A Risk Model for Chemotherapy-Induced Anemia (CIA) in Cancer Patients.
Authors: Lyman Gary H. , McMahon Brandon , Kuderer Nicole M. , Crawford Jeffrey , Wolff Debra , Culakova Eva , Poniewierski Marek S. , Dale David C. 
Published: April 2020

Background: Anemia represents the most common hematological toxicity in cancer patients receiving systemic chemotherapy and is associated with considerable morbidity and cost (Lyman‚ Value in Health 2005). Current ASH/ASCO guidelines call for intervention at a hemoglobin (Hgb) &lt;10 gm/dl. Treatment options include transfusion or administration of an erythropoietic-stimulating protein (ESP). A recent meta-analysis demonstrated the clinical value of early versus late intervention with an ESP (Lyman‚ Cancer‚ 2005 in press). An accurate and valid risk model for CIA is needed to select patients for ESP treatment early in the course of chemotherapy when it can be most effective.

Methods: More than 3‚000 patients with cancer of the breast‚ lung‚ colon and ovary or malignant lymphoma initiating a new chemotherapy regimen have been prospectively registered at 115 randomly selected U.S. practice sites. Data on at least one cycle of chemotherapy were available on 2‚842 patients. A logistic regression model for Hgb &lt;10 gm/dl based on pretreatment characteristics was developed and predictive test performance characteristics examined.

Results: Over a median of three cycles of chemotherapy, Hgb &lt;10 gm/dl was reported one or more times in 817 (28.7%) patients. Significant independent predictive factors for Hgb &lt;10 gm/dl include: history of peptic ulcer (OR=1.90; P=.015), myocardial infarction (OR=1.94; P=.009), or congestive heart failure (OR=2.13; P=.017), increasing age (OR=1.02; P=.002), female gender (OR=2.40; P&lt;.001), ECOG performance status (OR=1.24; P=.002), Charlson Comorbidity Index (OR=1.06, P=.002), body surface area (OR=3.75, P&lt;.001), low baseline hemoglobin (OR=1.95, P&lt;.001), pretreatment hematocrit (OR=.85, P&lt;.001), and glomerular filtration rate (OR=0.99, P=.027), and regimens containing anthracyclines (OR=3.21, P&lt;.001), cisplatinum (OR=3.86, P&lt;.001) or carboplatinum (OR=2.71, P&lt;.001). Model fit was excellent (P&lt;.001), R2=0.455 and c-statistic = 0.775 [95% CL: .76–.79, P&lt;.0001]. Individual predicted risk of Hgb &lt;10 gm/dl based on the model ranged from 0 to 98% with mean and median probabilities of 0.28 and 0.22, respectively. Based on a risk cutpoint of 20%, 1,541 patients (55%) were classified as high risk and 1,282 as low risk. The average risks of Hgb &lt;10 gm/dl during chemotherapy in high and low risk subjects were 43% and 12%, respectively. Model test performance characteristics [±95% CL] included: sensitivity: 81% [78–84]; specificity: 56% [54–58]; likelihood ratio positive: 1.85 [1.74–1.96]; likelihood ratio negative: 0.34 [0.29–0.39]; positive predictive value: 43% [40–45]; negative predictive value: 88% [86–90] and diagnostic odds ratio: 5.47 [4.50–6.66].

Conclusions: This risk model identified cancer patients initiating chemotherapy who are at risk for clinically significant anemia using common clinical parameters. Validation of the model in a separate population of patients is in progress.