Relationship Between Chelation and Clinical Outcomes in Lower-Risk Patients with Myelodysplastic Syndrome (MDS): Registry Analysis at 5 Years
Authors: Lyons Roger M. , Marek Billie J. , Paley Carole , Esposito Jason , McNamara Katie , Garbo Lawrence , DiBella Nicholas , Garcia-Manero Guillermo 
Published: October 2019

Abstract

Introduction: We prospectively collected data from lower-risk patients (pts) with MDS in an ongoing US registry in order to assess the association between chelation and clinical outcomes. In addition, we evaluated the association between chelation and overall survival (OS). Here we report outcomes at 5 years.
Methods: The registry enrolled 600 pts from 107 US centers. Pts were ≥18 years old with lower-risk MDS (WHO, FAB, and/or IPSS criteria) and transfusional iron overload (serum ferritin ≥1000 µg/L and/or ≥20 packed red blood cell units and/or ≥6 units every 12 weeks). Pts were analyzed by iron chelation status; ie, had never been chelated or had ever used iron chelation, and a subgroup of the latter grouppts with ≥6 mo of chelation. Pts were evaluated every 6 mo for 5 years or until death with respect to characteristics, survival, disease status, comorbidities, cause of death, and MDS therapy.
Results: 600 pts (median age, 76 years [range, 21-99], 346 [57.8%] male, 519 [86.6%] Caucasian) were evaluated. IPSS status was similar across chelation groups. Chelated pts (n=271) had a greater median number of lifetime units transfused at the time of enrollment vs nonchelated pts (n=328): 38.5 vs 20.0. At baseline, cardiac and vascular comorbidities (CVC) were significantly higher in nonchelated vs chelated pts (52.4% vs 34.3% [P<0.0001], 59.8% vs 48.0% [P=0.0039], respectively). Endocrine comorbidities (EC) were numerically higher in nonchelated vs ≥6 mo chelated pts (44.2% vs 35.6%). As of May 1, 2014, 61 pts continue in the registry; 538 discontinued (400 died, 66 lost to follow-up, 46 completed study, and 26 discontinued for other reasons). Of the 271 chelated pts, 187 (69.0%) were chelated with deferasirox, 40 (14.8%) with deferasirox and deferoxamine, 32 (11.8%) with deferoxamine, and 1 (0.4%) with an unknown chelator; in 11 (4.1%), the chelator name was not provided. Cumulative duration of chelation was 18.9 mo in pts who had ever used iron chelation and 27.0 mo in pts with ≥6 mo of iron chelation.
OS from diagnosis of MDS and time to acute myeloid leukemia (AML) were significantly greater in the chelated vs nonchelated pts (P<0.0001 for both). In pts with CVC, median OS was also significantly greater in chelated vs nonchelated pts (67.66 vs 43.40 mo; P<0.0001). In pts with EC, median OS was also greater in chelated pts (74.98 vs 44.63 mo; P<0.0001) (Table).
Patients with ≥6 mo of chelation had numerically fewer deaths in the registry, numerically greater OS, time to death, and time to AML transformation vs pts who had any chelation (Table).
Conclusions: Limitations of these analyses include variation in time from diagnosis, duration of chelation, impact of pt clinical status on decision to chelate, and optional conduct of clinical assessments. Nonetheless, the results after 5 years of follow-up of lower-risk pts with MDS suggest iron chelation therapy is associated with improved OS and longer time to AML transformation. Causation has not been established.
Abstract 1350. TABLE. Characteristics of Patients Nonchelated, Chelated, and Chelated ≥6 Months Nonchelated n=328 Chelated n=271 Chelated ≥6 Months n=202 Time to death, median (min/max) mo 47.8 (43.4, 53.1) 88.0 (78.4, 103.0) *P<0.0001 100.0 (83.4, 118.2) *P<0.0001 Deaths (n), % 239 (72.9) 161 (59.4) *P=0.0005 115 (56.9) *P=0.0002 Median OS (mo): No CVCMedian OS (mo): With CVC 34.0 (n=42) 43.4 (n=286) 69.3 (n=72) 67.7 (n=199) *P<0.0001 79.3 (n=60) 72.6 (n=142) *P<0.0001 Median OS (mo): No ECMedian OS (mo): With EC 38.5 (n=162) 44.6 (n=166) 67.1 (n=149) 75.0 (n=122) *P<0.0001 69.6 (n=114) 81.8 (n=88) *P<0.0001 Time to AML transformation from diagnosis, median (min, max) mo 46.4 (6.9, 82.5) 72.1 (16.4, 176.6) *P<0.0001 78.8 (16.4, 176.6) *P<0.0001 AML transformation, n (%) 34 (10.4) 17 (6.3) 14 (6.9) Cause of death, n (%) MDS/AML 103 (31.4) 73 (26.9) 53 (26.2) Cardiac 36 (11.0) 21 (7.7) 15 (7.4) Infection 27 (8.2) 14 (5.2) 14 (6.9) Other 16 (4.9) 16 (5.9) 10 (5.0) Unknown 29 (8.8) 18 (6.6) 12 (5.9) Malignancy 14 (4.3) 2 (0.7) 0 (0.0) Respiratory 7 (2.1) 7 (2.6) 4 (2.0) Multiorgan failure 3 (0.9) 3 (1.1) 3 (1.5) CVA 1 (0.3) 5 (1.8) 3 (1.5) GvHD/transplant 3 (0.9) 2 (0.7) 1 (0.5) CVC, cardiovascular comorbidity; EC, endocrine comorbidity; CVA, cerebrovascular accident; GvHD, graft-vs-host disease *Versus nonchelated.

Disclosures
Paley: Novartis Pharma: Employment. Esposito:Novartis Pharma: Employment. McNamara:Novartis Pharmaceuticals Corporation: Employment. Garcia-Manero:Novartis Pharma: Research Funding.