24-Month Analysis of the Impact of Chelation on Clinical Outcomes in a 600 Patient Registry of Lower-Risk MDS Patients

Abstract

Abstract 2800 Introduction:Many patients with MDS require regular transfusions. Several reviews have documented poorer clinical outcomes and overall survival (OS) in transfusion-dependent MDS patients. A US registry of 600 lower-risk MDS patients prospectively collected data on clinical outcomes in chelated and non-chelated transfused patients. This 24-month interim analysis reports on cardiac events, leukemic transformation and OS. Methods:This is a 5-year, non-interventional registry in MDS patients (aged ≥18 years) with lower-risk MDS (based on WHO, FAB and/or IPSS criteria) from 107 US centers. Patients had to have transfusional iron overload (serum ferritin ≥1000 μg/L and/or ≥20 packed red blood cell units and/or ongoing transfusion requirement of ≥6 units every 12 weeks). Follow-up was every 6 months for up to 60 months or death. Use of chelation therapy was not required. Chelated patients were those who had ever used iron chelation; a sub-analysis was done on patients with ≥6 months chelation. Assessments included demographics, disease status, MDS therapy, comorbidities, and causes of death. Differences between non-chelated and chelated patients are reported. Results:600 patients enrolled; as of May 26, 2011, 249 continued in the registry. 351 patients discontinued due to: lost to follow-up (n=51, 8.5%); death (n=278, 46.3%); other (n=22, 3.7%). 263/600 patients received chelation therapy, of whom 191 received ≥6 months.Table 1Demographics, IPSS risk status and transfusion burdenNon-chelated n(%)*Chelated n(%)*Chelated ≥6 months n(%)*Age, yrs Median (range)77 (47–99)75 (21–94)74 (21–94)Male:Female ratio1.42:11.31:11.20:1IPSS risk status–low56 (33.7)56 (44.1)38 (40.0)IPSS risk status - INT-1110 (66.3)71 (55.9)57 (60.0)Baseline ferritin, ng/mL Median (range)1353 (3–7379)1512 (81–16422)1500 (81–16422)Median number of Lifetime units transfused20.039.044.0Units transfused/4 weeks while on registry1.512.112.19*n (%) unless otherwise indicatedLeukemic transformation and cardiac events were more common in non-chelated patients (Table 2). Time to leukemic transformation was significantly shorter in non-chelated versus chelated patients. A greater percentage of deaths occurred in non-chelated patients; time to death was significantly shorter in non-chelated versus chelated patients. The most frequent reasons for death were MDS/AML, cardiac, and infection.Table 2Summary of AML transformation, cardiac events and deathsPatient categoriesNon-chelated n (%)ChelatedAll n (%)≥6 months n (%)AML transformation30 (8.9)12 (4.6)10 (5.2)Mean±SD time to transformation (mos)27.3±20.340.6±25.340.8±27.0Cardiac events155 (46.0)113 (43.0)76 (39.8)DeathsNumber (%)171 (50.7)107 (40.7)70 (36.6)Median (25th, 75th percentiles) time to death (mos)*52.2† (24.0, 136.2)99.3†‡ (54.1, NA)104.4‡ (63.4, NA)Causes of DeathMDS/AML75 (22.3)47 (17.9)32 (16.8)Cardiac28 (8.3)15 (5.7)10 (5.2)Infection22 (6.5)8 (3.0)8 (4.2)Unknown16 (4.7)10 (3.8)6 (3.1)Other10 (3.0)9 (3.4)4 (2.1)Malignancy9 (2.7)3 (1.1)0Respiratory7 (2.1)7 (2.7)4 (2.1)Multiorgan failure2 (0.6)2 (0.8)2 (1.0)CVA1 (0.3)4 (1.5)3 (1.6)GvHD/transplant1 (0.3)2 (0.8)1 (0.5)NA, not attained; CVA, cerebrovascular accident; GvHD, graft versus host disease.*Time to death from diagnosis.†P<0.0001, non-chelated vs chelated‡P<0.0001, non-chelated vs chelated≥6 months.At baseline, non-chelated patients had a higher incidence of cardiac disorders than chelated patients (51.3% vs 35%). While on the registry, non-chelated patients had a higher incidence of comorbidities than did chelated patients, predominantly vascular, cardiac and endocrine. Lifetime use of MDS therapies (pre- and on-registry) was lower among non-chelated versus chelated patients (88.4% vs 94.3%). Conclusions:At the 24-month analysis, use of chelation was associated with lower AML transformation, fewer cardiac events, and better OS. The two patients groups had similar age, gender, and risk status breakdown (IPSS); however the non-chelated group had a higher prevalence of cardiac comorbidities. Ongoing follow-up for the 5-year duration of this registry will provide further data on differences in outcomes between chelated and non-chelated patients. Disclosures:Lyons:Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Telik: Research Funding; Alexion: Consultancy, Honoraria; Novartis: Research Funding. Sharma:Novartis: Employment. Paley:Novartis: Employment. Esposito:Novartis: Employment.