New information was released last week regarding long-term treatment with Revlimid and a multiple myeloma patient’s risk of developing a second cancer.

The information is based on analyses prompted by results from three clinical trials presented at the American Society of Hematology meeting last month.  In each of the three trials, more multiple myeloma patients receiving Revlimid maintenance therapy reported developing a secondary cancer than patients who did not receive maintenance therapy.

Celgene, the manufacturer of Revlimid (lenalidomide), announced the results of the follow-up analyses during a quarterly earnings conference call on Thursday.

“While a higher number of second primary malignancies were observed in the Revlimid treatment arms of these controlled studies, a consistent reporting bias existed due to significantly shorter duration of follow-up in the control arms,” said Robert Hugin, Chief Executive Officer of Celgene.

Mr. Hugin explained that in cancer clinical trials, once patients complete the treatment regimen being studied, those patients are only followed for survival.  They are no longer followed for medical conditions such as secondary cancers.  Therefore, the different lengths of follow-up for the maintenance versus placebo arms of the trials can result in a difference in number of reported secondary cancers.

Celgene compared data from four Revlimid clinical trials with results in the U.S. SEER Cancer Registry, the largest source of cancer statistics in the United States.  The four trials analyzed by Celgene were the ones the company sponsored to support its regulatory filings to allow the company to market the drug.

The analysis did not include, however, results from the IFM 2005-02 and CALGB 100104 trials of Revlimid maintenance therapy after stem cell transplantation, and the analysis may only have included older data from the MM-015 trial of Revlimid, melphalan (Alkeran), prednisone plus Revlimid maintenance.  Recent results of the IFM 2005-02, CALGB 100104, and MM-015 trials were what began the concern over Revlimid’s potential link to secondary cancers.

The number of cases of secondary cancer in the four Revlimid regulatory trials analyzed by Celgene was low enough that the company could not detect an increased risk of secondary cancers compared to the national registry.  The analysis was reviewed by independent investigators to verify its methods and conclusions.

A Citigroup analyst report from Thursday states that Celgene believes secondary cancers in Revlimid patients are occurring more heavily in patients also treated with melphalan and prednisone.  The Beacon has not been able to confirm the source of this claim with either Citigroup or Celgene.  Melphalan, like other so-called alkylating agents, is known to increase the risk of secondary cancers.

Celgene additionally reported results of another analysis it carried out using Revlimid safety data.  Like all manufacturers of prescription drugs, Celgene must keep track of all side effect and other safety-related reports it receives regarding the drugs it markets.  Based on these reports and the fact that over 170,000 patients have been treated with Revlimid, Celgene estimates that less than 0.5 percent of Revlimid patients have developed a secondary cancer.

Despite the data suggesting that Revlimid does not cause or increase the risk of secondary cancers, Celgene also announced that the French collaborative group conducting the IFM 2005-02 study is considering amending the trial protocol to discontinue Revlimid maintenance therapy now that patients have been treated for more than two years.

Celgene explained that the IFM investigators would like to begin detailed analyses of subsets of the participants, and that they will also re-treat relapsed participants with additional Revlimid.  It remains unclear, however, why the IFM investigators would choose to discontinue maintenance therapy in the trial unless there is concern over the risk of patients developing secondary cancers.

No changes are currently being made to any other Revlimid clinical trials.

Additional analyses of Revlimid’s potential link to secondary cancers are expected to be published and presented at medical conferences later this year.

For more information, see the transcript from the Celgene conference call and the Beacon’s recent coverage of the Revlimid maintenance studies.