Impact of early reduction in paraprotein on survival in transplant ineligible myeloma: Lesson from a tertiary cancer center in rural India

Introduction: The impact of rapid reduction in paraprotein levels, with induction chemotherapy in myeloma, on treatment outcomes is less clear. There are very few studies in transplant ineligible patients treated with novel agents, correlating an early reduction in paraprotein with survival duration. Methods: In this retrospective analysis of newly diagnosed multiple myeloma, ineligible for stem cell transplant, paraprotein levels at baseline and 3 months were noted with percentage reduction. Survival analysis was performed with Kaplan–Meier curves and Cox proportional hazard model. Results: Among a total of 121 patients, 42 (35%), 29 (24%), and 50 (41%) had paraprotein reduction of 100%, 90%–99%, and <90%, respectively from baseline levels at 3 months. Patients with complete disappearance of paraprotein (100% reduction) when compared against those with <100% reduction at 3 months had a trend toward higher overall survival (OS) (3-year OS of 81% vs. 69%, hazard ratio [HR] = 0.54, P = 0.182). However, the progression-free survival (PFS) was significantly higher when these two groups were compared (median PFS of 51 vs. 17 months, HR = 0.33, P ≤ 0.001). When patients with ≥90% reduction were compared with <90% reduction at 3 months, there was significant improvement in both OS and PFS (3-year OS of 80% vs. 48%, HR = 0.24, P = 0.001, median PFS of 38 vs. 14 months, HR = 0.13, P < 0.001). Conclusions: Achieving a faster and deeper reduction in paraprotein as early as 3 months could lead to significant improvement in PFS

Association between left ventricular function and paraprotein type in patients with multiple myeloma

BACKGROUND/AIMS: Multiple myeloma (MM)–associated cardiac damage, particularly according to the type of monoclonal (M) protein has not been elucidated. We sought to investigate relationship between elevated serum M protein levels and echocardiographic indices of cardiac structure and function in patients with MM. METHODS: We evaluated a total of 184 consecutive MM patients who underwent echocardiography for bone marrow pre-transplant screening. Serum levels of intact immunoglobulin M protein and free light chain kappa/lambda (FLC-κ/-λ) were measured. RESULTS: One hundred thirty-nine patients were non-light chain MM (non-LCMM) and 45 patients belonged to LCMM. In patients with non-LCMM, significant correlations were found between serum M protein and left atrial volume index (LAVi; r = 0.720, p < 0.0001), E/e’ (r = 0.511, p < 0.0001), and systolic pulmonary arterial pressure (r = 0.485, p < 0.0001). In patients with LCMM, log-transformed FLC-λ (log-λ) was correlated with left ventricular ejection fraction (LVEF, r = –0.536, p = 0.010), left ventricular (LV) end-systolic dimension (r = 0.500, p = 0.018), and LV end-systolic volume (r = 0.444, p = 0.038). On multivariate analyses, hematocrit and serum M protein were independent predictors of LAVi in patients with non-LCMM. In patient with LCMM, FLC-λ isotype was only found to be an independent determinant of LVEF. CONCLUSIONS: An increase in serum M protein was associated with LV diastolic dysfunction, whereas an increase in serum FLC-λ concentration showed a negative correlation with the echocardiographic parameters of LV systolic function. These findings also suggest that serum M protein has different effects on LV function according to the type of paraproteins in patients with MM.

Association between left ventricular function and paraprotein type in patients with multiple myeloma

BACKGROUND/AIMS: Multiple myeloma (MM)–associated cardiac damage, particularly according to the type of monoclonal (M) protein has not been elucidated. We sought to investigate relationship between elevated serum M protein levels and echocardiographic indices of cardiac structure and function in patients with MM. METHODS: We evaluated a total of 184 consecutive MM patients who underwent echocardiography for bone marrow pre-transplant screening. Serum levels of intact immunoglobulin M protein and free light chain kappa/lambda (FLC-κ/-λ) were measured. RESULTS: One hundred thirty-nine patients were non-light chain MM (non-LCMM) and 45 patients belonged to LCMM. In patients with non-LCMM, significant correlations were found between serum M protein and left atrial volume index (LAVi; r = 0.720, p < 0.0001), E/e’ (r = 0.511, p < 0.0001), and systolic pulmonary arterial pressure (r = 0.485, p < 0.0001). In patients with LCMM, log-transformed FLC-λ (log-λ) was correlated with left ventricular ejection fraction (LVEF, r = –0.536, p = 0.010), left ventricular (LV) end-systolic dimension (r = 0.500, p = 0.018), and LV end-systolic volume (r = 0.444, p = 0.038). On multivariate analyses, hematocrit and serum M protein were independent predictors of LAVi in patients with non-LCMM. In patient with LCMM, FLC-λ isotype was only found to be an independent determinant of LVEF. CONCLUSIONS: An increase in serum M protein was associated with LV diastolic dysfunction, whereas an increase in serum FLC-λ concentration showed a negative correlation with the echocardiographic parameters of LV systolic function. These findings also suggest that serum M protein has different effects on LV function according to the type of paraproteins in patients with MM.

A Patient with IgA Monoclonal Gammopathy Presenting as Myelomatous Pleural Effusion with Axillary Node Involvement

Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin, and the neoplastic plasma cells typically accumulate in the bone marrow with occasional involvement of other organs. Pleural effusion that is associated with multiple myeloma has been infrequently reported (<6%) and myelomatous pleural effusion is extremely rare (<1%). A 73-year-old woman was admitted to the department of dermatology for skin lesions on both arms and both ankles. A chest radiograph taken on admission showed a nodular lesion in the right upper lung and pleural effusion. Analysis of the pleural fluid revealed many atypical plasma cells, elevated levels of IgA (27.95g/L) and lambda light chain (9.16g/L), and monoclonal IgA-lambda paraprotein on immunofixation. The serum concentrations of IgA were elevated (33.08g/L) while the concentrations of IgG and IgM were decreased. Bone marrow aspirate smears contained increased levels of immature-appearing atypical plasma cells. This is only the third case of myelomatous pleural effusion that has been reported in Korea.

PREPARATION AND PRELIMINARY CLINICAL APPLICATION OF McAb AGAINST HUMAN IgK AND Ig? / 解放军医学杂志

Five hybridoma cell lines have been developed by fusion of SP2/O or NS-1 myeloma cell with splenocytes of BALb/c mice immunized with colostrum and serum IgA and screened by means of ELI-SA sandwich method. Of these, three lines (1Dl, 5C3, 11A7) secreted antibodies against human free A chains and combined A light chains, while the other two lines (4G12. 14A6) against human free K and combined K light chains. The 4G12 reacted better with combined K chains than with free K chains. These cell lines were stable to secrete specific McAb in long term culture for one year, and after storage in liquid nitrogen for ten months as well. With competitive ELISA using solid phase antigen, McAbs 4G12 and 14A6 were proved to react with different antigen epitopes, while McAbs IDl, 5C3 and 11A7 reacted with same antigen epitopes. These McAbs are good in both specificity and sensitivity for detection of paraproteins and Bence-Jones proteins. Mixed McAbs of 4G12-HRP and 1D1-HRP could be used to detect VCA and EA of EB virus satisfactorily. Preliminary application to the detection of antinuclar antibodies was also successful.