ANEMIA IN CANCER ROLE OF IV IRON

Transcription

1 ANEMIA IN CANCER ROLE OF IV IRON

2 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

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

4 ANEMIA IN CANCER ESA + IV IRON

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

6 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

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

8 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

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

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

11 ANEMIA IN CANCER IV IRON ALONE

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

13 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 mg) Anti-tumour treatment 1.9% 2.4% 5.7% 8.1% 17.1% 74.3% Chemotherapy Monoclonal antibody Hormone therapy Radiotherapy Tyrosine kinase inhibitor Other No current therapy 11.2% *More than one treatment per patient possible Steinmetz et al, Ann.Oncol. 24:475, 2013

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

15 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

16 ANEMIA THERAPY IN CANCER IV iron alone : Ferinject 1. Indolent lymphoid malignancy 2. Anemia (Hb 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

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

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

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

20 CONCLUSIONS

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

22 EPO THERAPY IN CANCER IV iron 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 Macrophages Plasma Marrow

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

24 THANK YOU!