ANEMIA IN CANCER ROLE OF IV IRON IRON DEFICIENCY Absolute vs - - PowerPoint PPT Presentation
ANEMIA IN CANCER ROLE OF IV IRON IRON DEFICIENCY Absolute vs functional Absolute iron deficiency anemia = no iron stores : ferritin < 20 g/L in N individual < 100 g/L in infl/cancer patient Functional iron deficiency =
µ anemia
= no iron stores : ferritin < 20 µg/L in N individual < 100 µg/L in infl/cancer patient
= iron stores present but ID in erythroid bone marrow a) Iron sequestration in macrophages µ / N anemia
b) Increased iron requirements N anemia
Absolute ID
Empty iron stores
FID FID
Functional ID (Inflammation/cancer)
Blocked iron release
FID FID
Functional ID (EPO therapy)
Iron need exceeds delivery
Macrophages Red blood cells Plasma transferrin Marrow
TSat < 20% %HYPO > 5% CHr < 28 pg
Henry et al, Oncologist 12:231, 2007
Epo 40,000 U/wk No iron Oral iron IV iron dextran
Bastit et al, JCO 26:1611, 2008 Auerbach et al, JCO 22:1301, 2004
Epo 40,000 U/wk No iron Oral iron IV iron gluconate DA 500 µg q3w No/oral iron IV iron sucrose Response = Hb +2 g/dL or Hb 12 gr/dL Non-myeloid malignancies on chemotherapy
Gafter-Gvili et al, Blood (Suppl 1), 2010
Hematopoietic response 30% higher
Petrelli et al, J.Cancer Res.Clin.Oncol., 2011
Beguin et al, AJH 88:990, 2013 Bastit et al, JCO 26:1611, 2008
Lymphoid malignancies AutoHCT DA 300 µg q2w No iron IV iron sucrose Non myeloid malignancies Chemo DA 500 µg q3w No iron IV iron sucrose
10 20 30 40 50 Group 2 Group 3 Yes No
P=0.0276 P=0.005
Gafter-Gvili et al, Blood (Suppl 1), 2010
Transfusions 23% fewer
Petrelli et al, J.Cancer Res.Clin.Oncol., 2011
Beguin et al, AJH 88:990, 2013
Lymphoid malignancies AutoHCT DA 300 µg q2w No iron IV iron sucrose Lymphoid malignancies No chemo Epo 30,000 U/wk No/oral iron IV iron sucrose
Hedenus et al, Leukemia 21:627, 2007
Max = 7 doses
Group 2 Group 3 500 1000 1500 2000 2500
P=0.015
Total dose of Darbepoetin (µg)
Beguin et al, AJH 88:990, 2013
Drug acquisition costs
Epo without iron 3,346 € Epo with iron 2,811 € + 91 € (iron) Cost savings = 444 €
Overall cost saving of 11% by adding IV iron to EPO
Hedenus et al, Leukemia 21:627, 2007 Hedenus et al, J.Clin.Pharm.Ther. 33:365, 2008
Total costs
with 16 wks of epoetin beta + IV iron
Drug cost saving of 13% by adding IV iron to EPO
Steinmetz et al, Ann.Oncol. 24:475, 2013
74.3% 11.2% 5.7% 2.4% 1.9% 8.1% 17.1%
Anti-tumour treatment
Chemotherapy Monoclonal antibody Hormone therapy Radiotherapy Tyrosine kinase inhibitor Other No current therapy
median 1000 mg iron / patient (interquartile range 600-1500 mg)
*More than one treatment per patient possible
Steinmetz et al, Ann.Oncol. 24:475, 2013
*More than one treatment per patient possible
* Transfused patients censored from analysis prior transfusion
8 9 10 11 12 13 14
median Hb (g/dL)
All, censored* FCM + ESA* FCM only (no ESA)*
Efficacy population N=420
Steinmetz et al, Ann.Oncol. 24:475, 2013
*More than one treatment per patient possible
Efficacy population N=420
Ferritin ≥500 ng/mL associated with slow Hb increase
Hedenus et al, Med.Oncol. 2014;31:302
in BM or ferritin >30 ng/mL [women] to >40 ng/mL [men])
(transfusion, ESA, iron).
Hedenus et al, Med.Oncol. 2014;31:302
Hedenus et al, Med.Oncol. 2014;31:302
Hedenus et al, Med.Oncol. 2014;31:302
Indication
Objectives
Response : 2/3
Plasma Macrophages Marrow Venofer 300 mg IV in 1 H qow x 3 Injectafer / Ferrinject 1000 mg IV in 30 min Faster response Higher response rate Fewer transfusions Less EPO used
Steinmetz et al, Ann.Oncol. 24:475, 2013
IDA ACD
ID in cancer Absolute ID (no iron stores) Ferritin < 100 ng/mL Functional ID (iron stores +/++) Ferritin ≥ 100 ng/mL Anemia TSAT <20%
IV iron ESA ± IV iron
Assess iron status at initial diagnosis and monthly during any kind of anti-anemia therapy