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FDA Approves Frontline Revlimid for Multiple Myeloma

Jason M. Broderick @jasoncology
Published: Wednesday, Feb 18, 2015

Kenneth C. Anderson, MD

Kenneth C. Anderson, MD

The FDA has approved lenalidomide (Revlimid) plus dexamethasone in newly diagnosed patients with multiple myeloma based on findings from the phase III FIRST trial.

In the open-label phase III study, treatment with continuous lenalidomide plus low-dose dexamethasone reduced the risk of disease progression by 28% compared with the MPT regimen of melphalan, prednisone, and thalidomide. Median progression-free (PFS) survival was improved by 4.3 months with continuous lenalidomide/dexamethasone versus MPT (HR = 0.72; 95% CI, 0.61-0.85; P = .0001).

"The approval of Revlimid as an option for use in all patients with multiple myeloma represents a new paradigm in the management of this disease,” said Kenneth Anderson, MD, director, Jerome Lipper Multiple Myeloma Center, Dana-Farber/Brigham and Women’s Cancer Center. “We now have clinical evidence demonstrating that starting and keeping newly diagnosed multiple myeloma patients on Revlimid significantly improves progression-free survival."

The international, three-arm FIRST trial randomized 1623 patients in a 1:1:1 ratio to continuous lenalidomide/dexamethasone until disease progression (n = 535), eighteen cycles of lenalidomide/dexamethasone (72 weeks; n = 541), or twelve cycles of MPT (72 weeks; n = 547). Treatment cycles were 28 days.

For the lenalidomide arms, patients received the drug at 25 mg daily on days 1 to 21 of each cycle and 40 mg of dexamethasone daily on days 1, 8, 15, and 22. MPT was administered at 0.25 mg/kg of melphalan and 2 mg/kg of prednisone on days 1 to 4 of each cycle, along with 200 mg of thalidomide daily throughout the cycle.

Median patient age in all three arms was 73 years. Patients were stratified by age, disease stage, and country. The primary endpoint was PFS with continuous lenalidomide versus MPT. Secondary end points included overall survival (OS), overall response rate (ORR), time to response, duration of response, and safety.

PFS was 25.5 months with continuous lenalidomide, 20.7 months with the fixed lenalidomide regimen, and 21.2 months with MPT. Compared with the MPT and fixed-course arms, continuous lenalidomide led to a 28% and 30% reduction, respectively, in the risk of disease progression or death.

Based on a March 3, 2014, interim OS analysis, continuous lenalidomide reduced the risk of death by 25% compared with the control arm (58.9 vs 48.5 months; HR = 0.75; 95% CI, 0.62-0.90).

ORR was 75% with continuous lenalidomide versus 62% with MPT (P <.001). Complete response rates were 15% and 9% in the two arms, respectively, and median treatment duration was 18.4 months versus 15.4 months. 

The OS and PFS benefits for continuous lenalidomide versus MPT were consistent in most subgroups, including younger patients and patients aged ≥75 years. The authors did note that the benefit of continuous treatment was not as clear in individuals with a poor prognostic outlook.

The most common adverse events (AEs) in the continuous lenalidomide arm compared with the MPT arm were diarrhea (45.5% vs 16.5%), anemia (43.8%, vs 42.3%), neutropenia (35.0% vs 60.6%), fatigue (32.5% vs 28.5%), back pain (32.0% vs 21.4%), insomnia (27.6% vs 9.8%), asthenia (28.2% vs 22.9%), rash (26.1% vs 19.4%), decreased appetite (23.1% vs 13.3%), cough (22.7% vs 12.6%), pyrexia (21.4% vs 14.0%), muscle spasms (20.5% vs 11.3%) and abdominal pain (20.5% vs 11.1%).

Grade 3 /4 AEs most frequently reported in the continuous lenalidomide arm included neutropenia (27.8%), anemia (18.2%), thrombocytopenia (8.3%), pneumonia (11.3%), asthenia (7.7%), fatigue (7.3%), back pain (7%), hypokalemia (6.6%), rash (7.3%), cataract (5.8%), dyspnea (5.6%), DVT (5.6%), and hyperglycemia (5.3%).

Revlimid was previously approved for use in combination with dexamethasone for patients with multiple myeloma following one prior therapy. The drug also has approved indications for mantle cell lymphoma and myelodysplastic syndromes.

“At Celgene, we are very happy with the FDA’s decision, which adds information on the use of Revlimid plus dexamethasone as a first-line treatment for multiple myeloma to the prescribing information,” said Jacqualyn A. Fouse, PhD, president, Global Hematology and Oncology for Celgene, in a statement. “Now, as part of our commitment to improving the lives of patients living with this disease, our next step is to make the benefits of this treatment regimen available to those now eligible under the expanded indication."


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