Last Thursday, the third day of the International Myeloma Workshop (IMW) in Paris, included numerous presentation sessions throughout the day.

The key session during the second part of Day 3, which concerned Revlimid and secondary cancers, is summarized in this article.  Highlights from the first part of Day 3 are summarized in a separate article (see related Beacon news).

Secondary Cancers

The most important session of the afternoon included talks from the lead investigators of the three Revlimid (lenalidomide) maintenance trials that reported increased rates of secondary cancer at the American Society of Hematology annual meeting this past December (see related Beacon news).  Their presentations were then followed by talks that further analyzed the safety of Revlimid as well as a panel discussion on the topic.

The first presentation was by Dr. Michel Attal from the Hopital Purpan in Toulouse, France, and lead investigator of the IFM 2005-02 trial.  In this trial, 614 multiple myeloma patients under the age of 65 years who had recently undergone stem cell transplantation received consolidation therapy with Revlimid and then were randomized to receive Revlimid maintenance therapy or placebo.

Revlimid dosing was stopped in January due to a concern over the number of participants in the Revlimid arm who had developed a second cancer (see related Beacon news).

The results as of April 1 showed Revlimid maintenance therapy reduced the risk of progression by 50 percent.  However, overall survival was similar for both groups, without a trend toward a survival benefit.

An analysis showed that after 24 months, a noticeably increasing share of patients in the Revlimid arm developed a second cancer compared to rate of second cancer in the placebo arm.  Dr. Attal and his colleagues found several factors that were correlated with a higher likelihood of developing a second cancer: treatment with the combination therapy dexamethasone (Decadron)-cyclophosphamide (Cytoxan)-etoposide-cisplatin (known as DCEP) as well as age and gender.  These factors, however, do not account entirely for the differences in second cancer rates between the two maintenance arms of the trial.

Next, Dr. Philip McCarthy from Roswell Park Cancer Center presented updated results from the CALGB trial.  In this trial, 568 myeloma patients under the age of 70 years were randomized to receive either Revlimid maintenance therapy or a placebo following stem cell transplantation.

The results showed, similar to the IFM trial, that Revlimid reduced the risk of progression by 62 percent.  However, the CALGB study is the first to show Revlimid maintenance may have a significant survival benefit.  After 28 months of follow-up time, 90 percent of patients in the Revlimid arm were still alive compared to 83 percent of patients in the placebo group, and this difference is statistically significant.

Dr. McCarthy's update on the results of the trial also revealed, however, a widening in the difference of secondary cancer rates between the Revlimid and placebo arms of the trial.  The latest data analyses by the trial investigators show that 8.65% of the Revlimid maintenance patients have developed a second cancer, compared to 2.03% of placebo patients.

Results from the third Revlimid maintenance study, MM-015, were presented by Dr. Antonio Palumbo of the University of Turin, Italy.  In this trial, 459 patients ages 65 years and older received one of three treatment regimens: melphalan (Alkeran) and prednisone (known as MP) followed by placebo; melphalan, prednisone, and Revlimid (MPR) followed by placebo; or MPR followed by Revlimid maintenance therapy (MPR-R).

Like both of the other studies, Revlimid maintenance the reduced risk of progression by 60 percent.  However, no statistically significant survival benefit is yet present.

Updated safety data showed 8 percent of patients in the MPR-R arm developed a second cancer, 5.9 percent in the MPR arm, and 2.6 percent in the MP arm.  Given that Revlimid delays progression and may extend survival, meaning that patients on Revlimid are treated longer, Dr. Palumbo analyzed the data to take into account the length of time on therapy.  However, the risk of developing cancer in a given year was still higher for the Revlimid arms.

In separate analyses, Dr. Palumbo and Dr. Gareth Morgan from the Royal Marsden Hospital in London both then looked at the rates of second cancers among patients who have been treated with Revlimid compared to the rates among various populations of healthy people.  Both found that on a yearly basis, fewer patients who took Revlimid developed a second cancer than what would be expected based on healthy populations.

After the presentations were complete, the panel of presenters was first asked, “Does Revlimid increase second cancer rates?”  Dr. McCarthy and Dr. Ola Landgren from the National Cancer Institute and National Institutes of Health were both uncertain.  Drs. Morgan and Attal said there may be risk in stem cell transplant patients.  Dr. Palumbo felt that the benefit was much greater than the risk.

The panel was then asked, “Should Revlimid maintenance be stopped at some point?”  Drs. Palumbo and McCarty said no, and Dr. Morgan tended to agree.  Dr. Attal felt longer follow-up was necessary in order to make a recommendation.

For more detailed summaries of the day’s sessions, see The Myeloma Beacon’s extensive Day 3 coverage in the Beacon forums, which includes more extensive coverage of the session on Revlimid maintenance.  For links to abstracts of some of the presentations given during the day, see the IMW programme.  News from the final day of the workshop will also be summarized in a daily update like this one.