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 µ anemia = no iron stores : ferritin < 20 µg/L in N individual < 100 µg/L in infl/cancer patient • Functional iron deficiency = iron stores present but ID in erythroid bone marrow a) Iron sequestration in macrophages µ / N anemia - Inflammation (ACD, anemia of chronic disease) b) Increased iron requirements N anemia - EPO therapy

EPO THERAPY IN CANCER Resistance : (Functional) iron deficiency Absolute ID Empty iron stores FID FID Functional ID (Inflammation/cancer) TSat < 20% Blocked iron release %HYPO > 5% CHr < 28 pg FID FID Functional ID (EPO therapy) Iron need exceeds delivery Red blood cells Macrophages Plasma transferrin Marrow

ANEMIA IN CANCER ESA + IV IRON

EPO THERAPY IN CANCER IV iron : more responses Non-myeloid malignancies on chemotherapy Epo 40,000 U/wk DA 500 µg q3w Epo 40,000 U/wk No iron No/oral iron No iron Oral iron IV iron sucrose Oral iron IV iron dextran IV iron gluconate Response = Hb +2 g/dL or Hb 12 gr/dL Auerbach et al, Bastit et al, Henry et al, JCO 26:1611, 2008 Oncologist 12:231, 2007 JCO 22:1301, 2004

EPO THERAPY IN CANCER Meta-analysis : IV iron vs std care Hematopoietic response 30% higher Petrelli et al, J.Cancer Res.Clin.Oncol., 2011 Gafter-Gvili et al, Blood (Suppl 1), 2010

EPO THERAPY IN CANCER IV iron : fewer transfusions Non myeloid malignancies Lymphoid malignancies Chemo AutoHCT DA 500 µg q3w DA 300 µg q2w No iron No iron IV iron sucrose IV iron sucrose P=0.005 P=0.0276 50 40 30 Yes 20 No 10 0 Group 2 Group 3 Bastit et al, JCO 26:1611, 2008 Beguin et al, AJH 88:990, 2013

EPO THERAPY IN CANCER Meta-analysis : IV iron vs std care Transfusions 23% fewer Petrelli et al, J.Cancer Res.Clin.Oncol., 2011 Gafter-Gvili et al, Blood (Suppl 1), 2010

EPO THERAPY IN CANCER IV iron : less ESA use Lymphoid malignancies Lymphoid malignancies No chemo AutoHCT Epo 30,000 U/wk DA 300 µg q2w No/oral iron No iron IV iron sucrose IV iron sucrose P=0.015 Total dose of Darbepoetin (µg) 2500 Max = 2000 7 doses 1500 1000 500 0 Group 2 Group 3 Hedenus et al, Leukemia 21:627, 2007 Beguin et al, AJH 88:990, 2013

EPO THERAPY IN CANCER IV iron : cost savings Overall cost saving of 11% Drug cost saving of 13% by adding IV iron to EPO by adding IV iron to EPO Total costs Drug acquisition costs with 16 wks of epoetin beta + IV iron Epo without iron 3,346 € Epo with iron 2,811 € + 91 € (iron) Cost savings = 444 € Hedenus et al, Leukemia 21:627, 2007 Beguin et al, AJH 88:990, 2013 Hedenus et al, J.Clin.Pharm.Ther. 33:365, 2008

ANEMIA IN CANCER IV IRON ALONE

ANEMIA THERAPY IN CANCER IV iron alone ? 1. Kim YT et al, Gynecol Oncol 2007;105:199 2. Dangsuwan P & Manchana, T. Gynecol Oncol 2010;116:522

ANEMIA THERAPY IN CANCER IV iron alone : Ferinject • 12-wk observational study in 68 practices in Germany • 619 anemic cancer patients who received at least one dose FCM • 91% with solid tumours (25% breast, 20% colorectal; 61% metastatic) • 83% received FCM without ESA median 1000 mg iron / patient (interquartile range 600-1500 mg) Anti-tumour treatment 17.1% Chemotherapy Monoclonal antibody Hormone therapy 8.1% Radiotherapy 1.9% Tyrosine kinase inhibitor 2.4% Other 5.7% No current therapy 74.3% 11.2% *More than one treatment per patient possible Steinmetz et al, Ann.Oncol. 24:475, 2013

ANEMIA THERAPY IN CANCER IV iron alone : Ferinject 14 Efficacy population N=420 13 median Hb (g/dL) 12 11 10 All, censored* FCM + ESA* 9 FCM only (no ESA)* 8 * Transfused patients censored from analysis prior transfusion *More than one treatment per patient possible Steinmetz et al, Ann.Oncol. 24:475, 2013

ANEMIA THERAPY IN CANCER IV iron alone : Ferinject Efficacy population N=420 Ferritin ≥ 500 ng/mL associated with slow Hb increase *More than one treatment per patient possible Steinmetz et al, Ann.Oncol. 24:475, 2013

ANEMIA THERAPY IN CANCER IV iron alone : Ferinject 1. Indolent lymphoid malignancy 2. Anemia (Hb 8.5-10.5 g/dL) 3. Functional iron deficiency (TSAT ≤ 20% and stainable iron in BM or ferritin >30 ng/mL [women] to >40 ng/mL [men]) 4. On chemotherapy 1. Any anemia treatment within 4 weeks before inclusion (transfusion, ESA, iron). 3. Monotherapy with immunotherapy agents 4. Anthracycline-containing chemotherapy 5. Serum ferritin >800 ng/mL Hedenus et al, Med.Oncol. 2014;31:302

ANEMIA THERAPY IN CANCER IV iron alone : Ferinject Hedenus et al, Med.Oncol. 2014;31:302

ANEMIA THERAPY IN CANCER IV iron alone : Ferinject Hedenus et al, Med.Oncol. 2014;31:302

ANEMIA THERAPY IN CANCER IV iron alone : Ferinject Hedenus et al, Med.Oncol. 2014;31:302

CONCLUSIONS

EPO THERAPY IN CANCER EORTC guidelines Indication Objectives ↓ transfusions • On chemotherapy • ↑ QOL • On radiotherapy or no anti-cancer treatment • Response : 2/3

EPO THERAPY IN CANCER IV iron Venofer Faster response Higher response rate 300 mg IV in 1 H qow x 3 Fewer transfusions Injectafer / Ferrinject Less EPO used 1000 mg IV in 30 min Macrophages Plasma Marrow

ANEMIA THERAPY IN CANCER Conclusion Assess iron status at initial diagnosis and monthly during any kind of anti-anemia therapy ID in cancer IDA ACD Absolute ID Functional ID (no iron stores) (iron stores +/++) Ferritin ≥ 100 ng/mL Ferritin < 100 ng/mL TSAT <20% IV iron ESA ± IV iron Anemia Steinmetz et al, Ann.Oncol. 24:475, 2013

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