Opportunistic Infections (OIs) in Patients with Hematologic Malignancies (HM) Treated with Bruton’s Tyrosine Kinase (BTK) and Phosphoinositide 3 Kinase (PI3K) Inhibitors: An 8-Year Retrospective Cohort Study

BACKGROUND: BTK and PI3K inhibitors are increasingly used for treatment in patients with HM. OIs when these agents were used as first line therapy signaled an increased level of immunosuppression beyond what was expected from the mechanism of action of these drugs. The epidemiology of OIs in the setting of BTK and PI3K inhibitor use has not been characterized. METHODS: We retrospectively studied a cohort of patients with HM who received BTK (ibrutinib, acalabrutinib, spebrutinib) or PI3K (idelalisib, duvelisib, TGR-1202) inhibitors as part of clinical trials at our center between March 2008 and November 2016. Patients were followed up until April 30, 2017. Incident infectious complications were recorded. Cohort baseline characteristics, underlying malignancy, stage of disease, type of therapy and use of antimicrobial prophylaxis were recorded. RESULTS: 148 patients who received BTK or PI3K inhibitors as first or second line therapy were included in the study. Median age was 64.5 years, 32% were female, 95.9% had chronic lymphocytic leukemia (CLL), 4.1 % had Non-Hodgkin Lymphoma (NHL). Sixty-three percent received BTK inhibitors and 37% received PI3K inhibitors as first line therapy. Pneumocystis and HSV/VZV prophylaxis were used in 82.4% and 85.8% of patients, respectively. Twenty-seven OIs occurred in 24 patients. The most common OIs were pneumocystosis (7), aspergillosis (5) HSV (3), VZV (3), CMV (2), Cryptococcal meningitis (2), candidiasis (2) and other invasive mold infections (3). Seventy-one patients (48%) had infectious episodes not considered OIs. Median time to onset of OIs after start of therapy was 78 days (range, 6–323). Twelve OIs (8.1 %) occurred after first line therapy with BTK inhibitors, 11 OIs (7.4 %) occurred after first line PI3K inhibitors. CONCLUSION: The use of BTK and PI3K inhibitors as first or second line treatment of CLL or NHL are associated with incident OIs. Clinical awareness of these complications and the use of adequate prophylactic and/or monitoring strategies are essential in preventing serious OIs in this population. DISCLOSURES: J. Brown, Pharmacyclics, Janssen, Celgene, Gilead, Infinity, Genentech, and Pfizer, Roche and Sun BioPharma, Janssen, Gilead, Sun BioPharma, and Pfizer: Consultant, Consulting fee; F. Marty, Astellas Pharma US: Consultant and Grant Investigator, Consulting fee and Grant recipient; Chimerix: Consultant and Grant Investigator, Consulting fee and Grant recipient; Fate Therapeutics: Scientific Advisor, Consulting fee; Gilead Sciences: Consultant and Grant Investigator, Consulting fee and Grant recipient; LFB: Consultant, Consulting fee; Merck: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Grant recipient; Roche Molecular Systems: Consultant, Consulting fee; Shire: Consultant and Grant Investigator, Consulting fee and Grant recipient