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Lenalidomide plus dexamethasone prolonged PFS in multiple myeloma

Patients with newly diagnosed multiple myeloma treated with the immunomodulatory drug lenalidomide plus low-dose dexamethasone experienced significantly longer PFS compared with those treated with the standard regimen of melphalan, prednisone and thalidomide, according to results of a randomized, open-label, phase 3 study.

“At the present time, especially in the EU but also in many other countries, melphalan-prednisone in combination with thalidomide is the preferred regimen … for patients with newly diagnosed myeloma ineligible for stem cell transplantation,” lead study author Thierry Facon, MD, of the Hôpital Claude Huriez in Lille, France, said during a press conference. “However, this treatment has been based on fixed duration, mainly due to toxicities associated with long-term duration.”

The study included 1,623 patients with newly diagnosed multiple myeloma who either were aged 65 years or older or ineligible to undergo stem cell transplantation. The median age of patients was 73 years (range, 40-92), and 35% of patients were aged 75 years or older.

Forty-one percent of patients had stage III disease.

Facon and colleagues randomly assigned patients to one of three treatment regimens: lenalidomide (Revlimid, Celgene) plus low-dose dexamethasone in 28-day cycles until disease progression (Arm A); lenalidomide plus low-dose dexamethasone in 28-day cycles for 72 weeks (Arm B); or melphalan (Alkeran, GlaxoSmithKline), prednisone and thalidomide (Thalomid, Celgene) in 42-day cycles for 72 weeks (Arm C).

The starting dose of lenalidomide was adjusted for renal function and the starting dose of dexamethasone was adjusted for age. The starting dose of melphalan was adjusted for age, absolute neutrophil count, platelet count and renal function, and the starting dose of thalidomide was adjusted for age. All patients received anti-thrombotic prophylaxis.

A PFS comparison between Arm A and Arm C served as the primary endpoint. OS, overall response rate, time to response, duration of response, safety and quality of life in those two treatment arms served as secondary endpoints.

Median follow-up was 37 months. At that time, researchers noted the primary outcome was met, as they calculated a 28% reduction in risk for disease progression or death among patients assigned to lenalidomide plus dexamethasone compared with those assigned to the melphalan combination (HR=0.72; P=.00006).

Patients assigned to lenalidomide plus dexamethasone demonstrated superior OS. Researchers reported a 22% reduction in death among patients assigned to that regimen compared with those assigned to the melphalan combination (HR=0.78; P=.01685).

Patients in the lenalidomide plus dexamethasone group also demonstrated superior overall response rate (75% vs. 62%; P<.00001), duration of response (HR=0.63; P<.00001), and time from randomization to second progression event or death (HR=0.78; P=.0051).

Patients assigned to the melphalan combination experienced higher rates of grade 3 or grade 4 neutropenia (45% vs. 28%), thrombocytopenia (11% vs. 8%), febrile neutropenia (3% vs. 1%) and neuropathy (15% vs. 5%). Patients assigned to lenalidomide and dexamethasone experienced higher rates of infection (29% vs. 17%) and deep vein thrombosis (5% vs. 3%).

Incidence of secondary hematologic malignancies was higher in the melphalan arm (2.2% vs. 0.4%). Incidence of secondary solid tumors was 2.8% in both arms.

“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,” Facon said in a press release. “For some patients with low-risk myeloma, this continuous regimen could make this disease a manageable, chronic condition.”

Reference:

Facon T. Abstract #2.

Disclosure:

The researchers report employment, board membership, advisory, speakers’ bureau, lecture and consultant roles with, honoraria, research funding, patents and royalties from, and equity ownership in Acetylon, Aventis, Bristol-Myers Squibb, Celgene, Gilead, GlaxoSmithKline, Janssen, Johnson & Johnson, Lundbeck, Millennium, Mundipharma, OncoPep, Onyx, Orthobiotech, Pfizer, Roche and Sanofi.