Data from the FIRST (Frontline Investigation of lenalidomide and dexamethasone vs. standard thalidomide) trial have been published in The New England Journal of Medicine (NEJM). 

This follows the presentation of initial findings at the 55th American Society of Hematology annual meeting in December 2013.

FIRST (MM-020/IFM 07-01), a phase III, multi-centre study of 1,623 patients newly diagnosed with multiple myeloma (NDMM) and ineligible for stem cell transplant,3 included 72 patients from the UK.

After a median follow-up of 37 months, the trial met its primary endpoint (progression-free survival), demonstrating a 28% reduction in the risk of progression or death for patients treated with continuous lenalidomide plus low-dose dexamethasone (LEN LoDex) compared with those receiving melphalan, prednisone and thalidomide (MPT) for 72 weeks, the standard of care (HR 0.72; 95% CI, 0.61 to 0.85; P<0.001).

Median PFS was 25.5 months for patients receiving continuous LEN LoDex vs. 21.2 months for those receiving MPT.

In addition, the pre-planned interim analysis of overall survival demonstrated a 22% reduction in the risk of death in favour of patients receiving continuous LEN LoDex vs. patients receiving 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).

All other secondary endpoints, including response rates, time to disease progression and time to treatment failure, consistently showed improvement for patients receiving continuous LEN LoDex compared with those receiving MPT.

Safety results from the FIRST trial showed that grade 3/4 adverse events in patients taking continuous LEN LoDex vs. those taking MPT included neutropenia (28% vs. 45%), anaemia (18% vs. 19%), thrombocytopenia (8% vs. 11%), febrile neutropenia (1% vs. 3%), leukopenia (5% vs. 10%), infection (29% vs. 17%), pneumonia (8% vs. 6%), neuropathy (1% vs. 9%), asthenia (8% vs. 6%), fatigue (7% vs. 6%), peripheral sensory neuropathy (1% vs.9%) and deep-vein thrombosis and/or pulmonary embolism (8% vs. 5%).

The incidence of invasive secondary primary malignancies was 3% in patients taking continuous LEN LoDex vs. 5% in those taking MPT; the overall incidence of solid tumours was similar (3%).

Commenting on the publication in the NEJM, Dr Adrian Kilcoyne, Medical Director, Celgene UK & Ireland said; “While multiple myeloma is a debilitating and incurable disease, results from the FIRST study indicate that continuous treatment with lenalidomide may be able to keep newly diagnosed patients in remission for longer than with the current standard of care. This is encouraging as lengthy remission is an important goal for patients and is associated with a good prognosis.”

Lenalidomide is not currently licensed for NDMM in the UK or any other countries. 

However, data from the FIRST study have been used to support a filing to the European Medicines Agency (EMA) for the use of lenalidomide as a potential treatment for NDMM.

References

Facon T 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). American Society Hematology (ASH) Poster. December 2013. 

Source: Calgene