The Cost of Managing Pleural Effusion Associated with Dasatinib in CML Patients Post Imatinib Failure.

Background: Recent follow-up data from dasatinib at a large cancer center suggests that pleural effusion events occur in up to 35% of patients, emerging as late as 24 months into therapy, and require additional medical resource use beyond the typical routine care. This study aims to apply economic costs to the medical resource utilization involved with treating pleural effusions associated with dasatinib. Methods: The costs of managing pleural effusions were estimated by applying standard cost data to medical resource utilization reported for 48 patients with dasatinib-related pleural effusions at one large cancer center (Quintas-Cardama et al, ASH 2006). Relevant CPT codes and median fees for outpatient procedures and office visits were retrieved from the 2006 Ingenix National Fee Analyzer. Cost of inpatient management of pleural effusions with chest tubes or other procedures were obtained from the medical literature (Putnam et al, 2000). Clinical expert input was used to supplement the literature related to assumptions of frequency of office visits and chest X-rays. Based on the above, the following key assumptions were made: 100% of patients incurred two additional physician visits, two chest x-rays, and a course of diuretics; 30% received steroids; 24% had recurrent effusions; 19% required 3 thoracentesis outpatient procedures; 5% were managed as inpatients with chest tube; and 4% required Denver shunts as inpatients. All costs were inflated to 2006 US prices. Results: Fifty-eight percent of pleural effusions reported at the cancer center involved ≤25% of one lung volume and were managed medically including diuretics and steroids. Costs for this medically managed group were $619 per episode, including physician office visits, chest X-rays and medications. Forty-two percent of pleural effusions were more significant, involving 26% to >75% of one lung volume, with half of those patients requiring invasive procedures. The cost of invasive procedures for inpatient management of pleural effusions was $10,130 for a chest tube and $14,475 with a pleural catheter. The cost of invasive outpatient management of pleural effusions ranged from $680 for ultrasound thoracentesis to $4,387 for pleural catheter. The average projected cost of treating a pleural effusion adverse event (including all severity levels) ranged from $1,694 to $3,882, depending on whether outpatient thoracentesis occurred or placement of outpatient pleural catheter was utilized. Important cost drivers included management of recurrent effusions. Conclusion: This economic analysis based on actually observed treatment patterns suggests that the management of pleural effusions with dasatinib is costly and requires intensive resource utilization. Development of pleural effusions with dasatinib poses a significant challenge to physicians, as they cannot be predicted, the time of onset is variable, and management may require repeat invasive procedures and possible complications. This economic analysis is likely conservative in that it did not include the cost of platelet transfusions that may be needed to perform thoracentesis, or the potential complications of hypokalemia and QTcF prolongation with the use of diuretics. Effective tyrosine kinase inhibitors with lower rates of pleural effusions may represent a clinically and economically valuable alternative for imatinib-resistant or -intolerant CML patients.