Updated NCCN Multiple Myeloma Guideline Expands Patient Eligibility and Therapeutic Options

Wayne Kuznar

July 2016, Vol 6, No 7 - Hematologic Malignancies, Multiple Myeloma, NCCN Guidelines Updates


The population of patients with multiple myeloma who are eligible for therapy has been expanded to include asymptomatic patients with certain features, according to the most recent National Comprehensive Cancer Network (NCCN) guideline (version 3.2016).

In addition, among the 7 new drug approvals in 2015 with indications for multiple myeloma, new options for the treatment of patients with relapsed and/or refractory multiple myeloma comprise the first HDAC (histone deacetylase) inhibitor pan­obinostat (Farydak), oral proteasome inhibitor ixazomib (Ninlaro), and the first 2 monoclonal antibodies—daratumumab (Darzalex) and elotuzumab (Empliciti).

Kenneth C. Anderson, MD, Program Director, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, presented the key updates at the 2016 NCCN annual conference.

Eligibility Criteria

Dr Anderson opened his presentation with a review of important changes to the diagnostic criteria for the treatment of patients with multiple myeloma, which expands the active multiple myeloma category and the number of patients eligible for treatment. Historically, eligibility for multiple myeloma treatment demanded abnormalities in the CRAB (calcium, renal function, anemia, and bone disease) features. “However, that is no longer true,” said Dr Anderson.

The new definition of active multiple myeloma in asymptomatic patients, which qualifies such patients for treatment, includes:

  • Bone marrow plasmacytosis ≥60%
  • Abnormal free light chain ratio ≥100 (involved kappa) or <0.01 (involved lambda)
  • Focal bone marrow lesions detected by functional imaging.
For the first time, the NCCN guideline recommends using the revised International Staging System that incorporates cytogenetics for risk stratification.

An All-Oral Triplet Frontline Treatment

The recommended treatment options for the frontline treatment of transplant-eligible candidates now include bortezomib (Velcade) plus lenalidomide (Revlimid) and dexamethasone (category 1), and ixazomib in combination with lenalidomide plus dexamethasone (category 2A).

“For the first time, we have a triplet consisting entirely of oral medications included as initial treatment” for multiple myeloma, Dr Anderson said.

An all-oral regimen of ixazomib plus lenalidomide and dexamethasone yielded a 100% response rate in patients with newly diagnosed multiple myeloma, and ixazomib monotherapy enhanced these responses during maintenance treatment.

Dr Anderson noted that triplet therapy with bortezomib plus lenalidomide and dexamethasone improved complete response rates (including molecular complete response), progression-free survival (PFS), and overall survival compared with lenalidomide plus dexamethasone.

The recommendation for upfront triplet therapy applies to transplant-eligible candidates and very fit transplant-ineligible patients, Dr Anderson added.

Carfilzomib (Kyprolis) in combination with dexamethasone plus lenalidomide is included in the updated guideline as a category 2A (other) recommendation for the frontline treatment of transplant-eligible patients.

A new standard of care for transplant-ineligible patients with newly diagnosed disease is continuous lenalidomide plus dexamethasone, which was found to significantly extend PFS compared with melphalan plus prednisone and thalidomide.

Treatment of Relapsed and/or Refractory Disease

In the relapsed setting, carfilzomib plus lenalidomide and dexamethasone extended PFS by 6 months compared with lenalidomide plus dexamethasone, regardless of whether patients had high-risk or standard cytogenetics; therefore, it is included in the updated guideline as a cate­gory 1 recommendation.

Ixazomib, panobinostat, elotuzu­mab, and daratumumab are among the new therapeutic options in­cluded in the updated NCCN guideline for the treatment of patients with previously treated multiple myeloma.

Ixazomib is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least 1 previous therapy, and is classified as a category 1 recommendation.

Panobinostat added to bortezomib and dexamethasone improved the median PFS by 4 months, and increased the rates of complete response and near complete response compared with bortezomib plus dexamethasone in patients with previously treated multiple myeloma; this combination is classified as a category 1 recommendation.

Elotuzumab was approved in combination with lenalidomide and dexamethasone for previously treated multiple myeloma.

Daratumumab “was approved as a single agent, because it achieved about a 30% response rate even in patients whose myeloma was resistant to bortezomib and lenalidomide,” Dr Anderson said.