Smoldering multiple myeloma current treatment algorithms

Abstract

Smoldering multiple myeloma (SMM) is an asymptomatic condition that occupies a space between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) along the spectrum of clonal plasma cell proliferative disorders. It is not a biologic intermediate stage between MGUS and MM, but rather represents a heterogeneous clinically defined condition in which some patients (approximately two-thirds) have MGUS (pre-malignancy), and some (approximately one-third) have MM (biologic malignancy). Unfortunately, no single pathologic or molecular feature can reliably distinguish these two groups of patients. For purposes of practice and clinical trials, specific risk factors are used to identify patients with SMM in whom malignant transformation has already likely occurred (high risk SMM). Patients with newly diagnosed high risk SMM should be offered therapy with lenalidomide or lenalidomide plus dexamethasone (Rd) for 2 years, or enrollment in clinical trials. Patients with low risk SMM should be observed without therapy every 3-4 months.

Fig. 1. Approach to the management of smoldering multiple myeloma.

Footnote for Fig. 1: SMM, smoldering multiple myeloma; MM, multiple myeloma; Rd, lenalidomide plus dexamethasone. Myeloma Defining Events: End organ damage felt to be related to myeloma (hypercalcemia, light chain cast nephropathy, anemia, osteolytic bone lesions), serum free light chain ratio ≥100 with involved serum free light chain level ≥100 mg/dL and urine monoclonal protein ≥200 mg per 24 h on urine protein electrophoresis, ≥60% clonal bone marrow plasma cells, >1 focal lesion on magnetic resonance imaging. High risk Smoldering Multiple Myeloma: Any 2 of the following: bone marrow plasma cells >20%, serum monoclonal protein >2 gm/dL, serum free light chain ratio >20. Or high risk score based on the International Myeloma Working Group Scoring System for Smoldering Multiple Myeloma. Evolving change: Increase in monoclonal protein of 0.5 gm/dl or more along with a concomitant decrease in hemoglobin of 0.5 g/dl or more over a 12-month period.