Clinical Features and Outcomes of Light-Chain Dominant Multiple Myeloma: A Population-Based Study

Background: There is a certain subgroup of multiple myeloma(MM) patients shows serum and urine monoclonal protein level that is negative or below thresholds considered to be measurable (Oligosecretory and non-secretory MM). In this subgroup the serum free-light-chain (FLC) assay can be used to monitor treatment response if the patient shows abnormal FLC ratio and more than 100 mg/L of involved FLC level. Yet studies about treatment outcome and clinical features in this particular patient group are still lacking. We aimed to conduct a population based study about light-chain dominant MM (LcDMM) in Korea.

Methods: We performed a single-center retrospective study based on the MM patients referred to the Hematology Unit of Seoul National University Hospital from 2005 to 2015. LcDMM was defined as oligosecretory or non-secretory MM with more than 1,000 mg/dL of involved light chain. We analyzed for demographic and clinical characteristics as well as overall survival (OS) and progression free survival(PFS). Also we wanted to see whether there was a difference between characteristics of kappa and lambda LcDMM.

Results: A total of 157 LcDMM cases were identified including 37 (23.5%) patients with non-secretory MM. Comparing with previously published general MM population data. LcDMM patients were younger (Median age at diagnosis = 60 years, with 66.2% of diagnosed patients being <60 years) and showed higher proportion of female (Male 51.6%). The International Staging System (ISS) distribution in stage I, II, and III was 40.4%, 19.9% and 39.7%. Among patients with available cytogenetic data, half of the patients had normal karyotype (49.0%) and the prevalence of several cytogenetic abnormalities with poor prognosis including t(4;14), del(17/17p) and t(14;16) was 1.9%, 7.0%, and 1.3% respectively.

More than half of the patients were lambda-FLC involved MM (54.8%). Half of the lambda. LcDMM was ISS stage II at diagnosis (46.2%), and in contrast, half of the kappa LcDMM was Stage I (48.5%). The incidence of extramedullary organ involvement was not significantly different between kappa and lambda LcDMM. The median overall survival (OS) from diagnosis of whole LcDMM patients was 59.4 months and of each (ISS) stage was 62 months, 57 months, and 44 months in Stage I, II and III. The median OS of kappa and lambda LcDMM was 69.2 months (95% confidence interval (CI) = 38.6 to 99.7) and 40.3 months (95% CI = 16.4 to 64.1), but there was no statistically significant difference (Plogrank = 0.317)

Previous exposure to thalidomide, lenalidomide, and bortezomib was 56.7% (n=89), 21.7% (n=34), and 72.3% (n=112), respectively, and 43.9% (n=69) of patients underwent hematopoietic stem cell transplantation (HSCT). Median PFS of kappa and lambda LcDMM after thalidomide treatment was 11.8 months vs 5.5 months. After lenalidomide treatment, median PFS was not reached yet. In bortezomib, lambda LcDMM showed higher median PFS than kappa LcDMM (9.0 vs 30.0). But, again, there was no statistically significant difference (Plogrank =0.214, 0.506, 0.786)

Conclusion : Patients with LcDMM shows several clinical characteristics that clearly is distinguished from secretory MM. In general, the type of light chain is known to have no effect on the prognosis of MM. Yet there was a certain tendency of worse prognosis to lambda FLC involved patients in this study, and bortezomib might be considered for better response in this population. There is a limitation in statistical power of this study due to small population. But this is the largest population based study of all previously published single-center oligosecretory or non-secretory MM study and is also the first study on Asian population.