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201 IRON CHELATION IN TRANSFUSION DEPENDENT MDS PATIENTS – A SINGLE CENTRE EXPERIENCE
S100
Poster Presentations – 13th International Symposium on Myelodyspastic Syndromes / Leukemia Research 39 S1 (2015) S1–S166
marrow blast percentage was >10% in 72% of patients; median 19% (range 1.2-98) Karyotypes were normal in 44%, intermediate risk in 27% and poor risk in 29%. Azacitidine was used as single agent as first line therapy with no prior cytoreduction in all patients. Patients started treatment a median of 2.3 months following diagnosis. Marrow response was assessed after the 6th cycle. Treatment was continued until progression in all cases. A median number of 8 cycles were administered. Marrow assessments were available in 16 patients. Responses were documented in 6 patients, of which 1 was complete and 5 were partial. Stable disease at time of assessment was seen in 4 patients and progression in 6. Transfusion independence was achieved in 8 of 10 patients who were previously transfusion-dependent. Four patients only received 1 cycle of treatment due to progression in 3 and pneumonia in one. Normalization of WBC was achieved in all but the former 4 patients after a median of 2.3 cycles. All patients had died by the time of analysis, 16 due to progression, one due to pneumonia and one due to cerebral haemorrhage. Median overall survival was 15.85 months. The median survival of the comparator non-proliferative group was 11.58 months. This was not significantly different from that of the proliferative group (15.85 vs 11.58 months, respectively; log rank test: p=0.25). These results support the use of azacitidine in patients with proliferative disease, increasing treatment options in these patients.
200 CLINICAL OUTCOMES OF AML PATIENTS TREATED WITH AZACITIDINE IN PORTUGAL: A RETROSPECTIVE MULTICENTER STUDY A.M. Almeida1, A.R. Ferreira2, M.J. Costa2, I. Conde2, I. Bogalho1, K. Alnajjar1, M. Alpoim3, S. Esteves1, G. Brás3, E. Cortesão4, R. Pinto3 1 Haematology, Instituto Português de Oncologia Francisco Gentil Lisboa, Lisbon, Portugal; 2Haematology, Centro Hospitalar Lisboa Norte - Hospital Santa Maria, Lisbon, Portugal; 3Haematology, Hospital São João, Porto, Portugal; 4Haematology, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal Acute myeloid leukemia (AML) in elderly patients has a poor prognosis when treated with intensive chemotherapy (IC). There is, therefore, a need for new treatment options. Despite the blast cut-off of 20% which defines AML, elderly patients often display more indolent disease behaviour, resembling that seen in high risk myelodysplastic syndromes (MDS). Several studies have demonstrated the efficacy of Azacitidine, approved for use in MDS, in patients with AML unfit for IC. We present a multi-centre retrospective analysis of efficacy of azacitidine in 123 AML patients unfit for IC or relapsed/refractory to IC. Median age at diagnosis was 69 years; 67% were men. At diagnosis, 75% of patients were anemic, 38% neutropenic and 46% thrombocytopenic. Secondary AML was diagnosed in 45% of patients. Karyotypes were normal in 40%, intermediate risk in 23% and poor risk in 21%. Patients started azacitidine a median of 1.5 months following diagnosis. It was first line therapy in 57% and second line following IC in 28%. Patients were treated until progression, toxicity or bone marrow transplant and received a median number of 5 cycles. Overall response rate was 27.6%, with 19.5% complete and 8.1% partial responders. Stable disease at time of assessment was seen in 17.9% and progression in 17.1%. Haematological improvement was achieved in 44.7% of patients. Of the whole population, 4 (3.3%) were not evaluable for survival. During the study period 86 deaths were reported. The main cause of death was disease progression (64%). The other main identified
cause was infectious (12%). Median overall survival was 15.7 months. Response to 5-AZA had a significant impact in overall survival. The median survival observed in patients achieving CR or PR was 19.2 months, in patients with SD was 24.6 months and in patients with PD was 6.4 months (p=0.006). Pairwise comparisons show a significant difference in overall survival between PD and CR+PR and between PD and but not between CR+PR and SD. The median survival was significantly higher in patients with haematological improvement (17 vs 13 months, respectively; log rank test: p=0.048). These results support the efficacy of azacitidine in AML in a similar fashion to that demonstrated in high risk MDS, increasing treatment options in these patients. 201 IRON CHELATION IN TRANSFUSION DEPENDENT MDS PATIENTS – A SINGLE CENTRE EXPERIENCE S. Rodrigues1, A. Almeida2 1 Blood transfusion, Instituto Português de Oncologia Francisco Gentil - Lisboa, Lisbon, Portugal; 2Haematology, Instituto Português de Oncologia Francisco Gentil - Lisboa, Lisbon, Portugal Iron overload is one of the major complications of transfusion dependence in MDS. Once transferrin is saturated, labile plasma iron (LPI) appears and generates free radicals which damage tissues and lead to increased morbidity and mortality. Iron chelation has been shown to reduce complications and improve survival of patients with transfusion dependent anemias. We report the outcomes of 21 patients chelated with deferasirox in our Institute since 2008. 57% were women. Fifteen had low risk myelodysplasia (MDS), 5 had aplastic anemia (AA) and 1 sicklethalassemia. Median ages were 73, 49 and 62 years respectively. MDS patients started chelation after a median transfusion burden of 71 pRBC, AA after a median of 43 pRCB and the patient with haemoglobinopathy after a 62 pRBC. Median ferritin and transferrin saturations at the start of chelation were 4769ng/ml and 88% in MDS patients, 3002ng/ml and 89% in AA patients and 5749ng/ml and 98% in the haemoglobinopathy patient. Adverse events were recorded in 12 patients: 4 reported diarrhea and nephrotoxicity was detected in 6 patients. These side effects were controlled by dose reduction in 4 patients. Two patients suspended deferasirox due to nephrotoxicity. Ten deaths were recorded. Median survival of the cohort was 4.5 years. At present, 6 patients maintain chelation, 1 with transfusion independence and 2 with reduction in transfusion requirements. Significant reduction in ferritin values was obtained in all patients. Better control was obtained in those who started chelation at lower iron overload threshold. The reduction in transfusion requirements has led to significant reduction of costs. The cost of treatment of patient who became transfusion independent reduced from 2063€/month to 319€/ month. The two patients who achieved a reduction in transfusion requirements had their treatment costs reduced from 4759€/ month to 2987€/month. The cost calculation includes cost of blood products, day hospital admission and drugs. Close monitoring of toxicities and dose adjustments permits better therapeutic success, protecting patients from organ damage a permitting a limited number to achieve haematological improvement.
202 BOTH AGE AND COMORBIDITIES NEGATIVELY IMPACT ON CLINICAL OUTCOME OF PATIENTS WITH MYELODYSPLASTIC SYNDROMES: RESULTS FROM A REAL-LIFE REGIONAL SURVEY L. Del Corso1, C. Salvetti1, R. Filiberti1, M. Clavio1, R. Lemoli1, A.M. Carella1, G.L. Forni2, M. Scudeletti3, R. Tassara4, G. Berisso5,
Poster Presentations – 13th International Symposium on Myelodyspastic Syndromes / Leukemia Research 39 S1 (2015) S1–S166
marrow blast percentage was >10% in 72% of patients; median 19% (range 1.2-98) Karyotypes were normal in 44%, intermediate risk in 27% and poor risk in 29%. Azacitidine was used as single agent as first line therapy with no prior cytoreduction in all patients. Patients started treatment a median of 2.3 months following diagnosis. Marrow response was assessed after the 6th cycle. Treatment was continued until progression in all cases. A median number of 8 cycles were administered. Marrow assessments were available in 16 patients. Responses were documented in 6 patients, of which 1 was complete and 5 were partial. Stable disease at time of assessment was seen in 4 patients and progression in 6. Transfusion independence was achieved in 8 of 10 patients who were previously transfusion-dependent. Four patients only received 1 cycle of treatment due to progression in 3 and pneumonia in one. Normalization of WBC was achieved in all but the former 4 patients after a median of 2.3 cycles. All patients had died by the time of analysis, 16 due to progression, one due to pneumonia and one due to cerebral haemorrhage. Median overall survival was 15.85 months. The median survival of the comparator non-proliferative group was 11.58 months. This was not significantly different from that of the proliferative group (15.85 vs 11.58 months, respectively; log rank test: p=0.25). These results support the use of azacitidine in patients with proliferative disease, increasing treatment options in these patients.
200 CLINICAL OUTCOMES OF AML PATIENTS TREATED WITH AZACITIDINE IN PORTUGAL: A RETROSPECTIVE MULTICENTER STUDY A.M. Almeida1, A.R. Ferreira2, M.J. Costa2, I. Conde2, I. Bogalho1, K. Alnajjar1, M. Alpoim3, S. Esteves1, G. Brás3, E. Cortesão4, R. Pinto3 1 Haematology, Instituto Português de Oncologia Francisco Gentil Lisboa, Lisbon, Portugal; 2Haematology, Centro Hospitalar Lisboa Norte - Hospital Santa Maria, Lisbon, Portugal; 3Haematology, Hospital São João, Porto, Portugal; 4Haematology, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal Acute myeloid leukemia (AML) in elderly patients has a poor prognosis when treated with intensive chemotherapy (IC). There is, therefore, a need for new treatment options. Despite the blast cut-off of 20% which defines AML, elderly patients often display more indolent disease behaviour, resembling that seen in high risk myelodysplastic syndromes (MDS). Several studies have demonstrated the efficacy of Azacitidine, approved for use in MDS, in patients with AML unfit for IC. We present a multi-centre retrospective analysis of efficacy of azacitidine in 123 AML patients unfit for IC or relapsed/refractory to IC. Median age at diagnosis was 69 years; 67% were men. At diagnosis, 75% of patients were anemic, 38% neutropenic and 46% thrombocytopenic. Secondary AML was diagnosed in 45% of patients. Karyotypes were normal in 40%, intermediate risk in 23% and poor risk in 21%. Patients started azacitidine a median of 1.5 months following diagnosis. It was first line therapy in 57% and second line following IC in 28%. Patients were treated until progression, toxicity or bone marrow transplant and received a median number of 5 cycles. Overall response rate was 27.6%, with 19.5% complete and 8.1% partial responders. Stable disease at time of assessment was seen in 17.9% and progression in 17.1%. Haematological improvement was achieved in 44.7% of patients. Of the whole population, 4 (3.3%) were not evaluable for survival. During the study period 86 deaths were reported. The main cause of death was disease progression (64%). The other main identified
cause was infectious (12%). Median overall survival was 15.7 months. Response to 5-AZA had a significant impact in overall survival. The median survival observed in patients achieving CR or PR was 19.2 months, in patients with SD was 24.6 months and in patients with PD was 6.4 months (p=0.006). Pairwise comparisons show a significant difference in overall survival between PD and CR+PR and between PD and but not between CR+PR and SD. The median survival was significantly higher in patients with haematological improvement (17 vs 13 months, respectively; log rank test: p=0.048). These results support the efficacy of azacitidine in AML in a similar fashion to that demonstrated in high risk MDS, increasing treatment options in these patients. 201 IRON CHELATION IN TRANSFUSION DEPENDENT MDS PATIENTS – A SINGLE CENTRE EXPERIENCE S. Rodrigues1, A. Almeida2 1 Blood transfusion, Instituto Português de Oncologia Francisco Gentil - Lisboa, Lisbon, Portugal; 2Haematology, Instituto Português de Oncologia Francisco Gentil - Lisboa, Lisbon, Portugal Iron overload is one of the major complications of transfusion dependence in MDS. Once transferrin is saturated, labile plasma iron (LPI) appears and generates free radicals which damage tissues and lead to increased morbidity and mortality. Iron chelation has been shown to reduce complications and improve survival of patients with transfusion dependent anemias. We report the outcomes of 21 patients chelated with deferasirox in our Institute since 2008. 57% were women. Fifteen had low risk myelodysplasia (MDS), 5 had aplastic anemia (AA) and 1 sicklethalassemia. Median ages were 73, 49 and 62 years respectively. MDS patients started chelation after a median transfusion burden of 71 pRBC, AA after a median of 43 pRCB and the patient with haemoglobinopathy after a 62 pRBC. Median ferritin and transferrin saturations at the start of chelation were 4769ng/ml and 88% in MDS patients, 3002ng/ml and 89% in AA patients and 5749ng/ml and 98% in the haemoglobinopathy patient. Adverse events were recorded in 12 patients: 4 reported diarrhea and nephrotoxicity was detected in 6 patients. These side effects were controlled by dose reduction in 4 patients. Two patients suspended deferasirox due to nephrotoxicity. Ten deaths were recorded. Median survival of the cohort was 4.5 years. At present, 6 patients maintain chelation, 1 with transfusion independence and 2 with reduction in transfusion requirements. Significant reduction in ferritin values was obtained in all patients. Better control was obtained in those who started chelation at lower iron overload threshold. The reduction in transfusion requirements has led to significant reduction of costs. The cost of treatment of patient who became transfusion independent reduced from 2063€/month to 319€/ month. The two patients who achieved a reduction in transfusion requirements had their treatment costs reduced from 4759€/ month to 2987€/month. The cost calculation includes cost of blood products, day hospital admission and drugs. Close monitoring of toxicities and dose adjustments permits better therapeutic success, protecting patients from organ damage a permitting a limited number to achieve haematological improvement.
202 BOTH AGE AND COMORBIDITIES NEGATIVELY IMPACT ON CLINICAL OUTCOME OF PATIENTS WITH MYELODYSPLASTIC SYNDROMES: RESULTS FROM A REAL-LIFE REGIONAL SURVEY L. Del Corso1, C. Salvetti1, R. Filiberti1, M. Clavio1, R. Lemoli1, A.M. Carella1, G.L. Forni2, M. Scudeletti3, R. Tassara4, G. Berisso5,