Multiple Myeloma Defined by Light Chain Amyloidosis With Plasma Cell or CRAB Criteria
In a study reported in Journal of Clinical Oncology, Taxiarchis V. Kourelis, MD, and colleagues from the Mayo Clinic attempted to define a threshold of bone marrow plasma cell number that could serve to define light chain amyloidosis as light chain amyloidosis with multiple myeloma. They found that light chain amyloidosis plasma cell multiple myeloma could be defined as presence of > 10% bone marrow plasma cells, with light chain amyloidosis plasma cell multiple myeloma and light chain amyloidosis satisfying CRAB criteria (hypercalcemia, renal failure, anemia, and lytic bone lesions attributable to clonal expansion of plasma cells) being associated with a similarly poor prognosis. The findings suggest that both conditions should be considered light chain amyloidosis with multiple myeloma.
Study Details
Between January 2000 and December 2010, 1,255 patients with systemic light chain amyloidosis were evaluated at the Mayo Clinic within 90 days of diagnosis. Patients with light chain amyloidosis satisfying CRAB criteria were identified, and receiver operating characteristic analysis showed that the optimal bone marrow plasma cell cut point for predicting 1-year mortality in patients with light chain amyloidosis without CRAB was ≤ 10% bone marrow plasma cells (light chain amyloidosis only) and > 10% bone marrow plasma cells (light chain amyloidosis plasma cell multiple myeloma).
Of the 1,255 patients, 100 (8%) had light chain amyloidosis with CRAB criteria, 476 (38%) had light chain amyloidosis plasma cell multiple myeloma, and 679 (54%) had light chain amyloidosis only.
Overall Survival Results
Median overall survival was 10.6 months in the light chain amyloidosis with CRAB criteria group, 16.2 months in the light chain amyloidosis plasma cell multiple myeloma group, and 46 months in the light chain amyloidosis–only group (P < .001). Median overall survival in patients with light chain amyloidosis with CRAB criteria was significantly shorter compared with that in all other patients with light chain amyloidosis (10.6 vs29 months, P < .001) as was overall survival in patients with light chain amyloidosis plasma cell multiple myeloma compared with light chain amyloidosis–only patients (16 vs 46 months, P < .001).
Among patients who had undergone autologous stem cell transplant, 5-year overall survival rates were 54% in light chain amyloidosis with CRAB criteria patients, 46% in light chain amyloidosis plasma cell multiple myeloma patients, and 73% in light chain amyloidosis–only patients (P < .001). Among those who had not undergone autologous stem cell transplant, 5-year overall survival rates were 11%, 19%, and 31%, respectively (P < .001).
Reduced Survival With Pooled Groups
On univariate analysis, overall survival was significantly associated with age, dFLC (difference between involved and uninvolved free light chains) > 18 mg/dL, 2004 Mayo light chain amyloidosis stage, 2012 Mayo light chain amyloidosis stage, autologous stem cell transplant, light chain amyloidosis with CRAB criteria vs light chain amyloidosis only (P < .001), and light chain amyloidosis plasma cell multiple myeloma vs light chain amyloidosis only (P< .001), but not with light chain amyloidosis with CRAB criteria vs light chain amyloidosis plasma cell multiple myeloma (P = .08).
On multivariate analysis including 2004 Mayo light chain amyloidosis stage and excluding 2012 Mayo stage, the pooled light chain amyloidosis plasma cell multiple myeloma and light chain amyloidosis with CRAB criteria groups had significantly increased risk of death compared with light chain amyloidosis–only patients (relative risk [RR] = 1.28, P = .02). Similar results were found on multivariate analysis including 2012 Mayo stage and excluding 2004 Mayo stage (RR = 1.37, P = .004).
The investigators concluded that patients with light chain amyloidosis with multiple myeloma defined either by CRAB or by more than 10% bone marrow plasma cells have a similarly poor prognosis and could be considered as one group. However, they noted that because the presence of light chain organ involvement increases these patients’ risk for drug toxicity and treatment-related mortality, they should not be treated exactly like patients with multiple myeloma.
“Rather, we hope that patients with [light chain amyloidosis with CRAB criteria] will be considered for clinical trials in general, and that they, along with the patients with [light chain amyloidosis plasma cell multiple myeloma], may be the focus of specific trials that address whether the benefit of more myeloma-like therapy outweighs the risks,” they wrote.
The study was supported in part by the Jabbs Foundation, Predolin Foundation, and Robert A. Kyle Hematologic Malignancies Fund, and Howard Weitzman’s 2011 Gala in Support of Amyloid Research and Awareness.
Angela Dispenzieri, MD, of the Mayo Clinic, is the corresponding author for the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
