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

Anemia represents the most common hematological toxicity in cancer patients receiving systemic chemotherapy and is associated with considerable morbidity and cost. Current guidelines for chemotherapy-induced anemia call for intervention at a hemoglobin &lt;10 g/dL with treatment options including transfusion or an erythropoietic-stimulating agent (ESA). A meta-analysis of randomized controlled trials has demonstrated the clinical value of early versus late intervention with an ESA (Lyman Cancer, 2006). While anemia risk models based on pretreatment characteristics have recently been validated, recent safety concerns have limited use of the ESAs to patients with moderate or severe anemia. The gradual onset of anemia and response to ESAs over time provides a rationale for selecting patients for ESA support early in the course of chemotherapy.

Methods: 3640 patients with solid tumors or malignant lymphoma initiating a new regimen have been prospectively registered at 110 randomly selected U.S. practice sites. A logistic regression risk model for hemoglobin &lt;10 g/dL based on pretreatment characteristics and hematolgic events during cycle 1 was developed and model predictive performance characteristics estimated.

Results: Over a median of 3 cycles of chemotherapy, hemoglobin &lt;10 g/dL was reported one or more times in 1072 (29.5%) patients. Significant independent baseline characteristics associated with subsequent hemoglobin &lt;10 g/dL include: female gender, poor ECOG performance status, history of congestive heart failure, vascular disease or chronic pulmonary disease, cancer type, treatment with an anthracycline-, platinum- or etoposide-based regimen and baseline hemoglobin &lt;12 g/dL or platelet count &lt;150000/mm3. In addition, significant independent predictive hematologic changes during cycle 1 include: decrease in hemoglobin &gt;1 g/dL (OR=4.48; P&lt;.0001), decrease in platelet count &gt;100000/mm3 (OR=1.54;P&lt;.0001) or neutrophil count &lt;500/mm3 (OR=1.94; P&lt;.001) as well as hemoglobin &lt;12 g/dL (OR=2.0;P&lt;.001) at the start of cycle 2. Model R2 = 0.581 and c-statistic = 0.901 [95% CI: .89–.91, P&lt;.0001]. The predicted risk of hemoglobin &lt;10 g/dL ranged from 0 to 100% with mean and median probabilities of 0.16 and 0.30, respectively. Based on a risk cutpoint at the mean, 1290 patients (38%) were classified as high risk. The risks of hemoglobin &lt;10 g/dL in high and low risk subjects were 66% and 9%, respectively. Model test performance characteristics [± 95% CLs] included: sensitivity: 82%[80–84]; specificity: 82%[80–83]; positive predictive value: 66%[63–68]; negative predictive value: 91%[90–93] and diagnostic odds ratio: 20.4[16.8–24.6]. Of note, risk of hemoglobin &lt;11 g/dL in high and low risk subjects based on this model were 95% and 34%, respectively. Validation of the model in a separate population of patients is currently under way.

Discussion: This conditional risk model based on both pretreatment characteristics and first cycle events identified cancer patients receiving chemotherapy at substantial risk for clinically significant anemia. The use of ESAs early in the course of treatment based on individual risk assessment must consider both the potential benefit and risks and careful monitoring is essential.