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Published on 5 September 2014

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Phase III FIRST Trial of REVLIMID® plus dexamethasone published in NEJM

Celgene Corporation announced that data from FIRST (MM-020/IFM 07-01)—an open-label phase III randomised study of continuous REVLIMID (lenalidomide) in combination with dexamethasone in patients newly diagnosed with multiple myeloma (NDMM) who are not candidates for stem cell transplant— have been published in the Sept. 4 issue of the New England Journal of Medicine.

Celgene Corporation announced that data from FIRST (MM-020/IFM 07-01)—an open-label phase III randomised study of continuous REVLIMID (lenalidomide) in combination with dexamethasone in patients newly diagnosed with multiple myeloma (NDMM) who are not candidates for stem cell transplant— have been published in the Sept. 4 issue of the New England Journal of Medicine.

Initial findings, including that the trial had met its primary endpoint of progression free survival (PFS), were reported during the plenary session at the 55th American Society of Hematology annual meeting in December 2013.

The findings, as published in the New England Journal of Medicine, demonstrated that at a median follow-up of 37 months among surviving patients, the median progression-free survival was 25.5 months with continuous oral lenalidomide plus low-dose dexamethasone (Rd), 20.7 months with a fixed course of oral lenalidomide plus low-dose dexamethasone (Rd18) and 21.2 months with melphalan, prednisone and thalidomide (MPT). This resulted in a 28% reduction in risk of progression or death for patients treated with continuous Rd compared with those treated with MPT (HR 0.72; 95% CI, 0.61 to 0.85; P<0.001) and a 30% reduction compared with Rd18 (HR 0.70; 95% CI, 0.60 to 0.82; P<0.001) in the study.

The pre-planned interim analysis of overall survival demonstrated a 22% reduction in risk of death for continuous Rd vs. MPT (HR 0.78; 95% CI, 0.64 to 0.96; P=0.02), although the difference did not cross the pre-specified superiority boundary (P<0.0096). As of the time of the analysis (May 24, 2013), 121 of 535 (23%) patients in the continuous Rd arm were still on therapy.

Additional secondary endpoints showed response rates were also significantly better with continuous Rd (75%) and with Rd18 (73%) than with MPT (62%; P<0.001 for both comparisons). More patients achieved a very good partial response or better in the continuous Rd (44%) or Rd18 arms (43%) compared with MPT (28%). Complete response rates were 15%, 14% and 9% for continuous Rd, Rd18 and MPT, respectively. Median duration of response was 35.0 months with continuous Rd compared with 22.3 months for MPT (HR 0.63; P<0.001) and 22.1 months for Rd18 (HR 0.60; P<0.001). Median time to disease progression was 32.5 months for patients receiving continuous Rd compared with 23.9 months (HR 0.68; P<0.001) for MPT and 21.9 months (HR 0.62; P<0.001) for Rd18.

Safety results showed that grade 3/4 adverse events that occurred in at least 8% of patients in the continuous Rd arm, Rd18 arm or MPT arm included neutropenia (28%, 26%, 45%, respectively), anemia (18%, 16%, 19%), thrombocytopenia (8%, 8%,11%), febrile neutropenia (1%, 3%, 3%), leukopenia (5%, 6%, 10%), infection (29%, 22%, 17%), pneumonia (8%, 8%, 6%), deep-vein thrombosis and/or pulmonary embolism (8%, 6%, 5%), asthenia (8%, 6%, 6%), fatigue (7%, 9%, 6%), and peripheral sensory neuropathy (1%, <1%, 9%).

Rates of grade 3/4 cardiac disorders for patients in the continuous Rd, Rd18 and MPT arms were 12%, 7% and 9%, respectively. The incidence of invasive second primary malignancies was 3% in patients taking continuous Rd, 6% in patients taking Rd18 and 5% in those taking MPT; the overall incidence of solid tumors was identical in the continuous Rd and MPT arms (3%) and 5% in the Rd18 arm.
For additional results from the publication, visit http://www.nejm.org/

Based on the results of the FIRST study, Celgene submitted REVLIMID in combination with dexamethasone for the treatment of newly diagnosed multiple myeloma patients with the European Medicines Agency (EMA) in February 2014 and with the U.S. Food and Drug Administration (FDA) in April 2014.

These results are from an investigational study. REVLIMID is not indicated for use in newly diagnosed multiple myeloma patients in any country.



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