Prognostic utility of serum free light chain ratios and heavy-light chain ratios in multiple myeloma in three PETHEMA/GEM phase III clinical trials

Abstract

We investigated the prognostic impact and clinical utility of serum free light chains (sFLC) and serum heavy-light chains (sHLC) in patients with multiple myeloma treated according to the GEM2005MENOS65, GEM2005MAS65, and GEM2010MAS65 PETHEMA/GEM phase III clinical trials. Serum samples collected at diagnosis were retrospectively analyzed for sFLC (n = 623) and sHLC (n = 183). After induction or autologous transplantation, 309 and 89 samples respectively were available for sFLC and sHLC assays. At diagnosis, a highly abnormal (HA) sFLC ratio (sFLCr) (<0.03 or >32) was not associated with higher risk of progression. After therapy, persistence of involved-sFLC levels >100 mg/L implied worse survival (overall survival [OS], P = 0.03; progression-free survival [PFS], P = 0.007). Among patients that achieved a complete response, sFLCr normalization did not necessarily indicate a higher quality response. We conducted sHLC investigations for IgG and IgA MM. Absolute sHLC values were correlated with monoclonal protein levels measured with serum protein electrophoresis. At diagnosis, HA-sHLCrs (<0.29 or >73) showed a higher risk of progression (P = 0.006). Additionally, involved-sHLC levels >5 g/L after treatment were associated with shorter survival (OS, P = 0.001; PFS, P = 0.018). The HA-sHLCr could have prognostic value at diagnosis; absolute values of involved-sFLC >100 mg/L and involved-sHLC >5 g/L could have prognostic value after treatment.

Minimal residual disease in multiple myeloma: Benefits of flow cytometry

“…According to Martínez‐López, out of 94 patients who achieved CR, 69 patients (73%) achieved sCR, but no significant differences in time to progression were identified in the CR and sCR groups (median value for CR and sCR was 53 and 62 months, respectively). Similar data were obtained in the study by Lopez‐Anglada, which enrolled 130 patients.…”

The clinical significance of stringent complete response in multiple myeloma is surpassed by minimal residual disease measurements

“…In a previous work from our group, we showed that the sCR criteria only identified a small group of patients with dismal prognosis, namely, those with high residual burden by low-sensitivity MFC [12]. We also found that sFLC ratio normalization in patients in CR did not identify patients with differing outcomes [12,13].…”

Serum Free Immunoglobulins Light Chains: A Common Feature of Common Variable Immunodeficiency?

“…These ranges were suggested using reference serum samples from 282 healthy donors between the ages of 21 and 90 years (15), based on the polyclonal Freelite assay. sFLC quantification may indicate the presence of B cell clonality and is widely used in clinical practice for the diagnosis of B-cell lymphoproliferative disorders (B-CLPD), in particular the progression of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM), as well as a marker of neuroinflammation, for instance, in multiple sclerosis (16)(17)(18)(19)(20)(21)(22)(23). Moreover, dysbalance in sFLC is used as a prognostic marker of various B-CLPD, such as chronic lymphocytic leukemia (CLL), B cell non-Hodgkin lymphomas (NHL), as well as for real-time monitoring of response to treatment and disease progression (5,17,(24)(25)(26)(27).…”

“…Individuals with CVID are at 5 to 10-fold higher risk of developing hematological malignancies (36,37,40), while unexpectedly lower incidence on most common cancers than general population has been described (41,42). Cancer is a leading cause of mortality in PID, and thus early diagnosis and treatment of malignancy is a priority (22,43). When comparing the κ/λ ratio in both cohorts, SID showed significantly higher κ/λ ratio (p < 0.005), as expected (7,29,43).…”