The National Comprehensive Cancer Network (NCCN) recently released an updated version of its guidelines for the diag­nosis and treat­ment of multiple myeloma.

The most notable change to the guidelines is the addi­tion of Kyprolis (carfilz­omib), in com­bi­na­tion with Revlimid (lena­lido­mide) and dexa­metha­sone (Decadron), as an alter­na­tive treat­ment option for newly diagnosed myeloma patients eligible for a stem cell trans­plant.

The guidelines also now list Pomalyst (poma­lido­mide), in com­bi­na­tion with dexa­meth­a­sone, as a preferred salvage treat­ment for myeloma.

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 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.

The pre­vi­ous edition of the NCCN myeloma guidelines added Kyprolis as a preferred salvage ther­apy, which aligns with its approved use.

Kyprolis is cur­rently approved by the U.S. Food and Drug Administration (FDA) for use in myeloma patients who have received at least two prior ther­a­pies, including Velcade (bor­tez­o­mib) and an immuno­modu­la­tory agent, meaning either thalidomide (Thalomid), Revlimid, or Pomalyst.

The FDA-approved use also stipulates that patients must also have dem­onstrated disease pro­gres­sion on or within 60 days of completing their last ther­apy.

Kyprolis-Revlimid-Dexamethasone In The New Guidelines

In the recently updated edition of the NCCN guidelines, Kyprolis in com­bi­na­tion with Revlimid and dexa­meth­a­sone has been added as an "other" (alternative) initial ther­apy for myeloma patients who are eligible for stem cell trans­plan­ta­tion.

The addi­tion is accompanied by a footnote stating that the optimal dosing of the Kyprolis-Revlimid-dexamethasone regi­men has not yet been defined.

The NCCN myeloma guidelines list separate treat­ment options for trans­plant-eligible and trans­plant-ineligible patients because this categorization of newly diagnosed patients is common among myeloma specialists. It is used even though many trans­plant-eligible patients do not necessarily receive a trans­plant as part of their initial myeloma ther­apy.

Transplant eligibility is typically based on the age (a cutoff of about 70 is common in the U.S.) and general health of a patient.

As in the past, the current edition of the NCCN guidelines also lists several "preferred" treat­ments for newly diagnosed, trans­plant-eligible myeloma patients.  Those regi­mens include: Velcade-dexamethasone, Revlimid-dexamethasone, Velcade-Revlimid-dexamethasone, and Velcade-cyclophosphamide (Cytoxan)-dexamethasone.

The preferred options just listed are described in the guidelines as "Category 1" recommendations.  This means that the NCCN considers the use of the treat­ments to be supported by "high-level evidence ... [with] uniform consensus that the intervention is appropriate."

The listing of the Kyprolis-Revlimid-dexamethasone com­bi­na­tion as an alter­na­tive treat­ment option in the NCCN guidelines is described as a "Category 2A" recommendation.  This means it is based on "lower-level evidence," but still with "uniform NCCN consensus that the intervention is appropriate."

For physicians and patients considering treat­ment with Kyprolis or Velcade, the NCCN also recommends treat­ment to prevent shingles.

Physicians also are advised in the guidelines to consider using sub­cu­tane­ous Velcade for patients with pre-existing or at high risk of developing periph­eral neu­rop­athy (pain, tingling, or loss of sensation in the extremities).

Pomalyst In The New Guidelines

The other major addi­tion in the latest release of the NCCN guidelines is Pomalyst in com­bi­na­tion with dexa­meth­a­sone as a preferred salvage ther­apy.  This com­bi­na­tion, like most of the preferred salvage ther­a­pies, is listed as a Category 2A recommendation.

The guidelines add that single-agent Pomalyst, without dexa­meth­a­sone, can be considered for patients unable to tolerate steroids.

The FDA last month approved Pomalyst, alone or in com­bi­na­tion with dexa­meth­a­sone, as a new treat­ment for myeloma patients who have received at least two prior ther­a­pies, including Velcade and Revlimid, and who have dem­onstrated disease pro­gres­sion on or within 60 days of completing their last ther­apy (see related Beacon news).

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.