Revlimid slows multiple myeloma relapse
Multiple myeloma patients in remission after initial therapy can prolong the time to relapse through lenalidomide (Revlimid) maintenance treatment (an immune modulator).
A meta-analysis of trials evaluating the approach confirms that lenalidomide maintenance reduces the risk of relapse by about half, according to Preet Paul Singh, MD, of the Mayo Clinic in Rochester, Minn.
But the drug is associated with a higher risk of adverse events compared with placebo or no maintenance, Singh reported at the annual meeting of the American Society of Hematology.
Importantly, the analysis did not show that the delay in relapse led to longer overall survival.
In the four randomized trials he and colleagues looked at, the primary endpoint was progression-free survival, and in all cases, the drug did extend the time before the disease recurred.
"Lenalidomide maintenance did delay progression," Singh said, although the drug is not approved for maintenance therapy in multiple myeloma.
In fact, the meta-analysis found that the hazard ratio for recurrence was 0.49 (95% CI 0.42-0.56, P<0.001.)
The big question, he said, is: "Are these patients living longer because they're getting this maintenance therapy?"
And that question remains up in the air, Singh said. The meta-analysis found that the hazard ratio for survival was 0.76, but the confidence interval crossed unity, meaning the apparent benefit could be the result of chance.
He cautioned that there was "significant heterogeneity" across the studies for the overall survival estimates, although there was none for progression-free survival.
On the other hand, lenalidomide maintenance was clearly associated with an increased risk of grades 3 and 4 adverse events, he said.
For example, compared with placebo or no maintenance, the risk of neutropenia was nearly five times higher, with an odds ratio of 4.9 that was significant at P<0.001.
The risks of thrombocytopenia, fatigue, and venous thromboembolism were also increased, although to lesser degrees.
There has also been concern about the risk of secondary primary malignancies with lenalidomide and the meta-analysis pinned that down, Singh said.
Compared with no maintenance or placebo, the hazard ratio for a second cancer was 1.62 (95% CI 1.15-2.29, P=0.006.)
More data might help to resolve the issue, commented Xavier Leleu, MD, PhD, of the Claude Huriez Hospital in Lille, France, who was not involved in the study but who moderated the session at which it was presented.
But it's more likely that there are some subgroups of patients who will have a survival benefit and others who will not.
"It's not black and white," he said.
What additional study and more mature data might do, he said, is help to tease out which patients are likely to live longer as a result of lenalidomide maintenance.
Source: MedPage Today: http://www.medpagetoday.com/MeetingCoverage/ASHHematology/43355