continuous lenalidomide plus low-dose dexamethasone demonstrates a significant PFS and OS advantage.” While suggesting that some questions remain to be answered—such as the role of alkylators 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 years) or otherwise ineligible for stem-cell transplant. Unlike many other trials, patients with renal insufficiency were included, making this essentially a “real-life patient population,” Dr Facon noted. The patients were randomized to receive continuous lenalidomide (Rd), to lenalidomide for 72 weeks (Rd18), or to melphalan/prednisone/thalidomide (MPT) for 72 weeks.
Among the study’s main findings are:
- 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 = .006). For Rd versus Rd18, the HR was 0.70 (P = .001)
- The 3-year PFS was 42% with Rd, and 23% in the other 2 arms; the 2 lenalidomide arms were equivalent until month 18, then the curves markedly separated
- A consistent benefit was seen across most subgroups
- Rd was superior to MPT across all efficacy secondary end points
- There were no unexpected toxicities.
The interim analysis for OS, with 35% of patients in the intent-to-treat arms having died, was significantly improved with continuous lenalidomide treatment. At 4 years, 59.4% of patients receiving Rd were alive compared with 51.4% of the MPT arm (HR, 0.78; P = .0168) and 55.7% of the Rd18 arm (P = .307). The time to progression and the time to second antimyeloma therapy were also significantly prolonged with Rd (P = .001 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 patients in the MPT and Rd arms, and in 5.4% of patients in 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,” Dr Facon said.