Researchers Define When Light Chain Amyloidosis is Multiple Myeloma

Histopathological image of multiple myeloma; source: KGH, Wikimedia Commons

Researchers have helped to better define the spectrum of light chain (AL) amyloidosis by identifying that AL amyloidosis patients with myeloma who have more than 10% bone marrow plasma cells (BMPCs) or those with hypercalcemia, renal failure, anemia, and lytic bone lesions (CRAB) have a similar prognosis to patients with overt myeloma.

“Up to now, multiple definitions for ‘AL amyloidosis with myeloma’ have been used,” Angela Dispenzieri, MD, of the Mayo Clinic, told Cancer Network. “Some investigators use CRAB-calcium, renal anemia, bone lesions-some use 20% bone marrow plasma cells, and some use 30% bone marrow plasma cells. We want to understand what the ‘best’ or ‘most correct’ definition was to work toward standardization.”

Dispenzieri and colleagues identified 1,255 patients with AL amyloidosis seen within 90 days of diagnosis between 2000 and 2010. First the researchers identified a group of patients with coexisting multiple myeloma based on presence of CRAB criteria (AL-CRAB). In addition, an analysis was conducted to identify the 10% bone plasma cells cutoff, and based on that, two additional groups were identified: AL only (10% BMPCs or less) and AL plasma cell multiple myeloma (AL-PCMM; greater than 10% BMPCs).

The 100 patients (8%) identified has having AL-CRAB had a median overall survival of 10.6 months compared with 16.2 months among the 476 (38%) patients with AL-PCMM, and 46 months among the 679 (54%) patients with AL only (P < .001).

“We found that using the threshold of 10% bone marrow plasma cells was the best cut-point to predict for overall survival,” Dispenzieri said. “Having more than 10% bone marrow plasmacytosis was as risky for a patient as having overt myeloma as defined by CRAB.”

Univariate analyses showed that worse overall survival was predicated by age (P < .001), 2004 and 2012 Mayo AL amyloidosis stage (P < .001), difference between the involved and uninvolved free light chain (dFLC) of more than 18 mg/dL (P < .001), history of autologous stem cell transplantation (P < .001), AL-CRAB vs AL only (P < .001), and AL-PCMM vs AL only (P < .001). 

Because outcomes were similar, the researchers pooled patients with AL-CRAB and AL-PCMM for multivariate analyses, which showed that AL-CRAB and AL-PCMM, as well as age, Mayo AL amyloidosis stage, dFLC and history of autologous stem cell transplantation all retained their negative prognostic value.

“I think this will help physicians who deal with AL amyloidosis to speak the same language, which is always important, and it may affect how we stratify patients in clinical trials,” Dispenzieri said. “It reminds us about how fascinating bone marrow plasma cells are. For unclear reasons, the biology of bone plasma cells appears to change dramatically once the 10% threshold is reached.”