Continuous treatment with lenalidomide and low-dose dexamethasone (Rd) was superior to standard treatment with melphalan, prednisone, and thalidomide (MPT) for 72 weeks in newly diagnosed patients with multiple myeloma (MM) who were transplant ineligible. Experts said that these results represented a new standard of care for these patients.
Patients treated with Rd were 28% less likely to progress or die compared with those patients who received standard MPT (the primary end point of the trial). Rd was superior to MPT for all secondary end points, including overall survival, response rates, and duration of response. Patients treated with Rd had fewer secondary hematologic malignancies than those patients in the MPT arm.
“Traditionally, newly diagnosed MM patients have received short bursts of treatment, while continuous treatment was reserved for relapsed patients. However, we believe that these new results will help encourage more research on the efficacy and safety of continuous treatment for newly diagnosed patients to help maximize their changes for overall long-term survival,” stated lead author Thierry Facon, MD, Service des Maladies du Sang, Hôpital Claude Huriez, and CHRU Lille, France, at the American Society of Hematology annual meeting.
“For some patients with low-risk MM, this continuous regimen could make this disease a manageable, chronic condition,” he stated.
The multicenter, phase 3 FIRST (Frontline Investigation of Lenalidomide + Dexamethasone Versus Standard Thalidomide) trial enrolled 1623 newly diagnosed patients with MM who were ineligible for stem cell transplant because of older age (>65 years) or other factors such as comorbidities.
Participants were randomized to 1 of 3 arms:
- Continuous Rd in 28-day cycles until disease progression,
- Rd for 18 cycles (72 weeks), or
- 12 cycles of MPT (72 weeks).
Antithrombotic prophylaxis was included in the protocol. Doses of antimyeloma drugs were adjusted for adverse events.
At a median follow-up of 37 months, the primary end point of progression-free survival (PFS) was reached, with a highly significant 28% reduction in risk of disease progression or death for those treated with Rd versus MPT (P = .00006). Median PFS was 25.5 months for continuous Rd compared with 21.2 months for MPT.
Median survival was also significantly better for continuous Rd than for Rd for 18 cycles: 25.5 months versus 20.7 months (P = .00001).
Four-year overall survival was 59% with Rd compared with 51.4% for MPT; 4-year survival in patients receiving Rd for 18 cycles was 55.7%.
Adverse events were similar in both arms, with the exception of less myelosuppression and fewer secondary hematologic malignancies in the Rd arm.
Reference
Facon T, Dimopoulos MA, Dispenzieri A, et al. Initial phase 3 results of the First (Frontline Investigation of Lenalidomide + Dexamethasone Versus Standard Thalidomide) trial (MM-020/IFM 07 01) in newly diagnosed multiple myeloma (NDMM) patients (Pts) ineligible for stem cell transplantation (SCT). Presented at: 2013 American Society of Hematology Annual Meeting; December 8, 2013; New Orleans, LA. Abstract 2.