PS1283 CLINICAL IMPLICATIONS OF AZOLE-RESISTANT VERSUS AZOLE-SUSCEPTIBLE INVASIVE ASPERGILLOSIS IN HEMATOLOGICAL MALIGNANCY (CLARITY) – A MULTICENTER STUDY
Authors: O.A. Cornely, D. Seidel, D. Arenz, J.F. Meis, J.J. V. Vehreschild, Z. Racil, O. Blennow, K. Lagrou, J. Maertens, A. Reséndiz Sharpe, C. Lass-Flörl, Y. Le Govic, A. Ostojic, W.J. Melchers, M.J. Vehreschild, P.E. Verweij
Journal: HemaSphere (2019)

Background: The clinical development of checkpoint inhibitor-based immunotherapy has ushered in an exciting era of anticancer therapy. Despite of many reports on anti PD-1 antibody therapy for the treatment of Hodgkin's lymphoma (HL), risk of infection among patients receiving nivolumab is still unknown. We are the first to present the real-life data on infection complications in large cohort of r/r HL after nivolumab (nivo) therapy. Aims: Our aim was to study the epidemiology of infection complications in r/r HL adult patients during one year of salvage therapy with nivo in CIC 725. Methods: Between 2016 and 2018 years 112 patients with r/r HL were observed and treated with nivolumab (3 mg/kg) in CIC 725. The median age was 31 y.o. (13–62 years). The median number of nivolumab courses received was 20 (range, 1–30). 18 patients underwent allo-HSCT after therapy of nivolumab. The median follow-up period was 1,4 years (1 month-2,6 year). Outcome analysis considered events at one year after first nivolumab administration and were censored at the date of allo-HSCT or auto-HSCT. Infections were identified by reviewing patient clinical, laboratory data and imaging studies. All patients had a standard anti-infective prophylaxis and treatment according to the international guidelines. Results: During salvage treatment with nivolumab of r/r HL in 11 (10%) patients were documented infection episodes (n = 16): bacterial infections – 37,5% (n = 6), invasive fungal diseases (IFD) – 25% (n = 4) and viral infections – 37,5% (n = 6). The median time to infection episodes was 98 days (12–365) after first nivolumab administration. Incidence of bacterial infections in study cohort was 5,3% (n = 6). Two patients developed pneumonia, others met in one: sinusitis, meningitis cause by Listeria meningitis, colitis and gonitis. Incidence of viral infections was 5,3% (n = 6): pneumonia associated with HHP-6 and CMV in 50% and generalized infections in 50% caused by HSV-1,2 and HHV-6. Invasive fungal diseases were diagnosed in 3,6% patients (n = 4). The main etiology agent was Aspergillus spp. in 50%. Primary chemoresistant disease before nivolumab therapy was the only risk factor of infection complications during treatment of r/r HL (p = 0,029). Overall survival (OS) at 1 year after first nivolumab administration in study cohort was 96,5%. The only one death was attributed to infection, patient died due to sepsis unknown etiology. Summary/Conclusion: Incidence of infectious complications in r/r HL treated with nivolumab was 10% with the median time of onset – 98 days. Etiology of infectious complications presented by bacterial infections –37,5%, invasive fungal diseases – 25% and viral infections – 37,5%. Primary chemoresistance was a risk factor for infection complications. Wherewith infections could be managed successfully and carry favorable prognosis.