Severe infections in patients with lymphoproliferative diseases treated with new targeted drugs: A multicentric real-world study


Por: Infante, M, Fernandez-Cruz, A, Nunez, L, Carpio, C, Jimenez-Ubieto, A, Lopez-Jimenez, J, Vasquez, L, Del Campo, R, Romero, S, Alonso, C, Morillo, D, Prat, M, Plana, J, Villafuerte, P, Bastidas, G, Bocanegra, A, Serna, A, De Nicolas, R, Marquet, J, Mas-Ochoa, C, Cordoba, R, Garcia-Suarez, J, Comai, A, Martin, X, Bastos-Oreiro, M, Seri, C, Navarro-Matilla, B, Lopez-Guillermo, A, Martinez-Lopez, J, Hernandez-Rivas, J, Ruiz-Camps, I, Grande, C and GELTAMO

Publicada: 1 nov 2021 Ahead of Print: 1 sep 2021
Resumen:
Background Lymphoid neoplasms treatment has recently been renewed to increase antitumor efficacy and conventional chemotherapies toxicities. Limited data have been published about the infection risk associated with these new drugs, therefore this study analyzes the infectious complications in patients with lymphoproliferative diseases (LPD) treated with monoclonal antibodies (obinutuzumab, ofatumumab, brentuximab, nivolumab, or pembrolizumab), BTK inhibitors (ibrutinib and acalabrutinib), PI3K inhibitors (idelalisib) and BCL2 inhibitors (venetoclax). Methods Multicenter retrospective study of 458 LPD patients treated with targeted therapies in real-life setting, in 18 Spanish institutions, from the time of their commercial availability to August 2020. Results Severe infections incidence was 23% during 17-month median follow-up; cumulative incidence was higher in the first 3-6 months of targeted drug treatment and then decreased. The most frequent etiology was bacterial (54%). Nine (6%) Invasive fungal infections (IFI) were observed, in its majority in chronic lymphocytic leukemia (CLL) patients treated predominantly with ibrutinib. Significant risk factors for severe infection were: severe lymphopenia (p = 0.009, OR 4.7, range 1.3-1.7), combined targeted treatment vs single agent treatment (p = 0.014 OR 2.2 range 1.1-4.2) and previous rituximab (p = 0.03 OR 1.8, range 1.05-3.3). Infection-related mortality was 6%. In 22% of patients with severe infections, definitive discontinuation of the targeted drug was observed. Conclusion A high proportion of patients presented severe infections during follow-up, with non-negligible attributable mortality, but infection incidence is not superior to the one observed during the chemotherapy era. In selected cases with specific risk factors for infection, antimicrobial prophylaxis should be considered.

Filiaciones:
Infante, M:
 Hosp Univ Infanta Leonor, Hematol Dept, Gran Via Este 80, Madrid 28031, Spain

Fernandez-Cruz, A:
 Hosp Univ Puerta Hierro Majadahonda, Infect Dis Dept, Madrid, Spain

Nunez, L:
 Hosp Univ Puerta Hierro Majadahonda, Hematol Dept, Madrid, Spain

Carpio, C:
 Hosp Vall de Hebron, Hematol Dept, Barcelona, Spain

Jimenez-Ubieto, A:
 Univ Complutense Madrid, Hematol Dept, CNIO, Hosp 12 Octubre, Madrid, Spain

Lopez-Jimenez, J:
 Hosp Univ Ramon Y Cajal, Hematol Dept, Madrid, Spain

Vasquez, L:
 Hosp Clin Univ Salamanca CAUSA IBSAL, Hematol Dept, Salamanca, Spain

Del Campo, R:
 Hosp Son Llatzer, Hematol Dept, Palma De Mallorca, Spain

Romero, S:
 Hosp Univ & Politecn La Fe, Hematol Dept, Valencia, Spain

:
 Hosp Arnau Vilanova, Hematol Dept, Valencia, Spain

Morillo, D:
 Fdn Jimenez Diaz Univ Hosp, Hlth Res Inst IIS FJD, Hematol Dept, Madrid, Spain

Prat, M:
 Hosp St Pau & Santa Tecla, Hematol Dept, Tarragona, Spain

Plana, J:
 Hosp Vendrell, Hematol Dept, Vendrell, Spain

Villafuerte, P:
 Hosp Univ Principe Asturias, Hematol Dept, Alcala De Henares, Spain

Bastidas, G:
 Inst Invest Biomed August Pi & Sunyer IDIBAPS, Hematol Dept, Barcelona, Spain

Bocanegra, A:
 Hosp Univ Puerta Hierro Majadahonda, Hematol Dept, Madrid, Spain

Serna, A:
 Hosp Vall de Hebron, Hematol Dept, Barcelona, Spain

De Nicolas, R:
 Univ Complutense Madrid, Hematol Dept, CNIO, Hosp 12 Octubre, Madrid, Spain

Marquet, J:
 Hosp Univ Ramon Y Cajal, Hematol Dept, Madrid, Spain

Mas-Ochoa, C:
 Hosp Arnau Vilanova, Hematol Dept, Valencia, Spain

Cordoba, R:
 Fdn Jimenez Diaz Univ Hosp, Hlth Res Inst IIS FJD, Hematol Dept, Madrid, Spain

Garcia-Suarez, J:
 Hosp Univ Principe Asturias, Hematol Dept, Alcala De Henares, Spain

Comai, A:
 Hosp Gen Cataluna, Hematol Dept, Madrid, Spain

Martin, X:
 Hosp Cruces, Hematol Dept, Baracaldo, Spain

Bastos-Oreiro, M:
 Hosp Gen Gregorio Maranon, Hematol Dept, Madrid, Spain

Seri, C:
 Hosp Cent Def Gomez Ulla, Hematol Dept, Madrid, Spain

Navarro-Matilla, B:
 Hosp Univ Puerta Hierro Majadahonda, Hematol Dept, Madrid, Spain

Lopez-Guillermo, A:
 Hosp Clin Barcelona, Hematol Dept, Barcelona, Spain

Martinez-Lopez, J:
 Univ Complutense Madrid, Hematol Dept, CNIO, Hosp 12 Octubre, Madrid, Spain

Hernandez-Rivas, J:
 Hosp Univ Infanta Leonor, Hematol Dept, Gran Via Este 80, Madrid 28031, Spain

Ruiz-Camps, I:
 Hosp Valle De Hebron, Infect Dis Dept, Barcelona, Spain

Grande, C:
 Clin Univ Navarra, Hematol Dept, Madrid, Spain
ISSN: 20457634





Cancer medicine
Editorial
John Wiley and Sons Ltd, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, Estados Unidos America
Tipo de documento: Article
Volumen: 10 Número: 21
Páginas: 7629-7640
WOS Id: 000698522800001
ID de PubMed: 34558211
imagen gold, Green Published

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