The National Comprehensive Cancer Network (NCCN) has updated its guide­lines for the treat­ment of multiple myeloma, and the new guidelines will be interpreted by many as a vote of confidence for Revlimid main­te­nance ther­apy.

The NCCN guidelines are followed closely by physicians and by many U.S. health insurance com­pa­nies, which frequently use them when making reim­burse­ment decisions about different cancer treat­ments.

The guidelines are comprised of recommendations based on the results of recent clinical trials and ongoing scientific research.  A panel of specialists within the myeloma field is responsible for updating the NCCN guidelines for multiple myeloma.

Previous editions of the NCCN guidelines have included Revlimid (lena­lido­mide) main­te­nance ther­apy as a so-called "Category 2A" recommendation.  Such recommendations are considered by the NCCN to be based on "lower-level evidence."

The newest edition of the NCCN guidelines, in contrast, lists Revlimid main­te­nance ther­apy as a "Category 1" recommendation, meaning the NCCN believes the recommendation is supported by "high-level evidence."

This is important as there has been significant debate over whether the benefits of Revlimid main­te­nance ther­apy outweigh its risks.

Results from three major studies of Revlimid main­te­nance ther­apy were pub­lished in May.  All three trials found that Revlimid main­te­nance ther­apy signifi­cantly delayed the pro­gres­sion of multiple myeloma, and one of the studies found that Revlimid main­te­nance ther­apy improved the over­all survival of patients (see related Beacon news).

At the same time, all three trials revealed that patients who received Revlimid main­te­nance ther­apy were significantly more likely to experience a second cancer than those who did not receive Revlimid.

Data linking Revlimid to an increased risk of second cancers became public in 2010, and in 2011 the European Medicines Agency (EMA) as well as the U.S. Food and Drug Administration (FDA) began investi­ga­tions into Revlimid's safety.

The EMA concluded that the benefits of Revlimid, particularly improved survival, outweighed the risks. How­ever, the agency recommended that the pre­scrib­ing in­­for­ma­tion for Revlimid be updated with a warning and advice to doctors on the risk of new cancers (see related Beacon news).

The FDA investigation also resulted in a warning being added to the Revlimid pre­scrib­ing in­­for­ma­tion stating that patients being treated with the drug have an increased risk of developing a second cancer (see related Beacon news).

The newly released NCCN guidelines contain language about Revlimid main­te­nance ther­apy similar to the warnings now included in the U.S. and European pre­scrib­ing in­­for­ma­tion for the drug.  The language, though, is more tentative about the link between Revlimid and second cancers.

The guidelines note, "There appears to be an increased risk for secondary cancers, especially with [Revlimid] main­te­nance fol­low­ing trans­plant.  The benefits and risk of main­te­nance ther­apy vs. secondary cancers should be discussed with patients."

Revlimid is marketed in the U.S. and elsewhere by Celgene (NASDAQ: CELG).  The com­pany's stock was up 2.5 per­cent on yesterday while the stock market as a whole was unchanged.

In addi­tion to Revlimid, the NCCN guidelines also list thalidomide (Thalomid) and Velcade (bor­tez­o­mib) as preferred main­te­nance ther­a­pies, with thalido­mide main­te­nance supported by "high-level evidence" and Velcade main­te­nance by "lower-level evidence."

Several addi­tional changes were made in the latest version of the NCCN guidelines.

The guidelines now state that for Velcade-based regi­mens, physicians should consider using subcu­tane­ous Velcade, instead of intravenous Velcade, for patients with pre-existing periph­eral neu­rop­athy or who are at high-risk of developing neu­rop­athy.  Peripheral neu­rop­athy is nerve damage that results in pain, tingling, or loss of sensation in the extremities.

The recommendations for the treat­ment of re­lapsed and refractory myeloma, known as salvage ther­apy, were also updated.

Specifically, Velcade-thalidomide-dexamethasone (Decadron) along with Kyprolis (car­filz­o­mib) were both added as preferred regi­mens supported by "lower-level evidence."  These were added to a long list of already-preferred salvage regi­mens, including repeating the patient's initial ther­apy if it provided a remission of more than six months as well as a number of other Velcade-, Revlimid-, and chemotherapy-based regi­mens.

The addi­tion of Kyprolis to the guidelines is accompanied by a note stating that Kyprolis is approved for patients who have received at least two prior ther­a­pies, including Velcade and an immuno­modu­la­tory agent, meaning either Revlimid, thalido­mide, or pomalidomide.  The patients must also have dem­onstrated disease pro­gres­sion on or within 60 days of completing their last ther­apy.

Two regi­mens were also added to the list of "other salvage regi­mens."  Those include Velcade-Zolinza (vorinostat) and Revlimid-Treanda (bendamustine)-dexamethasone, both of which were listed as supported by "lower-level evidence."

For more in­­for­ma­tion, see the NCCN guidelines for multiple myeloma (free registration required) as well as Beacon articles about pre­vi­ous updates to the NCCN myeloma guidelines.