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Evaluating the use of Multiparametric Flow Cytometry in establishing the presence of Minimal Residual Disease in systemic AL amyloidosis: a report of eight patients
Abstracts PO-178
PO-179
Evaluating the use of Multiparametric Flow Cytometry in establishing the presence of Minimal Residual Disease in systemic AL amyloidosis: a report of eight patients
Hospitalization Rates for Newly Diagnosed Multiple Myeloma Patients in the United States Medicare Database
M. Coyne, A. Baginska, D. Rowczenio, A.D. Wechalekar
A.A. Yusuf,1,2 T. Bovitz,1 W. Werther,3 D. Felici,3 M. Mahue,3 K. Bridges,3 Y. Peng1 1
Chronic Disease Research Group, Minneapolis, MN, USA; 2Univer-
National Amyloidosis Centre, University College London Medical
sity of Minnesota, Minneapolis, MN, USA; 3Onyx Pharmaceuticals
School, Royal Free Campus, London, UK
Inc., an Amgen Subsidiary, South San Francisco, CA, USA
The identification of Minimal Residual Disease (MRD) is becoming increasingly important for defining outcomes in haematological malignancies; particularly in independently predicting prognosis in myeloma. The role of MRD analysis in systemic AL amyloidosis is less well established. Patients with systemic AL amyloidosis at diagnosis have a lower clonal burden than that seen in myeloma. Moreover, upfront autologous transplantation even in the era of novel therapies continues to provide a more durable remission than that seen in myeloma. Here, as a proof of principle, eight patients with systemic AL amyloidosis in complete response (CR) underwent MRD analysis. MRD analysis was completed if CR was achieved, usually six months from induction treatment. Induction treatments included two patients treated with cyclophosphamide, thalidomide, dexamethasone and six patients with cyclophosphamide, bortezomib and dexamethasone. Two of the six patients that had received CVD based treatment underwent consolidation autologous transplantation. Bone marrow samples were immunophenotyped with eightcolour multiparametric flow cytometry (MFC). The expression of CD138 and CD38 was used to gate the plasma cell population. Patients were identified as having residual disease if a discreet population of phenotypically aberrant plasma cells comprising 50 events were identified in the 500, 000 event file (0.01% limit of detection). An aberrant phenotype was defined as a lack of CD19 expression, strong CD138 expression, weak CD27 expression, and or weak CD45 expression. Interestingly, none of the eight patients demonstrated MRD negativity. All patients demonstrated a measurable clone despite evidence of CR, including two patients who had an autologous bone marrow transplantation. CD117 and CD81 expression failed to provide any additional discrimination between polyclonal and clonal plasma cells. Moreover, the spread between CD81 positive and negative populations was difficult to distinguish in certain patients. In conclusion, this proof of principle study supports MFC as an effective measurement of MRD in patients with systemic AL amyloidosis. The finding that all patients demonstrate MRD positivity raises difficulties in rationalizing if MRD negativity is necessary for a durable remission in systemic AL amyloidosis. To address this further, an adequately powered study randomizing MRD positive patients to further treatment or no treatment may be necessary.
Background: Hospitalization during multiple myeloma (MM) care has not been described in the Medicare population. Medicare is the federal health insurance program for people who are 65+ years, have certain disabilities, or have End-Stage Renal Disease in the United States. We examined the incidence of hospitalization and the cumulative number of hospital days in newly diagnosed (ND) MM Medicare patients (pts). Methods: Using Medicare 20% data (2008-2010), we created a cohort of adult (18 years) NDMM pts. Index year was the calendar year of MM diagnosis after a 12 month period of no MM diagnoses. We created a treated cohort of pts who initiated MM therapy within 1 year of diagnosis. MM therapy included anti-myeloma regimens recommended in the National Comprehensive Cancer Network Guidelines. Percent of pts with hospitalizations in the first year of diagnosis, incidence rates of first hospitalization (per 100 person years (PY)), and cumulative mean, standard deviation (SD), and median number of hospital days were examined for the NDMM and the treated cohorts. Results: We identified 4245 NDMM pts of whom 2173 (51.2%) were treated in the first year following MM diagnosis. The NDMM cohort was 56% female, 76% white, and 92% aged 65+ years. 2765 (65.1%) of the NDMM pts were hospitalized in the first year with an incidence rate of 151.8/100 PY, and a mean (SD) and median cumulative hospital days of 19.3 (19.3) and 13.0, respectively. Among NDMM pts with 2008, 2009, and 2010 index dates, rates of first hospitalization were 143.7, 156.5, 155.7/100 PY, respectively. In the treated cohort, 1565 (72.0%) were hospitalized in the first year with an incidence rate of 176.7/100 PY, and a mean (SD) and median cumulative hospital days of 20.4 (18.7) and 15.0, respectively. In the treated pts with 2008, 2009, and 2010 index dates, rates of first hospitalization were 173.2, 176.0, and 180.8/100 PY, respectively. Hospitalization rates were higher in treated pts with a history of atherosclerotic heart disease (ASHD) (Chi-square¼36.4, p¼<0.001) and chronic kidney disease (CKD) (Chi-square ¼19.7, p<0.001), when compared to those without these conditions. Conclusions: Most NDMM pts are hospitalized in the first year with higher rates in treated pts. There was an increase in hospitalizations in treated pts with ASHD, CKD, and over the 3 year period. Additional analyses are warranted to understand the relationship between treatments, comorbid conditions, and hospitalization.
15th International Myeloma Workshop, September 23-26, 2015
- e185
PO-179
Evaluating the use of Multiparametric Flow Cytometry in establishing the presence of Minimal Residual Disease in systemic AL amyloidosis: a report of eight patients
Hospitalization Rates for Newly Diagnosed Multiple Myeloma Patients in the United States Medicare Database
M. Coyne, A. Baginska, D. Rowczenio, A.D. Wechalekar
A.A. Yusuf,1,2 T. Bovitz,1 W. Werther,3 D. Felici,3 M. Mahue,3 K. Bridges,3 Y. Peng1 1
Chronic Disease Research Group, Minneapolis, MN, USA; 2Univer-
National Amyloidosis Centre, University College London Medical
sity of Minnesota, Minneapolis, MN, USA; 3Onyx Pharmaceuticals
School, Royal Free Campus, London, UK
Inc., an Amgen Subsidiary, South San Francisco, CA, USA
The identification of Minimal Residual Disease (MRD) is becoming increasingly important for defining outcomes in haematological malignancies; particularly in independently predicting prognosis in myeloma. The role of MRD analysis in systemic AL amyloidosis is less well established. Patients with systemic AL amyloidosis at diagnosis have a lower clonal burden than that seen in myeloma. Moreover, upfront autologous transplantation even in the era of novel therapies continues to provide a more durable remission than that seen in myeloma. Here, as a proof of principle, eight patients with systemic AL amyloidosis in complete response (CR) underwent MRD analysis. MRD analysis was completed if CR was achieved, usually six months from induction treatment. Induction treatments included two patients treated with cyclophosphamide, thalidomide, dexamethasone and six patients with cyclophosphamide, bortezomib and dexamethasone. Two of the six patients that had received CVD based treatment underwent consolidation autologous transplantation. Bone marrow samples were immunophenotyped with eightcolour multiparametric flow cytometry (MFC). The expression of CD138 and CD38 was used to gate the plasma cell population. Patients were identified as having residual disease if a discreet population of phenotypically aberrant plasma cells comprising 50 events were identified in the 500, 000 event file (0.01% limit of detection). An aberrant phenotype was defined as a lack of CD19 expression, strong CD138 expression, weak CD27 expression, and or weak CD45 expression. Interestingly, none of the eight patients demonstrated MRD negativity. All patients demonstrated a measurable clone despite evidence of CR, including two patients who had an autologous bone marrow transplantation. CD117 and CD81 expression failed to provide any additional discrimination between polyclonal and clonal plasma cells. Moreover, the spread between CD81 positive and negative populations was difficult to distinguish in certain patients. In conclusion, this proof of principle study supports MFC as an effective measurement of MRD in patients with systemic AL amyloidosis. The finding that all patients demonstrate MRD positivity raises difficulties in rationalizing if MRD negativity is necessary for a durable remission in systemic AL amyloidosis. To address this further, an adequately powered study randomizing MRD positive patients to further treatment or no treatment may be necessary.
Background: Hospitalization during multiple myeloma (MM) care has not been described in the Medicare population. Medicare is the federal health insurance program for people who are 65+ years, have certain disabilities, or have End-Stage Renal Disease in the United States. We examined the incidence of hospitalization and the cumulative number of hospital days in newly diagnosed (ND) MM Medicare patients (pts). Methods: Using Medicare 20% data (2008-2010), we created a cohort of adult (18 years) NDMM pts. Index year was the calendar year of MM diagnosis after a 12 month period of no MM diagnoses. We created a treated cohort of pts who initiated MM therapy within 1 year of diagnosis. MM therapy included anti-myeloma regimens recommended in the National Comprehensive Cancer Network Guidelines. Percent of pts with hospitalizations in the first year of diagnosis, incidence rates of first hospitalization (per 100 person years (PY)), and cumulative mean, standard deviation (SD), and median number of hospital days were examined for the NDMM and the treated cohorts. Results: We identified 4245 NDMM pts of whom 2173 (51.2%) were treated in the first year following MM diagnosis. The NDMM cohort was 56% female, 76% white, and 92% aged 65+ years. 2765 (65.1%) of the NDMM pts were hospitalized in the first year with an incidence rate of 151.8/100 PY, and a mean (SD) and median cumulative hospital days of 19.3 (19.3) and 13.0, respectively. Among NDMM pts with 2008, 2009, and 2010 index dates, rates of first hospitalization were 143.7, 156.5, 155.7/100 PY, respectively. In the treated cohort, 1565 (72.0%) were hospitalized in the first year with an incidence rate of 176.7/100 PY, and a mean (SD) and median cumulative hospital days of 20.4 (18.7) and 15.0, respectively. In the treated pts with 2008, 2009, and 2010 index dates, rates of first hospitalization were 173.2, 176.0, and 180.8/100 PY, respectively. Hospitalization rates were higher in treated pts with a history of atherosclerotic heart disease (ASHD) (Chi-square¼36.4, p¼<0.001) and chronic kidney disease (CKD) (Chi-square ¼19.7, p<0.001), when compared to those without these conditions. Conclusions: Most NDMM pts are hospitalized in the first year with higher rates in treated pts. There was an increase in hospitalizations in treated pts with ASHD, CKD, and over the 3 year period. Additional analyses are warranted to understand the relationship between treatments, comorbid conditions, and hospitalization.
15th International Myeloma Workshop, September 23-26, 2015
- e185