Secondary Monoclonal Gammopathy Of Undetermined Significance Is Frequently Associated With High Response Rate and Superior Survival In Patients With Plasma Cell Dyscrasias

Secondary monoclonal gammopathy of undetermined significance (MGUS) is a special phenomenon during the treatment of multiple myeloma (MM). The incidence, biological characteristics and prognostic value of secondary MGUS in patients with MM remain undefined.

Serum immunofixation electrophoresis (IFE) was retrospectively analyzed in 438 cases of patients with plasma cell dyscrasias, including 409 cases of newly diagnosed MM and 29 cases of primary plasma cell leukemia (pPCL). Patients who developed a secondary MGUS were identified through a retrospective analysis of serum immunofixation electrophoresis (IFE). IFE test was performed with Sebia Hydragel kits on the Sebia Hydrasys electrophoresis system (Sebia, Norcross, GA) using agarose gels. The identification of secondary MGUS required the detection of at least one new monoclonal (M) protein with heavy and/or light chain immunoglobulin different from the initially diagnosed MM

Secondary MGUS was more common in patients with myeloma who had undergone SCT than in those who had not (17 [29.8%] out of 57 versus 5 [1.4%] out of 352, P < 0.001). The clinical parameters and cytogenetic characteristics in patients with or without secondary MGUS were comparable. The overall CR rates in patients with or without secondary MGUS were 81.8% and 21.8% respectively (p<0.01).

The median PFS and OS of the entire cohort with MM was 25.0 months (95% CI: 19.9-30.0) and 36.0 months (95% CI: 29.4-42.6), respectively. Despite the small number of patients with secondary MGUS, these patients had a clearly better disease outcome as compared with those without secondary MGUS. The median PFS was 52.0 months (95% CI: 41.1-62.9) in patients with secondary MGUS versus 22.5 months (95% CI: 19.6-25.4) for the rest of the cohort (P = 0.002). Patients with secondary MGUS also had much longer OS, and the median OS was not reached versus 35.0 months (95% CI: 29.4-40.6) for the patients without secondary MGUS (P < 0.001).

Univariate analysis performed on the whole group of 409 patients identified several prognostic factors that had significant negative effect on OS. These factors included advanced International Staging System stage (P<0.001), 17p deletion (P<0.001), 13q deletion (P=0.009), t(4;14) (P=0.042), 1q gains(P=0.006), absence of secondary MGUS (P<0.001). A multivariate Cox regression model including ISS stage, chromosome aberration determined by FISH and secondary MGUS was applied. The presence of secondary MGUS retained independent prognostic values for OS (HR 0.128 [95% CI 0.018-0.922], p=0.041). A similar analysis for prediction of PFS did not identify presence of sMGUS as independent prognostic factor.

Survival was then analyzed in patients undergoing stem cell transplantation. Patients with secondary MGUS seemed to have a longer median PFS, but the difference was not statistically significant (52 months versus 41.0 months; p=0.126). Median OS was not reached in both group and no statistical difference was found (p=0.220)

We observe that secondary MGUS is frequently observed in MM patients after transplantation, and associated with a more favorable prognosis. The clinical parameters and cytogenetic characteristics in patients with or without secondary MGUS are comparable. The favorable survival could be explained by the higher depth of response especially after myeloablative therapy.

No relevant conflicts of interest to declare.