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: 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 use of adequate prophylactic and/or monitoring strategies are essential in preventing serious OIs in this population.
A. Nevett-Fernandez, None
D. Prestes, None
A. Liakos, None
A. Woolley, None
S. Hammond, None
J. Brown, Pharmacyclics, Janssen, Celgene, Gilead, Infinity, Genentech, and Pfizer, Roche and Sun BioPharma, Janssen, Gilead, Sun BioPharma, and Pfizer: Consultant , Consulting fee
L. Baden, None
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