Severe infections in patients with lymphoproliferative diseases treated with new targeted drugs: A multicentric real-world study
Maria Stefania Infante 1 , Ana Fernández-Cruz 2 , Lucia Núñez 3 , Cecilia Carpio 4 , Ana Jiménez-Ubieto 5 , Javier López-Jiménez 6 , Lourdes Vásquez 7 , Raquel Del Campo 8 , Samuel Romero 9 , Carmen Alonso 10 , Daniel Morillo 11 , Margarita Prat 12 , José Luis Plana 13 , Paola Villafuerte 14 , Gabriela Bastidas 15 , Ana Bocanegra 3 , Ángel Serna 4 , Rodrigo De Nicolás 5 , Juan Marquet 6 , Carmen Mas-Ochoa 10 , Raúl Cordoba 11 , Julio García-Suárez 14 , Alessandra Comai 16 , Xavier Martín 17 , Mariana Bastos-Oreiro 18 , Cristina Seri 19 , Belén Navarro-Matilla 3 , Armando López-Guillermo 20 , Joaquín Martínez-López 5 , José Ángel Hernández-Rivas 1 , Isabel Ruiz-Camps 21 , Carlos Grande 22 , Grupo Español de Linfomas y Trasplante Autólogo de Medula Ósea (GELTAMO)
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.