Results from a recent retrospective study conducted in France indicate that long-term treat­ment with Revlimid plus dex­a­meth­a­sone is effective in delaying dis­ease progression in relapsed multiple myeloma patients.

Among patients treated with Revlimid ^[1] (lenalidomide) plus dex­a­meth­a­sone ^[2] (Dec­a­dron) for at least two years, almost all (96 percent) responded to treat­ment, with 74 percent achieving at least a very good partial re­sponse.

Patients who received treat­ment for at least three years were significantly more likely to have not yet progressed 37 months after beginning treat­ment (91 percent), compared to patients who were treated for two to three years (78 percent).

Based on this finding, the researchers state that it is important for patients to continue Revlimid-dex­a­meth­a­sone ther­a­py as long as they are able to tolerate the regimen.

However, nearly half of the patients experienced serious side effects that caused them to lower their dose of Revlimid or to completely stop the regimen.

According to the French researchers, the findings from this study are com­par­able to those from previous studies of Revlimid-plus-dex­a­meth­a­sone ther­a­py in relapsed myeloma, which frequently have found that treat­ment for at least one year results in better outcomes that treat­ment for shorter periods of time (see, for example, this recent Beacon ^[3] article).

Background

Novel drugs such as Revlimid, Velcade ^[4] (bortezomib), and thalidomide ^[5] (Thalomid) have become common treat­ment options for relapsed and refractory myeloma patients.

These drugs have been shown to be able to provide long-term control of myeloma.

The investigators of this study state that the short-term efficacy and safety of Revlimid are well known, but the efficacy and tolerability of long-term exposure to Revlimid-dex­a­meth­a­sone ther­a­py are less well known.

They were therefore interested in assessing the long-term safety and efficacy Revlimid plus dex­a­meth­a­sone ther­a­py, which is approved for the treat­ment of relapsed/refractory myeloma patients who have received at least one prior treat­ment.

Study Design

Researchers from France retrospectively analyzed the records of 50 relapsed myeloma patients who had received combination ther­a­py with Revlimid and dex­a­meth­a­sone. The median age of the patients was 58 years.

Eight percent of the patients had one or both of the chromosomal abnormalities del(17p) and t(4;14), as determined by fluorescence in situ hybridization (FISH).  The presence of these abnormalities is generally considered a sign that a patient's myeloma will be more difficult to treat (see related Beacon ^[6] news article).

Revlimid starting doses ranged from 10 mg to 25 mg daily, and the majority of patients received 40 mg of dex­a­meth­a­sone once a week.

All patients received Revlimid plus dex­a­meth­a­sone for at least two consecutive years, and 56 percent re­ceived Revlimid plus dex­a­meth­a­sone for at least three years.

Half of the patients received the two-drug combination at their first relapse, 38 percent received it at their second relapse, and 12 percent received it later in the course of their disease.  The median time from diag­nosis to start of Revlimid-dex­a­meth­a­sone ther­a­py was 4.5 years.

The median follow-up time was four years.

Results

Overall, 96 percent of the patients responded to Revlimid-dex­a­meth­a­sone ther­a­py, with 74 percent achieving at least a very good partial response.

The median time to first response was two months, and the median time to best response was 4.5 months.

Age, number of previous lines of ther­a­py, starting Revlimid dose, and dose reductions did not appear to sig­nif­i­cantly impact response rates.

The investigators note that the 96 percent overall response rate they observed in their study is higher than what has been seen in other studies of Revlimid+dexamethasone in relapsed myeloma patients.

They believe this may be due, in part, to fewer patients in their study having high-risk chromo­somal ab­nor­mal­i­ties than is usually the case.

Patients who received Revlimid for two to three years achieved deeper responses than those who received it for at least three years (82 percent achieved at least a very good partial response versus 67 percent, re­spec­tive­ly).

However, the percent of patients who had not yet progressed at 37 months was significantly greater in pa­tients who received the combination for at least three years compared to those who received it for two to three years (91 percent versus 78 percent, re­spec­tive­ly).

The median time to progression for all patients was not reached, but the researchers estimated that 52 percent of patients would not yet have progressed four years after starting Revlimid-dex­a­meth­a­sone ther­a­py.

The researchers state that long-term exposure to Revlimid-dex­a­meth­a­sone has an acceptable safety profile.

Overall, 46 percent of the patients developed severe side effects. The most common severe side effects were low white blood cell counts (16 percent), low platelet counts (6 percent), and low red blood cell counts (6 percent).

In addition, 20 percent of patients developed a blood clot in a vein.  This is a higher rate than observed in other studies (see related Beacon ^[7] news article).  The median time till the development of a blood clot was five months.  In all but one case, the patients were receiving treat­ment to prevent blood clots at the time of the clot occurred.

The rate of side effects was similar among those treated with Revlimid for two to three years and those treated for at least three years.

In total, 38 percent of the patients stopped treat­ment, with 18 percent stopping treat­ment due to serious side effects.

In addition, 6 percent of the patients developed a secondary cancer ^[8] at a median time of four years after start­ing Revlimid ther­a­py.  No patients who were treated with Revlimid for more than three years, however, de­vel­oped a sec­ond cancer.

The researchers note that the safety profile of Revlimid+dex­a­meth­a­sone was similar in all patients, re­gard­less of age or number of prior therapies.  They also add that outcomes – including response rates, duration of treat­ment, and time to progression – were similar for patients who did and those who did not ex­per­i­ence serious side effects.

For more information, please refer to the study in the journal Cancer ^[9] (abstract).