ROLE OF HEAVY/LIGHT CHAIN ASSAY, ALONE AND IN COMBINATION WITH FREE LIGHT CHAIN ASSAY AND MINIMAL RESIDUAL DISEASE, IN MYELOMA PATIENTS WHO ACHIEVE COMPLETE RESPONSE AFTER FIRST LINE TREATMENTS
(Abstract release date: 05/21/15)
EHA Library. Musto P. 06/12/15; 102995; PB1887
Disclosure(s): IRCCS, Referral Cancer Center of BasilicataScientific Direction
Dr. Pellegrino Musto
Contributions
Contributions
Abstract
Abstract: PB1887
Type: Publication Only
Background
The International Myeloma Working Group (IMWG) guidelines recommend the use of protein electrophoresis, serum/urine immunofixation and free light chain (FLC) assay for assessing response to treatment in multiple myeloma (MM). In this setting, flow cytometry (FC) is emerging as a useful, though difficult to standardize, additional tool to detect minimal residual disease (MRD). Furthermore, the novel heavy/light chain (HLC) assay has recently become available to improve quantification of IgG and IgA MM isotypes.
Aims
To evaluate the effect of HLC ratio, FLC ratio and MRD on clinical outcome of MM patients achieving immunofixation negative complete response (CR) after first line therapy, according to IMWG criteria.
Methods
We followed a prospective cohort of 25 patients with MM (14 males, 11 females; median age 63.2, range 43-82; 14 IgG and 11 IgA) who had achieved CR after initial treatments including novel agents, with (n. 11) or without (n. 14) autologous stem cell transplantation (AuSCT). CR was identified after 6 induction cycles in patients not eligible for AuSCT and after AuSCT in those undergoing such a procedure. Sera samples were tested for HLC and FLC ratios by commercially available immunonephelometry kits, while bone marrow samples were analyzed by multiparametric FC for assessing MRD, using a home-made method based on a combination of CD138, CD38, CD56, CD19, CD45, CD20, and CD117 monoclonal antibodies. MRD was defined negative if < 10 neoplastic plasma cells were detected in a 100.000-event file. The Kaplan-Meier method was used to plot and calculate progression free survival (PFS ) and overall survival (OS). Variables were analysed by log-rank test and p-value <0.05 was considered statistically significant.
Results
At CR detection time, 18 patients showed normal HLC ratio, 11 had normal FLC ratio (thus they were in “stringent” CR), and 13 had negative MRD. After a median follow-up of 42 months, 12 patients remain in CR and 13 have relapsed, 11 of whom are deceased. Overall, though neither HLC or FLC assays, nor MRD evaluation, alone or in different combinations, showed a statistically significant influence on the clinical outcome, a trend toward a better PFS (81% vs 50%) was observed in patients with sCR, particularly in those with IgA subtype (100% vs 35%), where normal HLC also identified a subgroup with more favorable outcome (PFS 67% vs 41%). Interestingly, PFS was lower in patients with both abnormal HLC and FLC ratios than in those with only abnormal FLC (40% vs 55%, respectively).
Summary
Our preliminary and still numerically limited experience suggests that HLC might have a prognostic role in patients with IgA MM in CR and might enhance the negative effect of abnormal FLC on PFS estimate. A larger number of patients and an extended follow-up are required for achieving more robust data.
Keyword(s): Multiple myeloma, Prognostic factor
Session topic: Publication Only
Type: Publication Only
Background
The International Myeloma Working Group (IMWG) guidelines recommend the use of protein electrophoresis, serum/urine immunofixation and free light chain (FLC) assay for assessing response to treatment in multiple myeloma (MM). In this setting, flow cytometry (FC) is emerging as a useful, though difficult to standardize, additional tool to detect minimal residual disease (MRD). Furthermore, the novel heavy/light chain (HLC) assay has recently become available to improve quantification of IgG and IgA MM isotypes.
Aims
To evaluate the effect of HLC ratio, FLC ratio and MRD on clinical outcome of MM patients achieving immunofixation negative complete response (CR) after first line therapy, according to IMWG criteria.
Methods
We followed a prospective cohort of 25 patients with MM (14 males, 11 females; median age 63.2, range 43-82; 14 IgG and 11 IgA) who had achieved CR after initial treatments including novel agents, with (n. 11) or without (n. 14) autologous stem cell transplantation (AuSCT). CR was identified after 6 induction cycles in patients not eligible for AuSCT and after AuSCT in those undergoing such a procedure. Sera samples were tested for HLC and FLC ratios by commercially available immunonephelometry kits, while bone marrow samples were analyzed by multiparametric FC for assessing MRD, using a home-made method based on a combination of CD138, CD38, CD56, CD19, CD45, CD20, and CD117 monoclonal antibodies. MRD was defined negative if < 10 neoplastic plasma cells were detected in a 100.000-event file. The Kaplan-Meier method was used to plot and calculate progression free survival (PFS ) and overall survival (OS). Variables were analysed by log-rank test and p-value <0.05 was considered statistically significant.
Results
At CR detection time, 18 patients showed normal HLC ratio, 11 had normal FLC ratio (thus they were in “stringent” CR), and 13 had negative MRD. After a median follow-up of 42 months, 12 patients remain in CR and 13 have relapsed, 11 of whom are deceased. Overall, though neither HLC or FLC assays, nor MRD evaluation, alone or in different combinations, showed a statistically significant influence on the clinical outcome, a trend toward a better PFS (81% vs 50%) was observed in patients with sCR, particularly in those with IgA subtype (100% vs 35%), where normal HLC also identified a subgroup with more favorable outcome (PFS 67% vs 41%). Interestingly, PFS was lower in patients with both abnormal HLC and FLC ratios than in those with only abnormal FLC (40% vs 55%, respectively).
Summary
Our preliminary and still numerically limited experience suggests that HLC might have a prognostic role in patients with IgA MM in CR and might enhance the negative effect of abnormal FLC on PFS estimate. A larger number of patients and an extended follow-up are required for achieving more robust data.
Keyword(s): Multiple myeloma, Prognostic factor
Session topic: Publication Only
Abstract: PB1887
Type: Publication Only
Background
The International Myeloma Working Group (IMWG) guidelines recommend the use of protein electrophoresis, serum/urine immunofixation and free light chain (FLC) assay for assessing response to treatment in multiple myeloma (MM). In this setting, flow cytometry (FC) is emerging as a useful, though difficult to standardize, additional tool to detect minimal residual disease (MRD). Furthermore, the novel heavy/light chain (HLC) assay has recently become available to improve quantification of IgG and IgA MM isotypes.
Aims
To evaluate the effect of HLC ratio, FLC ratio and MRD on clinical outcome of MM patients achieving immunofixation negative complete response (CR) after first line therapy, according to IMWG criteria.
Methods
We followed a prospective cohort of 25 patients with MM (14 males, 11 females; median age 63.2, range 43-82; 14 IgG and 11 IgA) who had achieved CR after initial treatments including novel agents, with (n. 11) or without (n. 14) autologous stem cell transplantation (AuSCT). CR was identified after 6 induction cycles in patients not eligible for AuSCT and after AuSCT in those undergoing such a procedure. Sera samples were tested for HLC and FLC ratios by commercially available immunonephelometry kits, while bone marrow samples were analyzed by multiparametric FC for assessing MRD, using a home-made method based on a combination of CD138, CD38, CD56, CD19, CD45, CD20, and CD117 monoclonal antibodies. MRD was defined negative if < 10 neoplastic plasma cells were detected in a 100.000-event file. The Kaplan-Meier method was used to plot and calculate progression free survival (PFS ) and overall survival (OS). Variables were analysed by log-rank test and p-value <0.05 was considered statistically significant.
Results
At CR detection time, 18 patients showed normal HLC ratio, 11 had normal FLC ratio (thus they were in “stringent” CR), and 13 had negative MRD. After a median follow-up of 42 months, 12 patients remain in CR and 13 have relapsed, 11 of whom are deceased. Overall, though neither HLC or FLC assays, nor MRD evaluation, alone or in different combinations, showed a statistically significant influence on the clinical outcome, a trend toward a better PFS (81% vs 50%) was observed in patients with sCR, particularly in those with IgA subtype (100% vs 35%), where normal HLC also identified a subgroup with more favorable outcome (PFS 67% vs 41%). Interestingly, PFS was lower in patients with both abnormal HLC and FLC ratios than in those with only abnormal FLC (40% vs 55%, respectively).
Summary
Our preliminary and still numerically limited experience suggests that HLC might have a prognostic role in patients with IgA MM in CR and might enhance the negative effect of abnormal FLC on PFS estimate. A larger number of patients and an extended follow-up are required for achieving more robust data.
Keyword(s): Multiple myeloma, Prognostic factor
Session topic: Publication Only
Type: Publication Only
Background
The International Myeloma Working Group (IMWG) guidelines recommend the use of protein electrophoresis, serum/urine immunofixation and free light chain (FLC) assay for assessing response to treatment in multiple myeloma (MM). In this setting, flow cytometry (FC) is emerging as a useful, though difficult to standardize, additional tool to detect minimal residual disease (MRD). Furthermore, the novel heavy/light chain (HLC) assay has recently become available to improve quantification of IgG and IgA MM isotypes.
Aims
To evaluate the effect of HLC ratio, FLC ratio and MRD on clinical outcome of MM patients achieving immunofixation negative complete response (CR) after first line therapy, according to IMWG criteria.
Methods
We followed a prospective cohort of 25 patients with MM (14 males, 11 females; median age 63.2, range 43-82; 14 IgG and 11 IgA) who had achieved CR after initial treatments including novel agents, with (n. 11) or without (n. 14) autologous stem cell transplantation (AuSCT). CR was identified after 6 induction cycles in patients not eligible for AuSCT and after AuSCT in those undergoing such a procedure. Sera samples were tested for HLC and FLC ratios by commercially available immunonephelometry kits, while bone marrow samples were analyzed by multiparametric FC for assessing MRD, using a home-made method based on a combination of CD138, CD38, CD56, CD19, CD45, CD20, and CD117 monoclonal antibodies. MRD was defined negative if < 10 neoplastic plasma cells were detected in a 100.000-event file. The Kaplan-Meier method was used to plot and calculate progression free survival (PFS ) and overall survival (OS). Variables were analysed by log-rank test and p-value <0.05 was considered statistically significant.
Results
At CR detection time, 18 patients showed normal HLC ratio, 11 had normal FLC ratio (thus they were in “stringent” CR), and 13 had negative MRD. After a median follow-up of 42 months, 12 patients remain in CR and 13 have relapsed, 11 of whom are deceased. Overall, though neither HLC or FLC assays, nor MRD evaluation, alone or in different combinations, showed a statistically significant influence on the clinical outcome, a trend toward a better PFS (81% vs 50%) was observed in patients with sCR, particularly in those with IgA subtype (100% vs 35%), where normal HLC also identified a subgroup with more favorable outcome (PFS 67% vs 41%). Interestingly, PFS was lower in patients with both abnormal HLC and FLC ratios than in those with only abnormal FLC (40% vs 55%, respectively).
Summary
Our preliminary and still numerically limited experience suggests that HLC might have a prognostic role in patients with IgA MM in CR and might enhance the negative effect of abnormal FLC on PFS estimate. A larger number of patients and an extended follow-up are required for achieving more robust data.
Keyword(s): Multiple myeloma, Prognostic factor
Session topic: Publication Only
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