The results of a Phase III trial of a combination using Celgene Corp's Revlimid will change clinical practice for patients with multiple myeloma, experts have said.

The 1,623-patient FIRST trial, presented at the American Society of Hematology conference in New Orleans last week, is the largest to compare a combination of Revlimid (lenalidomide) and dexamethasone with standard therapy of melphalan, prednisone and thalidomide (MPT). Patients who were either older than 65 or otherwise ineligible for a stem-cell transplant were randomised to one of three trial arms: RD in 28-day cycles until disease progression, RD in 28-day cycles for 72 weeks or MPT in 42-day cycles for 72 weeks.

After a median follow-up of 37 months the trial met its primary endpoint, with RD demonstrating a 28% reduction in the risk of progression or death. An interim analysis of one of the secondary endpoints, overall survival, found a non-significant 22% reduction in the risk of death in favour of RD compared with MPT. All other secondary endpoints – overall response rate, time to response, duration of response, safety and quality of life – showed improvements in favour of RD.

Lead researcher Thierry Facon of the Claude Huriez hospital in Lille, France, said the data “establishes the RD combination treatment as a new standard of care". Speaking at an ASH plenary session, Dr Facon said: “Continuous treatment with all-oral RD significantly improved the primary endpoint of progression-free survival compared with the standard triplet". He added that "the safety profile of RD was manageable, with reduced haematologic secondary primary malignancies compared to MPT".

Gareth Morgan, head of the myeloma unit at the Royal Marsden hospital in London, said the results of FIRST supported early indications from his own research with RD and cyclophosphamide, which suggested that “continuing Revlimid until disease progression is a very good way to use the drug. It’s a really very interesting and important study that really could change practice. I imagine it would form part of a submission package to the EU regulatory authorities".

'Massive' PFS difference

He added that "there was a massive progression-free survival difference, and what looked like a survival benefit for RD until progression, which didn’t reach statistical significance after 37 months but we would expect it to over a longer time. On this occasion we can say that this is possibly a paradigm shift in myeloma treatment.”
The RD combination is not licensed in Europe for first-line treatment, but has been recommended by NICE for secondary relapses. Novel therapies developed for multiple myeloma have nearly doubled five-year survival of the blood cancer from 31% to 56% between 2006 and 2010.

Prof Morgan argued that "for regulators this would be a step forward, moving it from relapse to an upfront treatment – that was part of the excitement [at ASH]. Myeloma is generally seen as a disease of the elderly that is incurable and this could change its perception.

This combination "could create a whole new approach in the UK", he added, saying that "this is an option for elderly people who would otherwise be very sick and would die very quickly". Maria-Victoria Mateos of the University of Salamanca, Spain, echoed this stance, claiming that the data "clearly supports a new standard of care for patients and also a new backbone against which other drugs can be tested".