Revlimid is the immunomodulatory drug CC-5013, which is a thalidomide (Thalomid®) analog. Revlimid has been in the news for 3 to 4 years. It appears to have anti-myeloma activity that is similar to that of thalidomide, but with a different toxicity profile. On the one hand, Revlimid rarely causes the neuropathy that has been of such concern with chronic thalidomide use. On the other hand, it does cause reduction in blood count values, especially the white blood count and platelet levels.
In 2001 and 2002, phase I-II trials from the Dana-Farber Cancer Institute in Boston, MA, and the University of Arkansas in Little Rock, AR, indicated responses in patients refractory to (failing on) prior therapies, sometimes including thalidomide. As summarized in Table 1, 22% of patients had at least a 50% reduction in myeloma protein levels (partial response [PR]), and 31% of patients reached PR when dexamethasone was combined with the Revlimid. The various side effects are noted.
These promising results led to two large phase III double-blind trials, one in North America and the other in Europe, to compare Revlimid plus dexamethasone versus dexamethasone alone (with placebo instead of Revlimid). Results of these trials were presented earlier this year at the International Myeloma Workshop in Australia, at the ASCO meeting in Florida, and at the EHA meeting in Sweden. The data from the North American trial are summarized in Table 2.
Both the response rate of 61.2% and the length of response of 15 months were significantly larger for Revlimid plus dexamethasone versus dexamethasone alone. Side effects with DVTs (deep vein thromboses) were higher with the combination (15% versus 5%). Daily baby aspirin use is now recommended along with Revlimid.
It is these very encouraging results, combined with the almost exactly duplicated study results from Europe, which have led to the expectation of approval of Revlimid for myeloma by the FDA, in some fashion. However, there are two very important nuances concerning the antici-pated availability of Revlimid:
1. Revlimid FDA Approval Anticipated
- Data supporting the use of Revlimid in another blood cancer called MDS (Myelodysplastic Syndrome), a type of preleukemia, which sometimes has a 5q- chromo-some abnormality, were submitted to the FDA earlier this year. This submission will receive expedited review, which means that a decision will be received from the FDA within 6 months, by Fall of 2005 at the latest.
- If there is approval for Revlimid use in MDS, this means that Revlimid will become commercially available. Myeloma would then become an “off-label” indication. Revlimid most likely could be made available to myeloma patients at the discretion of the treating phy-sician. The major concern would become how exactly reimbursement is handled.
- The combination of Revlimid plus dexamethasone, the successful treatment in the trials summarized in Table 2, will most likely also be submitted to the FDA for review. At this point, the earliest that any specific approval might be received for myeloma is sometime in 2006.
2. Expanded Access Program (EAP)
In the interim, the Celgene Corporation plans to activate an Expanded Access Program (EAP) for Revlimid in mul-tiple myeloma. It is proposed that this be a multi-center, single-arm, open label trial for Revlimid plus dexametha-sone (as used in the recent trials) for previously treated myeloma patients (at least 2 prior cycles of anti-myeloma therapy). Eligible patients will have relapsed or refractory myeloma. Prior use of thalidomide is allowed. Patients will continue on therapy unless myeloma progression occurs and/or Revlimid becomes commercially available. This, therefore, cycles back to item 1 above. Thus, one way or another, it seems that the long wait for Revlimid may be nearing an end. Hopefully, very soon this drug will be in the hands of patients requiring treatment. The IMF will be tracking developments concerning activa-tion of EAP and/or commercial availability of Revlimid. For further information, please call 800-452-CURE (2873).