Updates to the National Comprehensive Cancer Network's guidelines for treating multiple myeloma include new criteria for initiating treatment and an expanded menu of therapies based on recent FDA approvals. The changes extend the population of patients eligible for treatment and provide oncologists with better prognostic tools.

Patients diagnosed with multiple myeloma should begin treatment before symptoms arise, according to updated clinical guidelines issued by the National Comprehensive Cancer Network. The new guidelines, available at www.nccn.org, also include an expanded menu of preferred treatment options and a more accurate method of predicting disease progression.

“In the past, we've waited for symptoms to appear before starting therapy,” says Kenneth Anderson, MD, professor of medicine at Harvard Medical School and Dana-Farber Cancer Institute in Boston, MA, and chair of the panel that developed the guidelines. “By treating patients earlier, hopefully we can prevent those complications from developing”

Traditionally, treatment was triggered by the emergence of a constellation of symptoms known as CRAB (calcium elevation, renal insufficiency, anemia, or bone abnormalities), says Anderson. Under the revised guidelines, patients can be treated based on any one of the following three diagnostic criteria: greater than 60% plasma cells in the bone marrow; free immunoglobulin light-chain ratio greater than 100 (indicative of abnormal immunoglobulin production by neoplastic plasma cells); or more than one bone lesion larger than 5 mm.

“Recent data indicate that each of these three criteria independently correlate quite closely with progression of disease within 2 years,” says Damian Green, MD, assistant professor of medicine at the University of Washington School of Medicine and Fred Hutchinson Cancer Research Center in Seattle. “As a result, any one of them can be a rationale for starting therapy. We no longer have to wait until someone has end-organ damage”

The panel also recommended changes in how patients are stratified at diagnosis using the International Staging System (ISS), which relies on levels of albumin and beta-2 microglobulin in the blood. The revised ISS incorporates cytogenetics, which will allow oncologists to better predict patients' long-term outcomes based on their genetic mutations (J Clin Oncol 2015;33:2863–9).

“The old system was simple and quite accurate, but it had limitations because it was developed before the advent of more effective therapies and routine cytogenetic profiling,” says Green. “We now have data on patients who have received these novel treatments, which allows us to more accurately stratify current patients and predict outcomes”

The most significant change for newly diagnosed patients is the combined use of lenalidomide (Revlimid; Celgene), bortezomib (Velcade; Millennium/Takeda), and dexamethasone as a preferred regimen, says Anderson. In a phase III trial, the triplet combination led to significantly longer progression-free survival compared with lenalidomide plus dexamethasone.

For the first time, the guidelines for initial therapy also include a combination of three oral therapies, notes Anderson. The combination includes the proteasome inhibitor ixazomib (Ninlaro; Takeda) plus lenalidomide and dexamethasone.

The panel also added new agents and classes of drugs to treat relapsed disease, he says. These include panobinostat (Farydak; Novartis), a histone deacetylase inhibitor, in combination with bortezomib/dexamethasone, as well as two monoclonal antibodies—elotuzumab (Empliciti; Bristol-Myers Squibb), which targets SLAMF7, and daratumumab (Darzalex; Janssen), which targets CD38. Elotuzumab is approved in combination with lenalidomide and dexamethasone; daratumumab is approved as a single agent.

“This is the first time that monoclonal antibodies have been used to treat this disease,” says Anderson. “These updated guidelines reflect the multiple new options we now have for the management of initial and relapsed myeloma.” –Janet Colwell

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