The prevalence of anemia in cancer is 40% and can exceed 90% for those on treatment.1,2 Anemia impacts quality of life by contributing to fatigue which is the leading patient reported symptom, can lead to treatment delays and expose patients to unnecessary transfusion risks. Anemia is often untreated or suboptimally treated due to concerns about the safety of both ESA and IV iron.
Cancer associated anemia can be caused by nutritional deficiencies, hemolysis, blood loss, and chemotherapy or radiation induced myelosuppression. The underlying pathophysiology directly related to the malignancy includes:
This functional iron deficiency results in part from an increased expression of hepcidin with downregulation of iron absorption and impaired recycling of iron from macrophages.3-4
The anemia of cancer is very often treated with transfusions without first assessing iron status or considering the use of either IV iron or ESA. Iron deficiency can be absolute (usually related to bleeding) with low iron stores, or functional iron deficiency. Iron-restricted erythropoiesis can occur when ESA therapy stimulates erythropoiesis without adequate iron delivery from storage sites.5
The ESA are effective in increasing hemoglobin levels and decreasing transfusion requirements in chemotherapy – induced anemia but data has linked their use to inferior survival and worse cancer outcomes so are not recommended to be used in anemic cancer patients not on treatment or in whom treatment is given with the intent to cure. 6-7
The most frequently used tests to assess iron status are ferritin and TSAT percentage. When the ferritin is low absolute iron deficiency is present. Because it is an inflammatory biomarker and can be elevated in malignancy a TSAT under 20% suggests functional iron deficiency both of which can be treated with IV iron.8
Although oral iron is more convenient and less expensive if may not be tolerated due to gastrointestinal side effects, may not be absorbed in functional iron deficiency and may be incapable of rapidly repleting iron stores.
There have been multiple clinical trials that have been published using IV iron monotherapy to treat chemotherapy induced anemia (CIA).9-11 IV iron alone either improved hemoglobin levels, reduced transfusion or both. Any of the current IV iron preparations can be used with relative safety. Minor infusion reactions occur about 1 in 200 infusions with major infusion reactions 1 in 200,000.12
Several organizations have developed recommendations on iron monitoring and replacement in cancer patients.13 The National Comprehensive Cancer Network, (NCCN) recommends monotherapy with iron (preferably IV) for absolute iron deficiency (ferritin <30 ng/mL and transferrin saturation (TS) <20%) and in patients using ESAs with ferritin between 30 and 800 ng/mL and TS between 20 and 50%. IV iron can reduce the number of transfusions in patients with functional iron deficiency.
The European Society for Medical Oncology (ESMO) recommends iron profile monitoring. IV iron replacement is recommended in patients with iron deficiency to produce an increment in hemoglobin and reduce the need for transfusion.
The European Organization for Research and Treatment of Cancer (EORTC) recommends iron replacement to be restricted to patients with absolute or functional iron deficiency.
Three review articles that provide summaries to better understand the anemia of cancer and chemotherapy induced anemia are the following:
Gilreath JA and Rodgers GM. How I treat cancer- associated anemia. Blood 2020:136 (7):801-813.
Ganz T. Anemia of Inflammation. N Engl J Med 2019:381:1148-1157.
Anand S, Burkenroad A ,Glaspy J. Workup of Anemia in Cancer. Clinical Advances in Hematology & Oncology. 2020 ;18 (10)640-646
Additional information from SABM Literature Review and Recommendations: Cancer and Chemotherapy Induced Anemia