Adverse Events Among Patients with Hairy Cell Leukemia Treated with Purine Nucleoside Analogs in the United States

Introduction: Purine nucleoside analogs (PNAs) are the recommended first-line treatment in patients with hairy cell leukemia (HCL) owing to their efficacy. However, because of the rarity of this disease, little is known about clinically significant adverse events (AEs) outside of previously performed clinical trials. This retrospective claims-based study of patients treated in the current era of improved supportive care assessed the incidence and prevalence rates of AEs associated with PNA use and healthcare resource utilization (HRU) among patients with HCL enrolled in the Truven MarketScan Commercial Claims and Encounters and the Medicare Supplemental databases.

Methods: Adults (≥18 years old) diagnosed with HCL (≥2 medical claims ≥30 days apart) between January 1, 2006 and December 31, 2015 were included in the study. All patients had ≥1 claim for PNA therapy (cladribine or pentostatin ± rituximab) after the HCL diagnosis date and the 1st prescription claim was defined as the index date. Continuous health plan enrollment for ≥6 months pre- (baseline period) and ≥12 months post-index date (follow-up period) was required. Patients treated with a PNA during the baseline period were excluded. Incidence rate was defined as the number of new cases of an AE during the follow-up period divided by the number of patients at risk (patients without any evidence of the adverse event in the 6-month baseline period). Prevalence rate was defined as the number of all AEs (existing cases during the baseline period and new cases during the follow-up period) divided by the total number of patients. Incidence and prevalence rates were calculated as rate per 1000 patient-years at risk. To evaluate the HRU, PNA-treated patients with HCL were categorized based on occurrence of highest AE during the follow-up period. Generalized linear model (GLM) compared HRU during the 12-month follow-up, adjusting for demographic, clinical characteristics, and baseline total healthcare costs.

Results: In total, 647 PNA-treated patients with HCL were identified. Mean age (standard deviation) was 57.1 (12.2) years. Most patients were men (81.5%) and resided in the southern USA (32.2%). Over the 12-month follow-up period, 87.2% of the PNA-treated patients developed at least one AE. PNA-related AEs with the highest incidence rate were myelosuppression, anemia, and skin toxicities. The prevalence rate showed a similar trend for PNA-related AEs. Infectious complications including opportunistic infections were seen at a high rate (Table 1). The incidence and prevalence of infectious complications overall were 23.5% and 39.3% (235 and 393 per 1000 patient-years), respectively. Patients who developed myelosuppression had a higher rate of hospitalization compared with those who did not (47.4% vs 12.2%; p<0.0001) and had a longer inpatient length of stay (LOS) (3.4 vs 0.8 [days]; p=0.001). A higher proportion of patients who developed opportunistic infections were hospitalized compared with those who did not (53.7% vs 30.8%; p=0.025) and had a longer inpatient LOS (5.4 vs 2.4 [days]), although this was not statistically significant (p=0.138).

Conclusion: This large claims-based dataset of patients with HCL treated with PNAs shows that a substantial proportion of patients developed AEs, including myelosuppression (most frequent) and infectious complications. Because of the nature of the data set, information regarding mortality is not currently available. However, infections due to myelo- and immunosuppression are known to be the most frequent causes of death in this patient population. These findings indicate a need for larger studies evaluating the outcomes of patients with HCL treated with approved therapies to understand better their short- and long-term toxicities, as well as for the development of therapies with lower risks of myelo- and immunosuppression.

View largeDownload slide

View largeDownload slide

Close modal