Disparity in utilization of multiagent therapy for acute promyelocytic leukemia (APL): A large National Cancer Database (NCDB) analysis.
Authors: Dhakal Prajwal , Lyden Elizabeth , Gundabolu Krishna , Zeidan Amer Methqal , Loh Kah Poh , Fisher Alfred , Bhatt Vijaya Raj 
Published: June 2021

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Background: Clinical trials have demonstrated a high rate of cure in APL with the use of multiagent therapy; however, overall survival in real world practice is significantly lower than that in the trials (Blood 2020; 136 (s 1): 13-14). We performed a large NCDB analysis to determine the appropriateness of treatment as a possible explanation for worse survival outside of the clinical trials. Methods: We included a total of 7190 APL cases reported to NCDB between 2004-2015. Multiple logistic regression analysis was used to evaluate the effect of covariates on probability of multiagent therapy use. Results: Only 64% of total patients received multiagent therapy; 29% received singe agent therapy and 4% received unknown therapy. 3% (n = 207) did not receive any treatment for reasons including early death (n = 8), patient refusal (n = 15), perceived contraindication (n = 12) and unknown reasons (n = 182). Compared to patients > 60 years, younger patients aged 0-18 years (hazard ratio [HR] 3.2, 95% confidence interval [CI] 1.8-5.5, p < 0.001), 19-40 years (HR 1.6, 95% CI 1.03-2.54, p = 0.03) and 41-60 years (HR 1.6, 95% CI 1.3-1.9, p < 0.001) were more likely to receive multiagent chemotherapy. Patients with Medicaid were more likely to receive multiagent therapy compared to those with private insurance (HR 1.2, 95% CI 1.01-1.42, p = 0.04), possibly because patients with Medicaid are younger. The likelihood of receiving multiagent therapy decreased in uninsured patients (HR 0.6, 95% CI 0.5-0.8, p < 0.001). Compared to academic cancer centers, patients treated at community cancer center (HR 0.5, 95% CI 0.3-0.7, p = 0.001), comprehensive community cancer center (HR 0.7, 95% CI 0.6-0.8, p < 0.001)) and integrated network cancer center (HR 0.8, 95% CI 0.6-0-0.9, p = 0.01) were less likely to be treated with multiagent therapy. Lower comorbidity index increased the likelihood of receiving multiagent therapy. The likelihood of receiving multiagent therapy was not influenced by sex, race, annual income, distance traveled to treatment facility and high school education. Conclusions: To our knowledge, this is the first large scale analysis of utilization of multiagent therapy in APL in real world practice. In our study, 3% of patients did not receive treatment, a much smaller proportion of patients compared to acute myeloid leukemia, where a quarter to a third of patients do not receive any chemotherapy (Blood Adv; 2018 (2): 1277–1282). However, 29% of APL patients received suboptimal treatment with single agent therapy. The use of single agent therapy was higher in older adults and those with greater comorbidity. About half of the patients were treated outside of academic centers, which was associated with a higher probability of receiving single agent therapy. Uninsured patients were more likely to receive single agent therapy. Our findings highlight disparity based on insurance and health system factors.