NCCN Multiple Myeloma Guidelines Updates

At the National Comprehensive Cancer Network (NCCN) 15th Annual Conference, George Somlo, MD, City of Hope Comprehensive Cancer Center, presented the updates to the NCCN Multiple Myeloma Guidelines. Solmo started the session by providing an overview of multiple myeloma, noting that approximately 20,580 new cases would be diagnosed this year. This disease, which occurs more frequently in African Americans than in whites and primarily affects older individuals (median age, 66 years), generally presents with bone pain, with loss of height often being the first sign. Patients may also experience constitutional weakness, anemia, and renal compromise when the disease becomes more aggressive.

According to Somlo, it is important to perform cytogenetic analysis to determine prognosis, noting that certain chromosomal abnormalies documented by FISH carry a worse prognosis, such as t(4; 14) or t(14; 16). Unilateral bone marrow aspirate plus biopsy, including bone marrow immunohistochemistry and bone marrow flow cytometry, were added to the initial diagnostic workup, whereas use of C-reactive protein was removed as a potentially useful diagnostics for some patients.

The Guidelines indicate that patients who have smoldering myeloma may be observed at 3- to 6-month intervals; this is a class 1 indication. For those requiring treatment, VAD (vincristine, adriamycin, and dexamethasone), melphalan, prednisone, or dexamethasone alone are not acceptable frontline treatment options in 2010, noted Solmo. “First of all, one has to decide whether any particular patient with active multiple myeloma is a candidate for stem cell transplantation,” he said. "The goal still is to get a patient into as close to a complete response as possible, or at least a very good partial response, and then proceed to a stem cell transplant" and consider whether an adjuvant regimen may be necessary. The Guidelines classify a complete response as negative immunofixation on the serum and urine, disappearance of soft tissue plasmacytomas, and ≤5% plasma cells in bone marrow. “Almost as good is very good partial response (VGFR),” noted Somlo. VGFR is considered a 90% or more decrease in serum M-protein and a urine M-protein level <100 mg per 24 hours. “Anything less than that is considered a partial response and it's not good enough,” said Somlo.

For patients with ISS Stage 2 or DS Stage III disease, the guidelines recommend induction with thalidomide/dexamethasone, bortezomib/dexamethasone, lenalidomide/dexamethasone, or a combination of three agents. For patients with active sympatomc myeloma who are in response after induction therapy, there are also options, noted Somlo. These include autologous stem cell transplantation, continuation of the induction regimen until there is a plateau, or possible stem cell transplantation. Somlo noted that melphalan should be avoided because of the risk for significant toxicity, particularly in older patients.

Single agent lenalidomide was also added as an option for maintenance therapy. This recommendation is a category 2A because although lenalidomide has been evaluated in three independent clinical trials, and results of each showed improvements in time to progression, the results of these studies have not yet undergone full peer-review and their safety and efficacy data are still preliminary.

To view the full NCCN Multiple Myeloma Guidelines, visit the NCCN Website.