A group of mainly European multiple myeloma researchers has issued a statement regarding the potential link between Revlimid and secondary cancer.

According to the statement, the group initially met in Paris on February 23, 2011 at a meeting arranged by Celgene, the company that developed and markets Revlimid (lenalidomide).

The group includes 12 well-known multiple myeloma researchers, almost entirely from Europe. Among the group's members are investigators from the CALGB 100104, IFM 2005-02, and MM-015 clinical trials, which are the three trials that last December reported data suggesting a possible connection between Revlimid and increased rates of secondary cancer.

The group, it should be noted, is not an existing "consensus group" or "working group" of multiple myeloma researchers such as The International Myeloma Working Group.  Instead, it is an ad hoc group arranged by Celgene specifically to review and discuss the Revlimid-secondary cancer issue.

The group's statement is reproduced in full below.  The Myeloma Beacon will have further information on the statement in a more detailed news article later today or over the weekend.

The researchers' statement first appeared online at the website of the British charity Myeloma UK.

Statement of the Multiple Myeloma Researchers

An Advisory Board arranged by Celgene was held in Paris on 23rd February and a consensus view of European myeloma physicians, on the current position of the description and further investigation of second primary malignancies (SPM) after exposure to Lenalidomide, was reached.

1. It was noted that in order to interpret the meaning of an increased rate of SPM, that it is of crucial importance to distinguish clearly between relapsed/refractory multiple myeloma (RRMM) and newly diagnosed multiple myeloma (NDMM).  This distinction is important because of the nature of the prior treatment received, the age of the patient and the nature and duration of follow up in the study.
    
2. There was consensus that there is no apparent increased rate of SPM for patients treated with Lenalidomide/Dexamethasone in RRMM, the current licenced indication for Lenalidomide.  In a review of 11 Celgene-sponsored trials with Lenalidomide/Dexamethasone in relapse/refractory patients, 8.2% of the patients (311 cases) received treatment for >24m, and the incidence of SPM was not increased in this long-term-exposed population. In RRMM there is a clinically significant survival benefit for the use of Lenalidomide.
    
3. There was consensus that there is no apparent increased rate of SPM for NDMM patients treated with Lenalidomide/Dexamethasone, who have not had concurrent or prior exposure to chemotherapy.  For NDMM, there are 3 trials that have used Lenalidomide, in protocols, where there is concurrent or prior use of chemotherapeutic agents, which have reported data, MM-015, IFM-2005-02 and CALGB-100104.  There were apparent increased rates of SPM cases in each of these studies.  A fourth study, MM020, has yet to report.
    
   It is known that there are increased rates of SPM following exposure to DNA damaging chemotherapies.  Thus, it is important to distinguish clearly between the different clinical settings in these NDMM studies where the patients are of different ages, exposed to different induction chemotherapies and have different durations of exposure to Lenalidomide.
    
   Recognising that Lenalidomide as a maintenance treatment in the IFM-2005-02 study has been discontinued.  There was consensus that the MM-015 & MM-020 in NDMM and other co-operative studies in NDMM can continue to completion based on current available data, with appropriate amendments to retrospectively and prospectively capture SPM data.
    
   In the 3 NDMM trials that have reported, there is a highly significant increase in progression free survival (PFS), compatible with an approximate 50-60% decrease in the hazard ratio of disease progression.  This is likely to be of clinical significance, but as yet, has not been associated with an overall survival (OS) benefit.
    
   There was consensus that it would be interesting to see Event Free Survival analyses for IFM-2005-02 & CALGB 100104, where SPM is included as an event (in addition to progression or death), similar to the analysis already conducted for MM-015, in order to further characterize the risk/benefit profile for the agent in these settings.
    
   There was consensus that no additional actions were required by Celgene with regard to ongoing MM-015 and MM-020 studies, above those currently being taken in response to Afssaps (France) Clinical Trial Unit request.
    
4. There was consensus that there is no apparent increased rate of SPM for patients treated with Lenalidomide in Chronic Lymphocytic Leukaemia, lymphomas or solid tumour studies.
    
5. There is a consensus, that going forward there is a need for caution and close follow-up of trials incorporating Lenalidomide.  Until there is more follow up data available Lenalidomide should be used in defined clinical indications and in trials with ongoing data collection on rates of SPM.

Group Members: Michel Attal (France), Michele Cavo (Italy), Bertrand Coiffier (France), Faith Davies (UK), Meletios A. Dimopoulos (Greece), Thierry Facon (France), Heinz Ludwig (Austria), Phillip McCarthy (USA), Gareth Morgan (UK), Jesus F. San Miguel (Spain), Antonio Palumbo (Italy), Pieter Sonneveld (Netherlands).