Oligosecretory and Non-Secretory Multiple Myeloma: Incidence, Clinical Characteristics and Outcomes

Patients with multiple myeloma (MM) that present at diagnosis with serum monoclonal protein (MIg) of <1 g/dl and a urine MIg level <200 mg/day (defined as oligosecretory MM) or, less commonly, with negative tests in serum and urine for the presence of a monoclonal protein (non-secretory) are commonly excluded from participation in clinical trials due to “undesirable disease”. The serum FLC assay can be used to monitor many of these patients, if FLC ratio is abnormal and the involved FLC level is ≥100 mg/L. There is, however, a concern whether patients with oligosecretory or non-secretory disease may have different biology and outcomes than patients with “secretory” MM. Among 652 consecutive patients with complete baseline data on serum and urine PEP and immunofixation electrophoresis, who were diagnosed and treated in the Department of Clinical Therapeutics (Athens, Greece) from 2006 to 2015, we identified 52 (8%) patients with serum MIg<1 gr/dl and urine MIg<0.2 gr/day (oligosecretory), including 14 (2%) with negative serum and urine immunofixation (non-secretory). Compared to patients with secretory MM, patients with oligosecretory MM were younger (p=0.09), had less often anemia (p<0.001) or severe renal dysfunction (p=0.05), less extensive bone marrow plasma cell infiltration (p=0.013), high risk cytogenetics [any of del17p, t(4;14) or t(14;16)] (in 10% vs 23%, p=0.1) and were more often ISS-1 (p<0.001); the respective revised-ISS disposition in stages -1,-2 and -3 was 30%, 55% & 15% vs 17%, 62% & 22% respectively (p=0.12). Incidence of lytic bone disease was similar (p=0.22), as well as the extent of bone disease (p=0.13), but hypercalcemia (calcium≥11.5 mg/dl) was less common (6% vs 12%, p=0.17). Median involved FLC (iFLC) for patients with oligosecretory disease was 378 mg/l (range 3-2350) and 66% had iFLC ≥100 mg/L. Treatment was similar to that of other MM patients. Median follow up is 50 months; the 5-year OS for patients with oligosecretory disease is 58% vs 48% for the rest of the patients (p=0.3). Patients with non-secretory disease (both serum and urine immunofixation negative) compared to other MM patients, were younger (p=0.02), less anemic (p=0.013), only one patient (7%) had eGFR<30 ml/min (vs 23%, p=0.17), were more often ISS-1 (50% vs 24%) than ISS-2 (21% vs 33%) or ISS-3 (29% vs 43%) (p=0.08), had similar bone marrow plasma cell infiltration, but, lytic bone disease (92% vs 75%, p=0.15) and hypercalcemia were more common (21% vs 12%, p=0.25). No high risk cytogenetics were detected in patients (n=5) with available iFISH. Only 2/12 patients had normal FLC ratio and thus could be rated as “true” non secretory myeloma. The other patients had abnormal FLC ratio and 6/12 had iFLC≥100 mg/L. Patients with “non-secretory” myeloma had a trend for longer survival (5 year OS 68% vs 48% for the others, p=0.12).