There is a lack of published estimates of the occurrence of major symptoms and toxicities (SxTox events) and associated costs during AML episodes of care in real-world data. This analysis evaluated the frequency and cost implication of SxTox events in a US commercially insured population with AML during these episodes of care: high intensity chemotherapy (HIC), low intensity chemotherapy (LIC), hematopoietic stem cell transplant (HSCT) and relapsed-refractory (R/R) treatment.


A large US healthcare claims database (PharMetrics Plus™) was linked to charge detail master (CDM) hospital data, to identify incident adult patients (≥ 2 outpatient or ≥ 1 inpatient claim with an AML diagnosis) between 1/1/2008 and 3/31/2016. Patients had continuous health plan enrolment for ≥ 6 months pre and ≥ 3 months post the first diagnosis date (index) to assure collection of representative data. Episodes evaluated included HIC induction (inpatient high dose cytarabine+anthracycline use within 3 months post-index), HIC consolidation (cytarabine +/- anthracycline use within 2 months following a prior HIC), LIC (receipt of low-intensity or less toxic chemotherapy in the outpatient setting within 3 months post-index), HSCT (a record of transplant specific diagnosis/procedure codes) and R/R patients (ICD-9 diagnosis code of 205.02 for relapsed AML, or a new line of therapy (new agent or re-initiation of treatment after 90-day gap), after a prior treatment of HIC, LIC, or HSCT). SxTox events of interest observed during episodes were identified via diagnostic and treatment codes and reported as frequencies. A generalized linear model (GLM) was used to assess the contribution of events to total episode costs while controlling for age, gender and Charlson Comorbidity Index (CCI) score.


The study sample consisted of 1,542 HIC induction (mean age 47.0 years; mean follow-up 2.1 months), 591 consolidation (mean age 47.0 years; mean follow-up 1.5 months), 628 LIC (mean age 64.9 years; mean follow-up 2.0 months), 1,000 HSCT (mean age 51.4 years; mean follow-up 6.4 months) and 910 R/R patients (mean age 52.3 years; mean follow-up 12.6 months). The SxTox events most frequently observed during HIC induction episodes were blood and lymphatic system disorders (98.8%), infections (91.1%), gastrointestinal (GI) disorders (69.1%), nervous system disorders (56.2%), cardiovascular (CV) disorders (44.6%), bleeding (39.0%), and skin and subcutaneous tissue disorders (31.2%). Most HIC consolidation patients experienced blood and lymphatic system disorders (96.4%) and infections (89.5%); while other SxTox events were less frequent except bleeding event rates were higher (73.6%) than during induction (Table 1). LIC patients experienced lower rates of SxTox events compared to HIC induction; frequently observed events were blood and lymphatic system disorders (84.1%), infections (64.3%), bleeding (54.0%), GI (47.5%), CV (36.5%), and renal disorders (27.9%). HSCT patients had similar SxTox event rates as those occurring during HIC induction, while the following SxTox events were more frequent: GI disorders, bleeding events, renal, and CV disorders. R/R patients had a higher occurrence and wider range of high frequency SxTox events, including blood and lymphatic system disorders (96.8%), infections (96.4%), GI disorders (83.2%) bleeding (68.9%), CV disorders (67.5%), nervous system disorders (62.7%), skin and subcutaneous tissue disorders (36.6%), renal disorders (35.6%), and vascular disorders (31.5%). Multivariate GLM results revealed that R/R episodes were sensitive to the occurrence of any SxTox events, which significantly increased costs during R/R episodes, while the occurrence of SxTox events had a mixed impact on increasing total costs in other episodes. CV disorders consistently increased total costs in the following episodes: HIC induction (22% higher; p<0.001), consolidation (23% higher; p=0.005), LIC (36% higher; p<0.001), and R/R episodes (32% higher; p<0.001).


This analysis observed that major symptoms and toxicities are associated with a significant clinical and economic burden during AML treatment episodes in the US. These SxTox events had the broadest impact on R/R AML patients which may suggest R/R AML patients are less tolerant of currently available treatments. Therapies with lower toxicity would fill an unmet need, especially in R/R AML.


Pandya: Astellas Pharma Global Development: Employment. Chen: QuintilesIMS: Employment. Wilson: Astellas Pharma Global Development: Employment. Groves: QuintilesIMS: Employment. Horvath: Astellas Pharma Global Development: Employment. Wade: QuintilesIMS: Employment.

Author notes


Asterisk with author names denotes non-ASH members.

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