Adverse events and estimated costs with the combination of ipilimumab and nivolumab in metastatic melanoma patients.
e21529 Background: The combination of ipilimumab and nivolumab in metastatic melanoma patients increases response rates (RR) and survival outcomes. As checkpoint inhibitors bear a significant financial impact on the healthcare system, we performed a study that addresses the global costs of the treatment, focusing on immune-related adverse event (irAE) management costs. Methods: We conducted a retrospective analysis of 62 metastatic melanoma patients treated with ipilimumab and nivolumab at the Oncology Department of Lausanne University Hospital (CHUV) between June 1, 2016 and August 31, 2019. The frequency of irAEs, the duration, management, and outcomes were evaluated. All melanoma-specific costs were analyzed by mining the electronic healthcare record and billing data of the hospital. Results: The median follow-up was 32 months (range 20-1066 days). In our cohort, 54/62 (87%) patients presented at least one irAE, and 22/62 (35%) presented a grade 3 irAE. One patient died from an irAE (pneumonitis). The most common irAEs were diarrhea 23/62 (37%) any grade, 8/62 (13%) grade 3-4; hepatitis 22/62 (36%) any grade, 9/62 (15%) grade 3-4; and skin rash 21/62 (34%) any grade, 6/32 (10%) grade 3-4. The overall response rate was 29/62 (47%), with 15/62 (24%) of complete response (CR) and 14/62 (23%) of partial response (PR). The majority of patients who had a CR 13/15 (87%) and 20/28 (71%) of overall responders presented a grade 3-4 toxicity, and there were no responses in patients without toxicity. However, toxicity does not imply response, as only 29/54 (54%) of patients with toxicity (any grade) and 20/31 (65%) (grade 3-4) responded. The toxicity costs represent only 3% on average of the total expenses per patient. The most significant contributions were medication costs (44%) and disease costs (39%, mainly disease-related hospitalization costs). Patients with a CR had the lowest global cost per week (2,860 USD, converted from CHF) despite the associated toxicities and patients who had progressive disease, the highest one (9,999 USD). Except for the one patient who had a grade 5 toxicity (7,472 USD/week), we observe that less severe toxicity grades (11,603 USD/week for grade 1), or even the absence of toxicity (12,266 USD/week), are associated to higher median costs per week (against 4,039 USD/ week for grade 4 and 3,524 USD/week for grade 3). Conclusions: The cost of toxicities was unexpectedly small (only 3%) compared to the total costs, especially medication costs (44%). Also, patients with a higher degree of toxicity had lower costs and better outcomes.