- Email: [email protected]
Revised International Staging System applied to Japanese patients: A multicenter retrospective collaborative study of the Japanese Society of Myeloma
Abstracts International Staging System (ISS) score. MYC oncogene has a pivotal role in cell growth and proliferation, but the prognostic impact of MYC activation in MM is not fully covered. MYC activa:tion is reported in 10-67% with MM depending on the method used e.g. karyotyping, fluorescence in situ hybridisation (FISH) or gene expression analysis. A commercial myc antibody is now available, which makes myc protein expression easy to detect. The aim of this study was to describe clinicopathological features and prognostic impact of myc protein expression in MM. Materials and methods: We retrospectively analysed bone marrow samples from 193 newly diagnosed, untreated patients diagnosed with MM between January 1st 2006 and June 30th 2010 in the Region of Southern Denmark. Clinicopathological, karyotyping and FISH data was collected. Myc protein expression was assessed using immunohistochemical double staining for the plasma cell marker CD138 and myc. Results: Myc protein was expressed in 177 cases (92%) with a range of 1-65% myc-positive plasma cells. Twentynine patients (15%) had smouldering myeloma at time of diagnosis. Among these only two (7%) had 10% myc-positive plasma cells compared to 44% of symptomatic MM (p¼0.001). Survival analyses were made among 165 patients receiving antimyeloma treatment and showed significantly inferior overall survival (OS) with myc protein expression 40% (p<0.001). Fifteen of 165 patients (9%) had myc protein 40%, and this significantly correlated with high proliferation index (p<0.01), high percentage of plasma cell infiltration in bone marrow (p<0.001), plasmablastic morphology (p<0.001) and abnormal karyotype (p<0.001), but not with adverse cytogenetics identified by FISH. There was a trend towards correlation with high ISS score (p¼0.06). In multivariate Cox survival analysis myc protein expression 40% was independently associated with poor prognosis with a hazard ratio of 2.6. Conclusion: High myeloma cell expression of myc protein is a feature of aggressive disease and a strong prognostic marker in MM.
PO-012 Morning urine as an alternative to 24-hour urine electrophoresis? Renal lesions assessment, monoclonal peak detection and quantification comparisons
e88
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collected separately in a small flask. Both urine types from all patients were analyzed on Hydragel Urine Profile (UP) (Sebia, Lisses) on Hydrasys 2 Scan instrument. Urine peak quantification was performed after scanning the ELP track of the UP gel. The percentage of concordance between morning and 24h urine was calculated for renal lesion typing and for monoclonal component typing. Results: Hydragel UP kit allows, with a single analysis, to screen proteinuria content, type renal lesions, type and quantify monoclonal components. Among the 284 patients we analyzed, 58 presented a monoclonal component. We obtained an excellent concordance (98.6%) between morning and 24h urines for proteinuria typing (physiological, glomerular, tubular, mixed and overload proteinuria). For monoclonal component typing, an excellent concordance was observed as well (98.9%). Urine peaks at the limit of the technique detection from only 3 patients were picked up only by one of the two urine collection types (2 picked up on morning urine only and 1 picked up on 24h urine only). As for peak quantification, we observed a very good correlation between the two urine collection types on the tested range. Conclusion: To our knowledge, no study has compared morning to 24h urine analysis for such number of patients and for proteinuria typing, monoclonal component detection, typing and quantification. Our results clearly show that morning urine is a good candidate to replace 24h urines for detection and quantification of urine peak, as well as for renal lesion typing. Before switching to morning urine, further studies are needed to confirm these findings. Comparisons in the context of patient follow up are still lacking.
PO-013 Revised International Staging System applied to Japanese patients: A multicenter retrospective collaborative study of the Japanese Society of Myeloma S. K. Y. E.
Ozaki, T. Saitoh, H. Handa, H. Murakami, Suzuki, N. Takezako, J. Konishi, K. Sunami, Kuroda, M. Itagaki, H. Asaoku, K. Shimizu, Nagura
Department of Hematology, Tokushima Prefectural Central Hospital;
P. Boulard
Department of Laboratory Sciences, Graduate School of Health
Evolab, Thionville, France
Sciences, Gunma University; Department of Hematology, Gunma University; Department of Hematology, Japanese Red Cross Medical
Background: Urine protein electrophoresis (UPE) and immunofixation (uIF) are central in the diagnosis and follow up of patients with monoclonal gammopathies. They allow: proteinuria screening, urine peak typing and quantification. Peak quantification is an important criterion used for response to treatment assessment for multiple myeloma patients. International Myeloma Working Group (IMWG) guidelines recommend 24 hour (24h) urine testing. In front of difficulties of 24h urine collection, and since proof of analyzes on morning urine is lacking, we decided to compare data from both morning and 24h urines. Methods: 24h urine collection was done for 284 patients with morning urine
Center; Division of Hematology, National Hospital Organization
15th International Myeloma Workshop, September 23-26, 2015
Disaster Medical Center; Department of Hematology, National Hospital Organization Okayama Medical Center; Department of Hematology, Hiroshima University Hospital; Department of Hematology, Hiroshima Red Cross Hospital; Department of Hematology, Tokai Central Hospital; Department of Hematology, Chutoen General Medical Center
Survival outcomes of patients with multiple myeloma (MM) are quite heterogeneous because of the risk factors such as stage and cytogenetic abnormalities. Until recently, International Staging
Abstracts System (ISS) has been widely used as a prognostic model, but its validity has not been clarified in the era of novel agents. Recently, a Revised ISS model (R-ISS) incorporating serum LDH abnormality and chromosomal abnormalities represented by [t(4;14), t(14;16), or del(17p)] in addition to the original ISS definition has been proposed (Oliva S, et al. EHA 2014, #S1289). The Japanese Society of Myeloma reviewed the clinical features of Japanese MM patients diagnosed between 2001 and 2012, and evaluated the clinical relevance of the R-ISS. Clinical data of 3270 patients were collected from 38 centers, and among them ISS and R-ISS analysis were applicable to 2998 and 788 patients, respectively. Patient characteristics such as age, sex, type of M protein, Durie and Salmon stage, ISS stage, and chromosomal abnormalities were not significantly different between the groups of ISS and R-ISS. In the 788 patients evaluable for the R-ISS, the distribution of the patients according to ISS stages I, II, and III were 31.4%, 35.8%, and 32.8%, respectively, whereas that of R-ISS stages were 22.2%, 67.6%, and 10.2%, respectively. Median overall survival (OS) for the stages I, II, and III of the ISS and those of the R-ISS were 100.7, 65.2, 50.9 months and 152.8, 62.4, 40.5 months, respectively. Thus, the R-ISS model was identified as a more clearly discriminating model between patients with good and poor prognosis compared with the ISS model. According to the ISS analysis, there were no significant differences in the median OS between patients initially treated with novel agents and those treated with conventional chemotherapy (stage I, not reached vs 87.6 months, p¼0.054; stage II, 71.2 vs 58.5 months, p¼0.18; and stage III, 73.8 vs 48.8 months, p¼0.24). In contrast, the RISS analysis clearly showed a beneficial effect of novel therapy compared with conventional chemotherapy (stage I, not reached vs 87.6 months, p¼0.017; stage II, 78.8 vs 61.7 months, p¼0.075; and 37.5 vs 45.3 months, p¼0.87). Multivariate analysis for OS also confirmed the prognostic relevance of the R-ISS stage III (p¼0.006) but not ISS stage III (p¼0.692). Accordingly, our results would implicate that R-ISS is a useful model for the risk assessment in the era of novel agents in Japanese patients with MM.
(BMI) has been found to correlate positively with the risk of developing multiple myeloma (MM). The influence of body fat composition on incidence, treatment response and overall prognosis of MM patients has not been investigated yet. Patients and Methods: A subgroup of 108 patients enrolled in the GMMG-MM5 trial (Randomized phase III trial for previously untreated MM to evaluate two regimens of bortezomib based induction therapy and lenalidomide consolidation followed by lenalidomide maintenance treatment), who received a whole body computed tomography (wb-CT) before induction therapy, were included in this retrospective study. Body fat composition was measured in wb-CT for each patient, divided in the compartments abdomen, pelvis, thigh and further categorized in subcutaneous (SAT) and visceral adipose tissue (VAT). The correlation of these parameters with disease activity (M protein, plasma cell count, LDH) including CRAB-criteria, adverse cytogenetics, treatment response, and adverse events (infection and leukopenia) were statistically evaluated. Results: A significant correlation was observed between VAT of the abdomen (p¼0.03) and pelvis (p¼0.035) and treatment response (42 patients with very good partial response or better and 55 patients with partial response or worse). Furthermore, a significant negative correlation was found between adverse cytogenetics and VAT of the abdomen and pelvis, respectively (del 13q14: p¼0.036 and n.s.; gain 1q21: p¼0.009 and p¼0.021; t(4;14): p¼0.038 and p¼0.042). Del 17p13 was identified but due to the low number of positive patients it could not be further investigated in this context. The correlation of VAT and SAT with adverse events was not statistically significant. The BMI did not show a significant correlation with treatment response and investigated cytogenetics. Conclusion: Based on the clinically relevant difference in treatment outcome depending on VAT in our study, excessive body fat of abdomen and pelvis might be a predictive factor for poor treatment response. Further influences in this context might be considered as well, e.g. Chemotherapy dosing and metabolism of body fat. Further studies including the development of weight gain or loss over time relating to the course of disease and therapy are necessary to facilitate this hypothesis.
PO-015 PO-014 Body fat percentage and distribution as predictive factors for treatment response e a retrospective study in patients with symptomatic multiple myeloma J. Gross,2 J. Nattenmüller,1 H. Goldschmidt,2 S. Delorme,3 M. Merz,2 J. Hillengass2 1
Department of Diagnostic and Interventional Radiology, University
Heavy/Light Chain Analysis for Response Monitoring in Multiple Myeloma Patients: Comparisons With Immunofixation, Serum Free Light Chain, and Multicolor Flow-Cytometry Analysis K. Matsue,1 Y. Suehara,1 K. Fukumoto,1 M. Fujisawa,1 M. Takeuchi,1 H. Sugihara,1 H. Takamatsu,2 K. Endean3
Hospital Heidelberg, Heidelberg, Germany; 2Department of Hema-
1
tology and Oncology, University Hospital of Heidelberg, Heidelberg, Germany; 3Department of Radiology, German Cancer Research
gawa-shi, Japan; 2Cellular Transplantation Biology, Kanazawa Uni-
Center, Heidelberg, Germany
Birmingham, United Kingdom
Introduction/Background: Obesity is a well-known risk factor for the occurrence of malignant tumors. An increased body mass index
Background: Monitoring of MM patients is required to assess and determine treatment response. There are limited data available
Division of Hematology/Oncology, Kameda Medical Center, Kamo-
versity Hospital, Kanazawa, Japan; 3The Binding Site Ltd,
15th International Myeloma Workshop, September 23-26, 2015
- e89
PO-012 Morning urine as an alternative to 24-hour urine electrophoresis? Renal lesions assessment, monoclonal peak detection and quantification comparisons
e88
-
collected separately in a small flask. Both urine types from all patients were analyzed on Hydragel Urine Profile (UP) (Sebia, Lisses) on Hydrasys 2 Scan instrument. Urine peak quantification was performed after scanning the ELP track of the UP gel. The percentage of concordance between morning and 24h urine was calculated for renal lesion typing and for monoclonal component typing. Results: Hydragel UP kit allows, with a single analysis, to screen proteinuria content, type renal lesions, type and quantify monoclonal components. Among the 284 patients we analyzed, 58 presented a monoclonal component. We obtained an excellent concordance (98.6%) between morning and 24h urines for proteinuria typing (physiological, glomerular, tubular, mixed and overload proteinuria). For monoclonal component typing, an excellent concordance was observed as well (98.9%). Urine peaks at the limit of the technique detection from only 3 patients were picked up only by one of the two urine collection types (2 picked up on morning urine only and 1 picked up on 24h urine only). As for peak quantification, we observed a very good correlation between the two urine collection types on the tested range. Conclusion: To our knowledge, no study has compared morning to 24h urine analysis for such number of patients and for proteinuria typing, monoclonal component detection, typing and quantification. Our results clearly show that morning urine is a good candidate to replace 24h urines for detection and quantification of urine peak, as well as for renal lesion typing. Before switching to morning urine, further studies are needed to confirm these findings. Comparisons in the context of patient follow up are still lacking.
PO-013 Revised International Staging System applied to Japanese patients: A multicenter retrospective collaborative study of the Japanese Society of Myeloma S. K. Y. E.
Ozaki, T. Saitoh, H. Handa, H. Murakami, Suzuki, N. Takezako, J. Konishi, K. Sunami, Kuroda, M. Itagaki, H. Asaoku, K. Shimizu, Nagura
Department of Hematology, Tokushima Prefectural Central Hospital;
P. Boulard
Department of Laboratory Sciences, Graduate School of Health
Evolab, Thionville, France
Sciences, Gunma University; Department of Hematology, Gunma University; Department of Hematology, Japanese Red Cross Medical
Background: Urine protein electrophoresis (UPE) and immunofixation (uIF) are central in the diagnosis and follow up of patients with monoclonal gammopathies. They allow: proteinuria screening, urine peak typing and quantification. Peak quantification is an important criterion used for response to treatment assessment for multiple myeloma patients. International Myeloma Working Group (IMWG) guidelines recommend 24 hour (24h) urine testing. In front of difficulties of 24h urine collection, and since proof of analyzes on morning urine is lacking, we decided to compare data from both morning and 24h urines. Methods: 24h urine collection was done for 284 patients with morning urine
Center; Division of Hematology, National Hospital Organization
15th International Myeloma Workshop, September 23-26, 2015
Disaster Medical Center; Department of Hematology, National Hospital Organization Okayama Medical Center; Department of Hematology, Hiroshima University Hospital; Department of Hematology, Hiroshima Red Cross Hospital; Department of Hematology, Tokai Central Hospital; Department of Hematology, Chutoen General Medical Center
Survival outcomes of patients with multiple myeloma (MM) are quite heterogeneous because of the risk factors such as stage and cytogenetic abnormalities. Until recently, International Staging
Abstracts System (ISS) has been widely used as a prognostic model, but its validity has not been clarified in the era of novel agents. Recently, a Revised ISS model (R-ISS) incorporating serum LDH abnormality and chromosomal abnormalities represented by [t(4;14), t(14;16), or del(17p)] in addition to the original ISS definition has been proposed (Oliva S, et al. EHA 2014, #S1289). The Japanese Society of Myeloma reviewed the clinical features of Japanese MM patients diagnosed between 2001 and 2012, and evaluated the clinical relevance of the R-ISS. Clinical data of 3270 patients were collected from 38 centers, and among them ISS and R-ISS analysis were applicable to 2998 and 788 patients, respectively. Patient characteristics such as age, sex, type of M protein, Durie and Salmon stage, ISS stage, and chromosomal abnormalities were not significantly different between the groups of ISS and R-ISS. In the 788 patients evaluable for the R-ISS, the distribution of the patients according to ISS stages I, II, and III were 31.4%, 35.8%, and 32.8%, respectively, whereas that of R-ISS stages were 22.2%, 67.6%, and 10.2%, respectively. Median overall survival (OS) for the stages I, II, and III of the ISS and those of the R-ISS were 100.7, 65.2, 50.9 months and 152.8, 62.4, 40.5 months, respectively. Thus, the R-ISS model was identified as a more clearly discriminating model between patients with good and poor prognosis compared with the ISS model. According to the ISS analysis, there were no significant differences in the median OS between patients initially treated with novel agents and those treated with conventional chemotherapy (stage I, not reached vs 87.6 months, p¼0.054; stage II, 71.2 vs 58.5 months, p¼0.18; and stage III, 73.8 vs 48.8 months, p¼0.24). In contrast, the RISS analysis clearly showed a beneficial effect of novel therapy compared with conventional chemotherapy (stage I, not reached vs 87.6 months, p¼0.017; stage II, 78.8 vs 61.7 months, p¼0.075; and 37.5 vs 45.3 months, p¼0.87). Multivariate analysis for OS also confirmed the prognostic relevance of the R-ISS stage III (p¼0.006) but not ISS stage III (p¼0.692). Accordingly, our results would implicate that R-ISS is a useful model for the risk assessment in the era of novel agents in Japanese patients with MM.
(BMI) has been found to correlate positively with the risk of developing multiple myeloma (MM). The influence of body fat composition on incidence, treatment response and overall prognosis of MM patients has not been investigated yet. Patients and Methods: A subgroup of 108 patients enrolled in the GMMG-MM5 trial (Randomized phase III trial for previously untreated MM to evaluate two regimens of bortezomib based induction therapy and lenalidomide consolidation followed by lenalidomide maintenance treatment), who received a whole body computed tomography (wb-CT) before induction therapy, were included in this retrospective study. Body fat composition was measured in wb-CT for each patient, divided in the compartments abdomen, pelvis, thigh and further categorized in subcutaneous (SAT) and visceral adipose tissue (VAT). The correlation of these parameters with disease activity (M protein, plasma cell count, LDH) including CRAB-criteria, adverse cytogenetics, treatment response, and adverse events (infection and leukopenia) were statistically evaluated. Results: A significant correlation was observed between VAT of the abdomen (p¼0.03) and pelvis (p¼0.035) and treatment response (42 patients with very good partial response or better and 55 patients with partial response or worse). Furthermore, a significant negative correlation was found between adverse cytogenetics and VAT of the abdomen and pelvis, respectively (del 13q14: p¼0.036 and n.s.; gain 1q21: p¼0.009 and p¼0.021; t(4;14): p¼0.038 and p¼0.042). Del 17p13 was identified but due to the low number of positive patients it could not be further investigated in this context. The correlation of VAT and SAT with adverse events was not statistically significant. The BMI did not show a significant correlation with treatment response and investigated cytogenetics. Conclusion: Based on the clinically relevant difference in treatment outcome depending on VAT in our study, excessive body fat of abdomen and pelvis might be a predictive factor for poor treatment response. Further influences in this context might be considered as well, e.g. Chemotherapy dosing and metabolism of body fat. Further studies including the development of weight gain or loss over time relating to the course of disease and therapy are necessary to facilitate this hypothesis.
PO-015 PO-014 Body fat percentage and distribution as predictive factors for treatment response e a retrospective study in patients with symptomatic multiple myeloma J. Gross,2 J. Nattenmüller,1 H. Goldschmidt,2 S. Delorme,3 M. Merz,2 J. Hillengass2 1
Department of Diagnostic and Interventional Radiology, University
Heavy/Light Chain Analysis for Response Monitoring in Multiple Myeloma Patients: Comparisons With Immunofixation, Serum Free Light Chain, and Multicolor Flow-Cytometry Analysis K. Matsue,1 Y. Suehara,1 K. Fukumoto,1 M. Fujisawa,1 M. Takeuchi,1 H. Sugihara,1 H. Takamatsu,2 K. Endean3
Hospital Heidelberg, Heidelberg, Germany; 2Department of Hema-
1
tology and Oncology, University Hospital of Heidelberg, Heidelberg, Germany; 3Department of Radiology, German Cancer Research
gawa-shi, Japan; 2Cellular Transplantation Biology, Kanazawa Uni-
Center, Heidelberg, Germany
Birmingham, United Kingdom
Introduction/Background: Obesity is a well-known risk factor for the occurrence of malignant tumors. An increased body mass index
Background: Monitoring of MM patients is required to assess and determine treatment response. There are limited data available
Division of Hematology/Oncology, Kameda Medical Center, Kamo-
versity Hospital, Kanazawa, Japan; 3The Binding Site Ltd,
15th International Myeloma Workshop, September 23-26, 2015
- e89