Economic Burden Associated with Adverse Events of Special Interest (AESI) in Patients with Relapsed Acute Lymphoblastic Leukemia (ALL) in the US

Introduction

Acute lymphoblastic leukemia (ALL) is a type of cancer in which body overproduces lymphoblasts in the bone marrow (National Cancer Institute, 2016). Relapsed Philadelphia chromosome-negative (Ph-) B-cell ALL patients are extremely ill, and further compromised by treatment; hence, complications due to either the disease or the treatment are very common and often managed with inpatient admission. Infections, cytopenia and gastrointestinal (GI) toxicity events are often mentioned as important adverse events of special interest (AESI) among ALL patients (Hummel et al., 2016; Offidani et al., 2004, Schmiegelow et al., 2017) with detrimental impact on patients' quality of life. However, the economic burden of these events is not well documented in the published literature.

Objective

The aim of this study is to quantify the rates and economic burden of infections, cytopenia, and GI toxicity events among adults with relapsed Ph- ALL in the US.

Methods

This was a retrospective cohort study using Truven Health MarketScan^® Commercial and Medicare Supplemental Databases. Patients with ≥1 inpatient claims or ≥2 non-diagnostic outpatient claims at least 30 days apart for relapsed ALL diagnosis (ICD-9-CM 204.02, ICD-10-CM C91.02) during 4/1/2009 - 10/31/2016 were extracted. All patients were required to have ≥1 hospitalization with diagnosis-related group in 834-839 on or after the first relapsed ALL diagnosis (index date was the admission date for the first hospitalization), were ≥18 years old on index date, and had ≥6 months of continuous enrollment prior to index date. Patients with medications for Ph+ or T-Cell ALL anytime during the study period were excluded. Patients were followed until the earliest event of inpatient death, end of continuous enrollment, end of the study period (10/31/2016), or 100 days post-index. AESI was defined as infections (including bacteremia, febrile neutropenia, line infections, pneumonia and sepsis), cytopenia (including anemia, neutropenia, thrombocytopenia and other cytopenia), or GI toxicities (including nausea/vomiting, diarrhea, gastritis/duodenitis, GI bleeding and mucositis/stomatitis) during the follow-up period. Outcomes included proportion of patients with AESI and AESI-related healthcare costs for any AESI and specific AESI categories and events. The AESI-related costs were calculated among those with at least one AESI and were the total costs accumulated during the follow-up after index date at the patient level. Costs were sum of the plan paid amount and out-of-pocket amount in 2016 US dollars.

Results

A total of 400 relapsed Ph- ALL patients were identified and 92.5% of them (mean age: 41.9 years; male: 63.0%; mean Charlson comorbidity index: 3.0) experienced at least one AESI during a mean (median) follow-up period of 84 (100) days. Among all the relapsed Ph- ALL patients with AESI, 64.6% had infections, 94.6% had cytopenia, and 46.2% had GI toxicity events (Table 1). The most frequent infection event observed was sepsis (40.0%); the most frequent cytopenia events were neutropenia (68.4%) and anemia (63.0%); and nausea/vomiting (26.8%) was the most frequent GI toxicity event. The total average (SD; median) AESI-related healthcare costs during 100 days post index date was $197,213 ($308,551; $105,731) (Table 1). Across all patients with AESI, the mean (SD) number of AESI-related hospitalizations was 2.0 (1.3), with a total mean (SD; median) length of stay of 32.2 (26.0; 27.0) days during the follow-up. Mean (SD; median) healthcare costs were highest for infection-related events ($164,461 [$347,083; $64,528]), followed by cytopenia ($125,210 [$165,141; $67,475]) and GI toxicity-related events ($11,652 [$40,231; $1,349]). At the specific event level, average healthcare costs were highest for sepsis ($204,151 [$412,572; $79,853]) and other cytopenia-related events ($98,900 [$143,961; $39,777]).

Conclusions

Infections, cytopenia, and GI toxicity events affect the vast majority of relapsed Ph- ALL patients. The economic burden associated with AESI is substantial, with infections the most expensive AESI, followed by cytopenia and GI toxicity. One limitation of this study is that we couldn't separate the AESI due to treatment from those due to the disease itself. Nonetheless, new therapies that can improve the outcomes of the relapsed Ph- ALL patients while offering a favorable safety profile are needed.

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