Clinical importance and safety of ESAs for patients with Myelodysplastic Syndromes MDS

1
Clinical importance and safety of ESAs for
patients with Myelodysplastic Syndromes (MDS)

• Steven D. Gore, MD
• Associate Professor of Oncology
• Sidney Kimmel Cancer Center
• At Johns Hopkins
• Representing
• The MDS Foundation

2
Myelodysplastic Syndromes

• Heterogeneous group of clonal stem cell disorders
• Symptoms determined to a large extent by
  refractory cytopenias
• Refractory anemia most prominent
  symptom-producing cell deficit
• ESAs positively impact quality of life, survival,
  and progression to acute leukemias

3
Impact of anemia on MDS patients

• Chronic fatigue
• Decreased quality of life
• Medical risks of transfusion
• Transfusion reactions
• Iron Overload
• Transmission of infection
• Alloimmunization
• Decreased productive time due to transfusion
  requirements

4
Oncology Delivery in the US is No Longer
Configured to Accommodate Tranfusion

• In 2005, only 1 in 24 transfusions for oncology
  patients was given in the office setting 1 (17k
  vs. 417k in hospital)
• Extreme logistical challenges (chain of custody,
  staff training, transport)
• Demand on staff a typical transfusion requires
  4 hours 2
• No capacity or facilities (infusion space, staff
  time)

Lower rates of ESA use would potentially push
thousands of MDS patients back into hospitals for
transfusions
1 Analysis of 2005 Physician Supplier Procedure
Summary Master File 2 Uneo W, Beveridge, R
Kales AN. Presented at ASH 47th Annual Meeting,
2005 3 2006 Audit of Cytotoxic Chemotherapy
Delivery, Tandem Data 4 Analysis of AHRQ
Healthcare Cost and Utilization Project (HCUP)
data using Clinical Classification Software (CCS)
category 45 (Maintenance chemotherapy,
radiotherapy)
5
ESAs for treatment of MDS-associated anemia

• ESAs effective and safe in MDS
• Studied in hundreds of patients over greater than
  10 years
• No evidence of increased incidence of thrombosis
  in this population

6
Randomized Trial of EPO versus observation (ECOG)

• 105 MDS patients
• Supportive care versus EPO 150 u/kg/day increase
  to 300 u/kg/day if no response
• Erythroid response rate 35 in EPO arm versus 9
  in supportive care
• Response rate 30 in supportive care patients
  crossed over after worsening transfusion
  requirement
• Development of AML
• 3.6 of patients in supportive care
• 0 in EPO arm

Miller, KB et al. Blood 10424a, 2004
7
EPO Scandinavian Experience

• 129 MDS patients followed for at least 45 months
• EPO plus/minus G-CSF
• Hgb of 11.5 g/dL achieved in 39
• Transfusion independence in 29 of transfusion
  dependent patients
• Median duration of response 23 months
• No difference in survival compared to matched
  historical controls

Jadersten et al. Blood 2005. 106 803-11
8
ESAs may improve survival in some MDS patients

• Comparison of Nordic patients treated with EPO
  plus G-CSF to supportive care only patients from
  Pavia, IT
• 176 transfusion-dependent 187 untransfused but
  Hgb lt 10 g/dL
• In patients with low transfusion need (lt 2U
  RBC/month), survival superior in treated group
  (HR 0.57, p 0.015)

Jadersten et al. Blood 2006. 108158a
9
Further evidence of survival benefit

• Retrospective comparison of 284 patients from
  France treated with EPO /- G-CSF to 163
  supportive care patients (IPSS data base)
• Multivariate analysis
• EPO treated patients less likely to develop AML
  (HR 0.2 0.1 0.3)
• Better survival (HR 0.26 0.18 0.38)

Park et al. International MDS Symposium, 2007
10
Appropriate MDS patients can be selected for ESA
therapy

• Serum epo concentrations lt 500 u/mL
• Low transfusion requirement
• Addition of G-CSF patients for subset
• Monitor response with monthly reticulocyte counts
• May require high doses (1000 2000 u/kg/week
  epo 300 mcg/week darbo)

11
Summary

• Chronic transfusions represent a major burden to
  quality of life for MDS patients
• ESAs provide important palliation of anemia in a
  significant subset of MDS patients
• ESAs may improve survival in a subset of MDS
  patients
• Extremely well-tolerated in this patient
  population
• Extremely important to maintain access to ESAs
  for selected MDS patients