The Myeloma Beacon has learned that the Cancer and Leukemia Group B, the cooperative group running the CALGB / ECOG / BMT-CTN 100104 Revlimid maintenance trial, currently has no plans to halt Revlimid therapy in its trial.
The CALGB trial is one of three trials which released data last December that raised concerns about a potential link between long-term Revlimid (lenalidomide) use and second cases of cancer in multiple myeloma patients.
Among the 231 patients in the Revlimid maintenance arm of the CALGB trial, 15 second cancers have been reported. Among the 229 patients in the placebo (control) arm of the trial, six second cancers have been reported.
Recently, the French “IFM” cooperative group decided to halt the dosing of patients in its Revlimid maintenance trial. Several IFM investigators have reportedly said that this decision was made specifically due to a higher rate of second cancers observed in trial patients who have taken Revlimid for longer than two years (see related Beacon news).
The IFM 2005-02 trial and the international MM-015 trial were the other two studies that reported data in December that sparked concerns about Revlimid and secondary cancers.
In a statement emailed to The Myeloma Beacon, the lead investigator of the CALGB 100104 trial, Dr. Philip McCarthy of the Roswell Park Cancer Institute, made clear that Revlimid dosing will continue in that trial.
Dr. McCarthy said:
“There are no plans to suspend the lenalidomide [Revlimid] maintenance arm of CALGB 100104 at this time. The Cancer Therapy Evaluation Program at the National Cancer Institute is currently reviewing the data relative to second cancers in myeloma and other tumors across the portfolio. Findings from this review will be shared and may be helpful toward developing an informed consensus on this issue. At present, there is not enough data to say conclusively that lenalidomide is associated with an unacceptable increase in the incidence of solid tumors or hematologic malignancies.”
Dr. McCarthy also explained in his statement several reasons why the CALGB is currently hesitant to act on apparent differences in the number of second cancers in the two arms of its trial:
“There could be an observational bias in that patients who are on lenalidomide are followed more often than patients who have progressed. Patients who have progressed may not have cancer screening tests (e.g., Pap smears, colonoscopies, mammograms, etc.) as often as those who are in remission or with stable disease. So far, there does not appear to be an increased number of second cancers in the placebo patients who crossed over to lenalidomide. … It is important to remember that multiple myeloma patients, especially those who have received treatment, are at risk for the development of second cancers, so sorting out what is due to a single drug or combination of drugs is very difficult.”
In addition, Dr. McCarthy noted that “There was a significant benefit in terms of progression-free survival in the lenalidomide [Revlimid] arm and this effect might be lost if the patients prematurely stop taking the drug.”
In his correspondence with The Beacon, Dr. McCarthy likewise shared some perspectives on the recent decision by the IFM group to halt Revlimid dosing in its Revlimid maintenance trial. He explained that he has not seen the IFM data in detail, but he believes it important when considering the IFM decision to bear in mind key differences between the CALGB and IFM trials.
Dr. McCarthy listed, in particular, the following aspects of the IFM trial that were different from the CALGB trial:
- There was a consolidation with Revlimid for two months at about three months post transplant before patients were randomized to placebo or Revlimid.
- About 20 percent of patients received two transplants with melphalan (Alkeran), which is associated with bone marrow disorders.
- The follow up is longer.
- The placebo arm was not given the option of crossing over to Revlimid, unlike CALGB 100104.
- The induction regimens in IFM 2005-02 were very different from CALGB 100104. There were more patients who received Velcade (bortezomib) and non-thalidomide (Thalomid) and non-Revlimid containing regimens when compared to CALGB 100104, where the majority of patients had exposure to thalidomide or Revlimid.
The Beacon has not yet received a response from investigators leading the MM-015 trial regarding their plans for Revlimid dosing in that trial. Representatives from Celgene told The Beacon this past Friday, however, that they have no indication Revlimid dosing will be halted in that trial.