1719. Incidence and Characterization of Invasive Fungal Infections (IFIs) in Patients with Chronic Lymphocytic Leukemia (CLL) Treated with Ibrutinib (IBR)

Abstract

BackgroundIBR is a Bruton’s tyrosine kinase inhibitor, and plays a key role in the treatment of CLL. In randomized clinical trials, <1% of IBR-treated CLL patients developed IFIs. However, several IFIs were reported with real-life use of IBR.MethodsThis is a retrospective observational study of all CLL patients (> 18 years) treated with IBR (2/2014–8/2018) at MD Anderson Cancer Center. We excluded patients with active IFI (proven and probable, EORTC/MSG criteria) at the start of IBR and patients with <6 months of follow-up.ResultsOf the 821 CLL IBR-treated patients, 24 developed probable or proven IFI (2.9%). Of these infections, 21 occurred within 30 days (d) of last IBR dose, while 3 IFIs occurred at 94, 135 and 221 d post IBR, respectively. The majority of patients with IFI were male (83%) with a median age of 66 years at IFI diagnosis. The median prior lines of therapy for CLL was 1 (range 0–7), with 29% receiving IBR as frontline treatment. Five patients had evidence of Richter’s transformation at the time of IFI diagnosis, while two patients had prior stem cell transplant. The average time from start of IBR to diagnosis of IFI was 338 d, with only 7 cases of IFI within the first 3 months of IBR. The majority of IFIs were proven/probable aspergillosis (63%), including 9 cases of Aspergillus fumigatus. The remaining infections consisted of Cryptococcus neoformans (21%), Fusarium spp. (8%), with one case each of candidiasis, histoplasmosis, mucormycosis, and Pneumocystis jiroveci pneumonia. Three patients had evidence of poly-fungal IFI. The sites of infection were pulmonary (88%), blood (13%), CNS (13%), and sinus (8%). Five patients were diagnosed with disseminated IFI, including Cryptococcus spp. (2 cases), Rhizopus spp., Aspergillus spp., and Candida spp. The 42-day mortality rate post IFI diagnosis was 25%.ConclusionWe report the largest single-center cohort of CLL patients on IBR to date. The IFI incidence of 2.9% (24/821) is consistent with most previous reports estimating a 0.5–4% incidence. In contrast to published reports, close to 1/3 of our patients with IFI received IBR as frontline therapy and most IFIs (71%) were diagnosed > 3 months after starting IBR. We are currently conducting a case–control comparison with IBR–treated CLL patients with no infection to uncover risk factors associated with IFIs in these patients.DisclosuresSamuel L. Aitken, PharmD, Melinta Therapeutics: Grant/Research Support, Research Grant; Merck, Sharpe, and Dohme: Advisory Board; Shionogi: Advisory Board.