NEW IMWG COMPARED TO CRAB CRITERIA TO PROPERLY DEFINE START-TIME THERAPY IN MULTIPLE MYELOMA: A RETROSPECTIVE SINGLE-CENTER ANALYSIS OF 180 PATIENTS
(Abstract release date: 05/19/16)
EHA Library. Torti L. 06/09/16; 132870; E1321
Dr. Lorenza Torti
Contributions
Contributions
Abstract
Abstract: E1321
Type: Eposter Presentation
Background
The diagnosis of Multiple Myeloma (MM) traditionally requires the evidence of signs of end-organ damage like hypercalcemia, renal failure, anemia and osteolytic bone lesions,usually referred by the acronym “CRAB”. The International Myeloma Working Group (IMWG) recently updated the criteria for the diagnosis of MM,including biomarkers that are considered myeloma defining events (MDEs).They are: clonal bone marrow plasma cells >60%,serum free light chain (FLC) ratio >100 and the presence of more than one focal lesion on magnetic resonance imaging (MRI).
Aims
In this paper we’d like to share our experience regarding the recent IMWG criteria in a group of 180 newly diagnosed MM patients, to discuss strengths as well as caveats and uncertainties. Ninety were young and treated with transplant procedure and ninety were old (more than 65-year-old)and were treated with different regimens,including new drugs.
Methods
We performed a retrospective analysis of these MM cases with MDEs diagnosed from 1999 to 2014 in our Department, comparing traditional CRAB versus recent IMWG criteria. We retrospectively looked for the new defining characteristics published by Rajkumar (Lancet Oncol 2014) during the disease course before both the development of CRAB events and beginning of treatment.
Results
We found the occurrence of IMWG new criteria before clear manifestation of the CRAB markers in thirty-eight patients (21% of total). In particular the majority of this group has shown a FLC ratio>100 (14% of total),5% presented injuries detected by MRI and only 2% had a bone marrow plasma cells involvement >60%. Most of them (92%) were followed by development of CRAB features after a medium time of seven months (range 3-15) and progressed to active MM requiring therapy in less than one year. In the category of patients carrying the new criteria 71% were old (median age 70 years, range 53-89), 29% were young.Of them 56% had IgG MM, 26% IgA MM, 18% micromolecular MM; prevalent light chain was kappa (65%). The majority of these cases (76%) had a previous history of MGUS and smouldering MM. Only two patients among 180 started therapy not according to classic criteria, but on new IMWG biomarkers, associated with deterioration of clinical condition and increase in monoclonal component. However three young patients presented new IMWG events associated with a stable monoclonal protein, good clinical status. Clinical judgement was most important in this setting, as we decided not to start therapy and to maintain close follow-up. In our view it is likely that earlier treatment of these patients would not be beneficial,but might instead result in greater toxicity. On the other hand patients without IMWG 2014 preceding CRAB criteria,often identify a high-risk subgroup with a severe and faster biological behavior. The largest part of them indeed (57%) presented markers of aggressive biological profile like IgD paraprotein, extramedullary involvement or unfavorable cytogenetic abnormalities such as deletion of chromosome 17. Probably a well defined temporal difference between development of new IMWG and the old CRAB characteristics could be present only for intermediate-risk MM patients with a slower kinetics of disease. In most high-risk patients probably new IMWG and CRAB markers present all together simultaneously.
Conclusion
Our single-center study confirms the pivotal role of new IMWG criteria to optimize management of patients with smouldering MM and to antedate start-time of effective treatment before end-organ damage, expecially for elderly patients.In our experience the most powerful biomarker of progression is FLC ratio>100. Neverthless particular caution should be used in youth patients to avoid too much toxicity of a earlier intervention,that can also lead to selection of fitter clone and accelerated progression.Finally these new biomarkers should be critically validated prospectively in future clinical trials to allow an early treatment in patients without CRAB features with high-risk markers.
Session topic: E-poster
Keyword(s): Diagnosis, Multiple myeloma, Smoldering, Therapy
Type: Eposter Presentation
Background
The diagnosis of Multiple Myeloma (MM) traditionally requires the evidence of signs of end-organ damage like hypercalcemia, renal failure, anemia and osteolytic bone lesions,usually referred by the acronym “CRAB”. The International Myeloma Working Group (IMWG) recently updated the criteria for the diagnosis of MM,including biomarkers that are considered myeloma defining events (MDEs).They are: clonal bone marrow plasma cells >60%,serum free light chain (FLC) ratio >100 and the presence of more than one focal lesion on magnetic resonance imaging (MRI).
Aims
In this paper we’d like to share our experience regarding the recent IMWG criteria in a group of 180 newly diagnosed MM patients, to discuss strengths as well as caveats and uncertainties. Ninety were young and treated with transplant procedure and ninety were old (more than 65-year-old)and were treated with different regimens,including new drugs.
Methods
We performed a retrospective analysis of these MM cases with MDEs diagnosed from 1999 to 2014 in our Department, comparing traditional CRAB versus recent IMWG criteria. We retrospectively looked for the new defining characteristics published by Rajkumar (Lancet Oncol 2014) during the disease course before both the development of CRAB events and beginning of treatment.
Results
We found the occurrence of IMWG new criteria before clear manifestation of the CRAB markers in thirty-eight patients (21% of total). In particular the majority of this group has shown a FLC ratio>100 (14% of total),5% presented injuries detected by MRI and only 2% had a bone marrow plasma cells involvement >60%. Most of them (92%) were followed by development of CRAB features after a medium time of seven months (range 3-15) and progressed to active MM requiring therapy in less than one year. In the category of patients carrying the new criteria 71% were old (median age 70 years, range 53-89), 29% were young.Of them 56% had IgG MM, 26% IgA MM, 18% micromolecular MM; prevalent light chain was kappa (65%). The majority of these cases (76%) had a previous history of MGUS and smouldering MM. Only two patients among 180 started therapy not according to classic criteria, but on new IMWG biomarkers, associated with deterioration of clinical condition and increase in monoclonal component. However three young patients presented new IMWG events associated with a stable monoclonal protein, good clinical status. Clinical judgement was most important in this setting, as we decided not to start therapy and to maintain close follow-up. In our view it is likely that earlier treatment of these patients would not be beneficial,but might instead result in greater toxicity. On the other hand patients without IMWG 2014 preceding CRAB criteria,often identify a high-risk subgroup with a severe and faster biological behavior. The largest part of them indeed (57%) presented markers of aggressive biological profile like IgD paraprotein, extramedullary involvement or unfavorable cytogenetic abnormalities such as deletion of chromosome 17. Probably a well defined temporal difference between development of new IMWG and the old CRAB characteristics could be present only for intermediate-risk MM patients with a slower kinetics of disease. In most high-risk patients probably new IMWG and CRAB markers present all together simultaneously.
Conclusion
Our single-center study confirms the pivotal role of new IMWG criteria to optimize management of patients with smouldering MM and to antedate start-time of effective treatment before end-organ damage, expecially for elderly patients.In our experience the most powerful biomarker of progression is FLC ratio>100. Neverthless particular caution should be used in youth patients to avoid too much toxicity of a earlier intervention,that can also lead to selection of fitter clone and accelerated progression.Finally these new biomarkers should be critically validated prospectively in future clinical trials to allow an early treatment in patients without CRAB features with high-risk markers.
Session topic: E-poster
Keyword(s): Diagnosis, Multiple myeloma, Smoldering, Therapy
Abstract: E1321
Type: Eposter Presentation
Background
The diagnosis of Multiple Myeloma (MM) traditionally requires the evidence of signs of end-organ damage like hypercalcemia, renal failure, anemia and osteolytic bone lesions,usually referred by the acronym “CRAB”. The International Myeloma Working Group (IMWG) recently updated the criteria for the diagnosis of MM,including biomarkers that are considered myeloma defining events (MDEs).They are: clonal bone marrow plasma cells >60%,serum free light chain (FLC) ratio >100 and the presence of more than one focal lesion on magnetic resonance imaging (MRI).
Aims
In this paper we’d like to share our experience regarding the recent IMWG criteria in a group of 180 newly diagnosed MM patients, to discuss strengths as well as caveats and uncertainties. Ninety were young and treated with transplant procedure and ninety were old (more than 65-year-old)and were treated with different regimens,including new drugs.
Methods
We performed a retrospective analysis of these MM cases with MDEs diagnosed from 1999 to 2014 in our Department, comparing traditional CRAB versus recent IMWG criteria. We retrospectively looked for the new defining characteristics published by Rajkumar (Lancet Oncol 2014) during the disease course before both the development of CRAB events and beginning of treatment.
Results
We found the occurrence of IMWG new criteria before clear manifestation of the CRAB markers in thirty-eight patients (21% of total). In particular the majority of this group has shown a FLC ratio>100 (14% of total),5% presented injuries detected by MRI and only 2% had a bone marrow plasma cells involvement >60%. Most of them (92%) were followed by development of CRAB features after a medium time of seven months (range 3-15) and progressed to active MM requiring therapy in less than one year. In the category of patients carrying the new criteria 71% were old (median age 70 years, range 53-89), 29% were young.Of them 56% had IgG MM, 26% IgA MM, 18% micromolecular MM; prevalent light chain was kappa (65%). The majority of these cases (76%) had a previous history of MGUS and smouldering MM. Only two patients among 180 started therapy not according to classic criteria, but on new IMWG biomarkers, associated with deterioration of clinical condition and increase in monoclonal component. However three young patients presented new IMWG events associated with a stable monoclonal protein, good clinical status. Clinical judgement was most important in this setting, as we decided not to start therapy and to maintain close follow-up. In our view it is likely that earlier treatment of these patients would not be beneficial,but might instead result in greater toxicity. On the other hand patients without IMWG 2014 preceding CRAB criteria,often identify a high-risk subgroup with a severe and faster biological behavior. The largest part of them indeed (57%) presented markers of aggressive biological profile like IgD paraprotein, extramedullary involvement or unfavorable cytogenetic abnormalities such as deletion of chromosome 17. Probably a well defined temporal difference between development of new IMWG and the old CRAB characteristics could be present only for intermediate-risk MM patients with a slower kinetics of disease. In most high-risk patients probably new IMWG and CRAB markers present all together simultaneously.
Conclusion
Our single-center study confirms the pivotal role of new IMWG criteria to optimize management of patients with smouldering MM and to antedate start-time of effective treatment before end-organ damage, expecially for elderly patients.In our experience the most powerful biomarker of progression is FLC ratio>100. Neverthless particular caution should be used in youth patients to avoid too much toxicity of a earlier intervention,that can also lead to selection of fitter clone and accelerated progression.Finally these new biomarkers should be critically validated prospectively in future clinical trials to allow an early treatment in patients without CRAB features with high-risk markers.
Session topic: E-poster
Keyword(s): Diagnosis, Multiple myeloma, Smoldering, Therapy
Type: Eposter Presentation
Background
The diagnosis of Multiple Myeloma (MM) traditionally requires the evidence of signs of end-organ damage like hypercalcemia, renal failure, anemia and osteolytic bone lesions,usually referred by the acronym “CRAB”. The International Myeloma Working Group (IMWG) recently updated the criteria for the diagnosis of MM,including biomarkers that are considered myeloma defining events (MDEs).They are: clonal bone marrow plasma cells >60%,serum free light chain (FLC) ratio >100 and the presence of more than one focal lesion on magnetic resonance imaging (MRI).
Aims
In this paper we’d like to share our experience regarding the recent IMWG criteria in a group of 180 newly diagnosed MM patients, to discuss strengths as well as caveats and uncertainties. Ninety were young and treated with transplant procedure and ninety were old (more than 65-year-old)and were treated with different regimens,including new drugs.
Methods
We performed a retrospective analysis of these MM cases with MDEs diagnosed from 1999 to 2014 in our Department, comparing traditional CRAB versus recent IMWG criteria. We retrospectively looked for the new defining characteristics published by Rajkumar (Lancet Oncol 2014) during the disease course before both the development of CRAB events and beginning of treatment.
Results
We found the occurrence of IMWG new criteria before clear manifestation of the CRAB markers in thirty-eight patients (21% of total). In particular the majority of this group has shown a FLC ratio>100 (14% of total),5% presented injuries detected by MRI and only 2% had a bone marrow plasma cells involvement >60%. Most of them (92%) were followed by development of CRAB features after a medium time of seven months (range 3-15) and progressed to active MM requiring therapy in less than one year. In the category of patients carrying the new criteria 71% were old (median age 70 years, range 53-89), 29% were young.Of them 56% had IgG MM, 26% IgA MM, 18% micromolecular MM; prevalent light chain was kappa (65%). The majority of these cases (76%) had a previous history of MGUS and smouldering MM. Only two patients among 180 started therapy not according to classic criteria, but on new IMWG biomarkers, associated with deterioration of clinical condition and increase in monoclonal component. However three young patients presented new IMWG events associated with a stable monoclonal protein, good clinical status. Clinical judgement was most important in this setting, as we decided not to start therapy and to maintain close follow-up. In our view it is likely that earlier treatment of these patients would not be beneficial,but might instead result in greater toxicity. On the other hand patients without IMWG 2014 preceding CRAB criteria,often identify a high-risk subgroup with a severe and faster biological behavior. The largest part of them indeed (57%) presented markers of aggressive biological profile like IgD paraprotein, extramedullary involvement or unfavorable cytogenetic abnormalities such as deletion of chromosome 17. Probably a well defined temporal difference between development of new IMWG and the old CRAB characteristics could be present only for intermediate-risk MM patients with a slower kinetics of disease. In most high-risk patients probably new IMWG and CRAB markers present all together simultaneously.
Conclusion
Our single-center study confirms the pivotal role of new IMWG criteria to optimize management of patients with smouldering MM and to antedate start-time of effective treatment before end-organ damage, expecially for elderly patients.In our experience the most powerful biomarker of progression is FLC ratio>100. Neverthless particular caution should be used in youth patients to avoid too much toxicity of a earlier intervention,that can also lead to selection of fitter clone and accelerated progression.Finally these new biomarkers should be critically validated prospectively in future clinical trials to allow an early treatment in patients without CRAB features with high-risk markers.
Session topic: E-poster
Keyword(s): Diagnosis, Multiple myeloma, Smoldering, Therapy
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