Altered Plasma Cell Characteristics in Smoldering Myeloma and MGUS Patients with Preceding Immune-Related Conditions

Emerging evidence from epidemiological studies suggests that immune-related conditions play a role in the causation of multiple myeloma (MM) precursor disease (smoldering myeloma, SMM; and monoclonal gammopathy of undetermined significance, MGUS) and is of clinical importance for the risk of developing MM. Recent guidelines emphasize tailored follow-up and the need for clinical trials for high-risk SMM. Aim of our study was to assess whether there is an altered biology in SMM/MGUS patients with preceding immune-related conditions.

From our ongoing prospective SMM/MGUS natural history study, we evaluated 85 SMM and 74 MGUS patients. Information on autoimmunity was identified at baseline. All patients underwent extensive clinical and molecular characterization. At baseline, all patients underwent bone marrow biopsy evaluation with immunohistochemistry and were assessed for expression patterns of adverse (CD56, CCND1, CD117) plasma cell biology, and applied risk-models based on serum immune markers and bone marrow characteristics. For the purpose of comparison, SMM/MGUS patients were compared to 29 patients newly diagnosed MM.

Among enrolled SMM and MGUS patients, 10 (12%) and 12 (16%) had a preceding autoimmune disorder; 75 (88%) of SMM and 62 (84%) of MGUS patients did not have a preceding autoimmune disorder. In accordance with our previous findings, we found SMM/MGUS patients with (vs. without) preceding autoimmune disorders to have substantially lower rates of CD56 (p=0.004), CCND1 (p=0.02) and CD117 (p=0.11) expressing plasma cells. For SMM and MGUS patients with preceding autoimmunity, the proportion of CD56, CCND1 and CD117 positive plasma cells was virtually the same. Compared to newly diagnosed MM patients, MGUS or SMM patients with a preceding autoimmune disorder had significantly lower rates of CD56 (p=0.04) and CCND1 (p=0.06) expressing plasma cells; SMM patients without preceding autoimmunity were non-differential from newly diagnosed MM. For SMM patients without preceding autoimmunity newly diagnosed MM patients, the proportion of CD56, CCND1 and CD117 positive plasma cells was very similar. Using Mayo Clinic risk-model, none of the SMM patients with a preceding autoimmune disorder had high-risk features; in contrast, 3/75 (4%) of those without a preceding autoimmune disorder were high-risk SMM. Using Mayo-Clinic risk model, none of the MGUS patients were high-risk independent of autoimmune status.

Our prospective clinical study found SMM patients with preceding immune-related conditions to have less adverse biology, whereas SMM patients without preceding immune-related conditions to have characteristics similar to patients with MM, supportive of epidemiological studies suggesting the risk of developing MM is substantially lower in patients with preceding autoimmunity.

No relevant conflicts of interest to declare.