Cargando…

1130. Low Risk of Pneumocystis jiroveci Pneumonia in Patients With Waldenstrom’s Macroglobulinemia on Ibrutinib

BACKGROUND: Ibrutinib is a Bruton’s tyrosine kinase inhibitor that is FDA approved for the treatment of chronic lymphocytic leukemia (CLL), mantle cell lymphoma, marginal zone lymphoma, and Waldenstrom’s macroglobulinemia (WM). Fungal infections including Pneumocystis jiroveci pneumonia (PCP) are in...

Descripción completa

Detalles Bibliográficos
Autores principales: Kusztos, Amanda E, Cheng, Matthew P, Gustine, Joshua N, Dubeau, Toni E, Woolley, Ann E, Hammond, Sarah P, Baden, Lindsey R, Castillo, Jorge J, Issa, Nicolas C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255451/
http://dx.doi.org/10.1093/ofid/ofy210.963
_version_ 1783373943442243584
author Kusztos, Amanda E
Cheng, Matthew P
Gustine, Joshua N
Dubeau, Toni E
Woolley, Ann E
Hammond, Sarah P
Baden, Lindsey R
Castillo, Jorge J
Issa, Nicolas C
author_facet Kusztos, Amanda E
Cheng, Matthew P
Gustine, Joshua N
Dubeau, Toni E
Woolley, Ann E
Hammond, Sarah P
Baden, Lindsey R
Castillo, Jorge J
Issa, Nicolas C
author_sort Kusztos, Amanda E
collection PubMed
description BACKGROUND: Ibrutinib is a Bruton’s tyrosine kinase inhibitor that is FDA approved for the treatment of chronic lymphocytic leukemia (CLL), mantle cell lymphoma, marginal zone lymphoma, and Waldenstrom’s macroglobulinemia (WM). Fungal infections including Pneumocystis jiroveci pneumonia (PCP) are increasingly reported in patients with CLL and lymphoma on ibrutinib possibly due to the off-target effect of ibrutinib on the adaptive immune system. Whether this increased risk is due to the effect of ibrutinib alone or in combination with immune dysregulation due to underlying malignancy is unknown. The purpose of this study was to assess the incidence of PCP in patients with WM on ibrutinib therapy. METHODS: A retrospective cohort study was performed of all patients with WM who initiated ibrutinib monotherapy at Dana-Farber Cancer Institute between July 1, 2015 and January 30, 2018. Baseline characteristics, laboratory parameters, previous and concomitant malignancy treatment regimens, and antimicrobial medications were collected by chart review. Patients were followed until April 1, 2018 for the development of PCP. RESULTS: There were a total of 106 patients with WM on ibrutinib during the study period. Sixty-one (58%) were male, and the median age at initiation of ibrutinib was 69 years (range 43 – 89). Forty-six patients (43%) received prior therapy for WM, with a median of two previous treatment courses (range 1–6). Fourteen patients (13%) were on PCP prophylaxis for a combined duration of 8 person-years. No cohort patient developed PCP during the study period, which included 146 person-years of ibrutinib exposure. Three patients (3%) died due to disease progression (n = 2) and E. coli sepsis (n = 1). CONCLUSION: Patients with WM on ibrutinib monotherapy appear to have a different infectious risk profile than patients with CLL or lymphoma and do not have a high risk of developing PCP. These data suggest that PCP prophylaxis is likely not beneficial for patients with WM on ibrutinib. DISCLOSURES: M. P. Cheng, Royal College of Physicians and Surgeons of Canada: Member, Salary. S. P. Hammond, Merck: Investigator, Research support. J. J. Castillo, Pharmacyclics: Consultant and Grant Investigator, Consulting fee and Research grant. N. C. Issa, GSK: Investigator, Research grant. Merck: Investigator, Research grant. Akros Pharma: Consultant, Consulting fee.
format Online
Article
Text
id pubmed-6255451
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-62554512018-11-28 1130. Low Risk of Pneumocystis jiroveci Pneumonia in Patients With Waldenstrom’s Macroglobulinemia on Ibrutinib Kusztos, Amanda E Cheng, Matthew P Gustine, Joshua N Dubeau, Toni E Woolley, Ann E Hammond, Sarah P Baden, Lindsey R Castillo, Jorge J Issa, Nicolas C Open Forum Infect Dis Abstracts BACKGROUND: Ibrutinib is a Bruton’s tyrosine kinase inhibitor that is FDA approved for the treatment of chronic lymphocytic leukemia (CLL), mantle cell lymphoma, marginal zone lymphoma, and Waldenstrom’s macroglobulinemia (WM). Fungal infections including Pneumocystis jiroveci pneumonia (PCP) are increasingly reported in patients with CLL and lymphoma on ibrutinib possibly due to the off-target effect of ibrutinib on the adaptive immune system. Whether this increased risk is due to the effect of ibrutinib alone or in combination with immune dysregulation due to underlying malignancy is unknown. The purpose of this study was to assess the incidence of PCP in patients with WM on ibrutinib therapy. METHODS: A retrospective cohort study was performed of all patients with WM who initiated ibrutinib monotherapy at Dana-Farber Cancer Institute between July 1, 2015 and January 30, 2018. Baseline characteristics, laboratory parameters, previous and concomitant malignancy treatment regimens, and antimicrobial medications were collected by chart review. Patients were followed until April 1, 2018 for the development of PCP. RESULTS: There were a total of 106 patients with WM on ibrutinib during the study period. Sixty-one (58%) were male, and the median age at initiation of ibrutinib was 69 years (range 43 – 89). Forty-six patients (43%) received prior therapy for WM, with a median of two previous treatment courses (range 1–6). Fourteen patients (13%) were on PCP prophylaxis for a combined duration of 8 person-years. No cohort patient developed PCP during the study period, which included 146 person-years of ibrutinib exposure. Three patients (3%) died due to disease progression (n = 2) and E. coli sepsis (n = 1). CONCLUSION: Patients with WM on ibrutinib monotherapy appear to have a different infectious risk profile than patients with CLL or lymphoma and do not have a high risk of developing PCP. These data suggest that PCP prophylaxis is likely not beneficial for patients with WM on ibrutinib. DISCLOSURES: M. P. Cheng, Royal College of Physicians and Surgeons of Canada: Member, Salary. S. P. Hammond, Merck: Investigator, Research support. J. J. Castillo, Pharmacyclics: Consultant and Grant Investigator, Consulting fee and Research grant. N. C. Issa, GSK: Investigator, Research grant. Merck: Investigator, Research grant. Akros Pharma: Consultant, Consulting fee. Oxford University Press 2018-11-26 /pmc/articles/PMC6255451/ http://dx.doi.org/10.1093/ofid/ofy210.963 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Kusztos, Amanda E
Cheng, Matthew P
Gustine, Joshua N
Dubeau, Toni E
Woolley, Ann E
Hammond, Sarah P
Baden, Lindsey R
Castillo, Jorge J
Issa, Nicolas C
1130. Low Risk of Pneumocystis jiroveci Pneumonia in Patients With Waldenstrom’s Macroglobulinemia on Ibrutinib
title 1130. Low Risk of Pneumocystis jiroveci Pneumonia in Patients With Waldenstrom’s Macroglobulinemia on Ibrutinib
title_full 1130. Low Risk of Pneumocystis jiroveci Pneumonia in Patients With Waldenstrom’s Macroglobulinemia on Ibrutinib
title_fullStr 1130. Low Risk of Pneumocystis jiroveci Pneumonia in Patients With Waldenstrom’s Macroglobulinemia on Ibrutinib
title_full_unstemmed 1130. Low Risk of Pneumocystis jiroveci Pneumonia in Patients With Waldenstrom’s Macroglobulinemia on Ibrutinib
title_short 1130. Low Risk of Pneumocystis jiroveci Pneumonia in Patients With Waldenstrom’s Macroglobulinemia on Ibrutinib
title_sort 1130. low risk of pneumocystis jiroveci pneumonia in patients with waldenstrom’s macroglobulinemia on ibrutinib
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255451/
http://dx.doi.org/10.1093/ofid/ofy210.963
work_keys_str_mv AT kusztosamandae 1130lowriskofpneumocystisjirovecipneumoniainpatientswithwaldenstromsmacroglobulinemiaonibrutinib
AT chengmatthewp 1130lowriskofpneumocystisjirovecipneumoniainpatientswithwaldenstromsmacroglobulinemiaonibrutinib
AT gustinejoshuan 1130lowriskofpneumocystisjirovecipneumoniainpatientswithwaldenstromsmacroglobulinemiaonibrutinib
AT dubeautonie 1130lowriskofpneumocystisjirovecipneumoniainpatientswithwaldenstromsmacroglobulinemiaonibrutinib
AT woolleyanne 1130lowriskofpneumocystisjirovecipneumoniainpatientswithwaldenstromsmacroglobulinemiaonibrutinib
AT hammondsarahp 1130lowriskofpneumocystisjirovecipneumoniainpatientswithwaldenstromsmacroglobulinemiaonibrutinib
AT badenlindseyr 1130lowriskofpneumocystisjirovecipneumoniainpatientswithwaldenstromsmacroglobulinemiaonibrutinib
AT castillojorgej 1130lowriskofpneumocystisjirovecipneumoniainpatientswithwaldenstromsmacroglobulinemiaonibrutinib
AT issanicolasc 1130lowriskofpneumocystisjirovecipneumoniainpatientswithwaldenstromsmacroglobulinemiaonibrutinib