First-line treatment of newly diagnosed multiple myeloma using the Rd regimen (continuous lenalidomide [Revlimid] plus low-dose dexamethasone) was superior to standard triplet treatment with MPT (melphalan, prednisone, and thalidomide [Thalomid]) for 72 weeks, according to initial results of the FIRST (Front-Line Investigation of Revlimid/Dexamethasone vs Standard Thalidomide) trial presented at the 55th Annual Meeting of the American Society of Hematology (ASH) in New Orleans.

Multiple Benefits

Patients treated with Rd were 28% less likely to experience disease progression or death compared with those who received MPT, and Rd improved overall survival, response rates, and duration of response. Additionally, Rd appears to have a safety advantage over MPT by causing fewer secondary hematologic malignancies.

“Traditionally, newly diagnosed multiple myeloma 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 chances for overall long-term survival,” stated lead author Thierry Facon, MD, Services des Maladies du Sang, Hôpital Claude Huriez, and CHRU Lille, France.

“Continuous Rd represents a new standard of care for older transplant-ineligible patients. For some patients with low-risk multiple myeloma, this continuous regimen could make this disease a manageable, chronic condition,” Dr. Facon stated.

Study Details

The multicenter, open-label, phase III trial, conducted at 246 centers in 18 countries, enrolled 1,623 newly diagnosed multiple myeloma patients who were ineligible for stem cell transplant due to older age or other reasons. Median age was 73 (range, 40–92 years), and 35% of patients were aged 75 or older; 41% had stage III disease.

Participants were randomly assigned to one of three arms: continuous Rd in 28-day cycles until disease progression. Rd for 18 cycles (72 weeks), or MPT for 12 cycles (72 weeks). Responses were assessed after each cycle of chemotherapy. Dose adjustments were permitted for adverse events. All patients received antithrombotic prophylaxis as part of the protocol.

At a median follow-up of 37 months, the study met its primary endpoint of progression-free survival comparing continuous Rd vs MPT for 72 weeks, demonstrating a highly significant 28% reduction in risk of disease progression or death (P = .00006). Median progression-free survival was 25.5 months for continuous Rd vs 21.2 months for MPT.

Median progression-free survival was also significantly better for continuous Rd vs Rd for 18 cycles: 25.5 months vs 20.7 months (P = .00001).

Even more important, continuous Rd led to improvement in overall survival (59% at 4 years) vs MPT (51.4% at 4 years). The 4-year median survival rate in patients receiving Rd for 18 cycles was 55.7%.

Continuous Rd achieved consistent improvement over MPT for all secondary endpoints: Overall response rate (partial response or better) was 75% vs 62% (P < .0001), respectively.

Adverse Events

The safety profiles for the two treatment arms (continuous Rd vs MPT) were similar, with numerically fewer hematologic side effects in the doublet arm, as well as fewer hematologic malignancies. In this study, the incidence of secondary solid cancers was identical in both arms (2%), and the incidence of secondary hematologic malignancies was 0.4% with continuous Rd vs 2.2% with MPT.

Relevant grade 3 or 4 adverse events in the continuous Rd arm vs MPT, respectively, were neutropenia (28% vs 45%), thrombocytopenia (8% vs 11%), febrile neutropenia (1% vs 3%), infection (29% vs 17%), neuropathy (5% vs 15%), and deep-vein thrombosis (5% vs 3%). ■

Disclosure: The study was supported by Celgene and the French Francophone Myeloma Intergroup. Dr. Facon is a member of the Board of Directors or advisory committee and the speakers bureau for Celgene.

Reference

1. Facon T, Dimopoulos M, Dispenzieri A, et al: Initial phase 3 results of the FIRST trial in newly diagnosed multiple myeloma patients ineligible for stem cell transplant. 2013 ASH Annual Meeting. Abstract 2. Presented December 8, 2013.