Anemia of Cancer

Background

• Anemia is common in patients with cancer, with a prevalence of 30%-90%, depending on the definition of anemia, cancer type, and stage.
• Causes include reduced red cell production (for example, from reduced erythropoietin [EPO] production due to kidney disease, inflammation leading to functional iron deficiency, bone marrow infiltration, chemotherapy, and pure red cell aplasia), increased red cell destruction (for example, from red autoimmune hemolytic anemia, erythrophagocytosis, and cancer-associated thrombotic microangiopathy), and sequestration (from hypersplenism), and blood loss.
• Patients may be asymptomatic or may present with symptoms of anemia including dizziness, syncope, palpitations, shortness of breath on exertion, headache, chest pain, depression, and impaired cognitive ability.

Evaluation

• Evaluate patients with cancer who have hemoglobin (Hb) < 11 g/dL (110 g/L) or a drop in Hb of ≥ 2 g/dL (20 g/L) from baseline (Strong recommendation).
• Perform a complete blood count, peripheral blood smear, and reticulocyte count (Strong recommendation).
• Perform additional testing, as indicated, to identify an underlying cause of anemia such as (Strong recommendation):
  • hemolysis, which includes direct and indirect antiglobulin test, disseminated intravascular coagulation panel, serum haptoglobin, indirect bilirubin, and lactate dehydrogenase
  • iron indices, which includes serum iron, total iron binding capacity/transferrin saturation, and ferritin
  • nutritional status including serum vitamin B12 and folate
  • renal function, which includes serum blood urea nitrogen and creatinine

Management

• Management according to the cause of anemia:
  • If the cause of anemia is identified during evaluation, treat the underlying cause as indicated (Strong recommendation).
  • If the likely cause of anemia is cancer-related inflammation and/or myelosuppressive chemotherapy treatment may involve:
    • red blood cell transfusion in symptomatic patients (for example, sustained tachycardia) and patients at high risk (with declining Hb due to recent chemotherapy or radiation) or those who are asymptomatic but with comorbidities (for example, cardiac disease)
    • erythropoiesis-stimulating agent (ESA) in patients receiving myelosuppressive chemotherapy without other identifiable cause of anemia or those receiving palliative therapy (noncurative), after weighing risks and benefits of ESA compared to red blood cell transfusion
    • IV iron in patients with evidence of functional iron deficiency taking ESA
• Management according to treatment modality:
  • Red blood cell (RBC) transfusion
    • consider a RBC transfusion for patients with cancer- and chemotherapy-induced anemia who are at high risk (for example, progressive decline in Hb with recent intensive chemotherapy or radiation) or asymptomatic with cardiac disease, chronic pulmonary disease, or cerebrovascular disease (Weak recommendation)
    • give a RBC transfusion to symptomatic patients with sustained tachycardia, tachypnea, chest pain, dyspnea on exertion, light-headedness, syncope, or severe fatigue (Strong recommendation)
  • Erythropoiesis-stimulating agent (ESA):
    • While ESAs have been reported to increase Hb and reduce transfusion requirements in many patients with chemotherapy-associated anemia, they are associated with increased risk of thromboembolism, tumor progression, and mortality.
    • Consider in patients (Weak recommendation):
      • with Hb < 10 g/dL (100 g/L) receiving myelosuppressive therapy for noncurative intent without other identifiable causes of anemia, depending on patient preferences
      • undergoing palliative treatment, depending on patient preferences
      • who refuse blood transfusions
    • Contraindications include patients (Weak recommendation):
      • with cancer not receiving therapy (an exception is patients with low-risk myelodysplastic syndrome)
      • receiving nonmyelosuppressive therapy
      • receiving myelosuppressive chemotherapy with curative intent
    • The target Hb is uncertain, but consider using the lowest possible dose needed to avoid transfusions.
    • Epoetin, darbepoetin, and epoetin biosimilars are considered comparable in an efficacy and safety profile.
    • Typical ESA dosing and dose modifications include:

Table 1. Package Insert Dosing Schedule for ESAs and FDA Recommendations for Dose Modifications

• Alternative ESA dosing regimens may also be considered.
• Discontinue ESA therapy if after 8 weeks of therapy, there is no response (measured by Hb levels or need for transfusion), or when chemotherapy is discontinued.
• Iron Supplementation:
  • Administer IV or oral iron therapy in patients with absolute iron deficiency (Strong recommendation). Definition of absolute iron deficiency vary by professional organizations.
  • Consider IV iron in patients with functional iron deficiency taking ESA (Weak recommendation).
  • Routine IV iron is not generally indicated in patients with possible functional iron deficiency who are not taking an ESA. If IV iron is given, the goal should be avoidance of red blood cell transfusions.