Evaluation of ECOG Performance Status at Diagnosis and Relapse in Patients with Acute Myeloid Leukemia

Abstract

Background: Eastern Cooperative Oncology Group (ECOG) performance status (PS) is often utilized in treatment decision-making for patients with acute myeloid leukemia (AML). Patients with relapsed or refractory (R/R) disease have a particularly poor prognosis and require complex treatment decisions that utilize patient preference, genetic profile and PS. Currently, limited data exist on the trend of PS between initial diagnosis and R/R AML, and we aimed to characterize PS in R/R AML and its association with short and long term survival. Methods: We utilized an institutional database from the University of Washington/ Fred Hutchinson Cancer Center to retrospectively identify a subset of patients with AML or other high-grade myeloid neoplasms (≥10% blasts in blood or marrow at diagnosis) who received both induction and salvage chemotherapy for first relapse between January 1, 2008 and December 1, 2021. Salvage treatment was divided into high intensity (cytarabine greater than 1g/m 2/dose), intermediate intensity (7+3 or similar), reduced intensity (i.e., hypomethylating agents) or other (investigational agents not fitting into prior categories or supportive care alone). The McNemar test was used for matched-pair analysis of PS at two timepoints. The Kaplan-Meier method was used for analysis of overall survival (OS). Multivariable regression was used to evaluate associations with 4 week survival. Multivariable Cox regression was used for analysis of overall survival. All statistical analyses were performed using R 4.2.1 (2022). Results: We identified 160 patients with R/R disease. Patients with missing PS data (n=33) or otherwise not meeting inclusion criteria (n=20) were excluded (baseline characteristics of 107 patients in Table 1). No significant change was identified in PS at initial diagnosis versus R/R (PS≤1 71% vs 63%, p=0.19). More patients had the same PS at R/R disease (51.4%) as compared to initial diagnosis, though some had worse PS (27.1%), and others had better PS (25.2%). At initial diagnosis, patients with poor PS had similar induction chemotherapy intensity to those with good PS (PS≤1 treatment intensity: high: 42.1%, intermediate: 34.2%, reduced: 23.7%, other: 0%; PS≥2 treatment intensity: high: 38.7%, intermediate: 32.2%, reduced: 25.8%, other: 3.2% (p=0.55). At R/R disease, patients with poor PS were more likely to receive less intensive therapy (PS≤1 treatment intensity: high: 52.2%, intermediate:14.9%, reduced: 14.9%, other: 17.9%; PS≥2 treatment intensity: high: 27.5%, intermediate:7.5%, reduced:32.5%, other: 32.5% (p=0.001)). There was no correlation between PS at R/R disease and rate of complete remission without measurable residual disease (PS≤1 = 26.8%, PS≥2 =20%, p=0.49) or treatment failure (PS≤1 = 38.8%, PS≥2 =35%, p=0.84). The 4-week unadjusted mortality rate at R/R was 10.4% for patients with PS≤1, and 25.6% for patients with PS ≥2 (p=0.04). OS was longer in patients with good PS (PS≤1) at R/R disease (8.9 months vs 3.0 months). In multivariate analysis, poor ECOG (HR 2.13, 95% CI 1.09-4.17) was correlated with worse OS, while favorable ELN score (HR 0.43, 95% CI 0.19-0.99) and transplant (HR 0.29, 95% CI 0.17-0.49) were associated with improved OS. We did not find a significant association between age, gender, secondary status, or change in PS and OS in our preliminary analysis. Conclusions: We did not identify a significant change in PS in R/R disease. Our preliminary results suggest that poor PS at R/R was correlated with an increased 4-week mortality rate and worse OS. Interestingly, we did not find a significant difference in treatment intensity for patients with poor PS at initial presentation. In addition, at R/R disease, patients with good and poor PS had similar rates of treatment failure despite patients with good PS being treated with more intensive regimens. A limitation of our work is possible selection bias, as patients with significant functional decline may not have returned for evaluation at R/R disease. Further work is needed to identify if there is a meaningful association between change in PS and outcomes at R/R disease.