Naslov
Ibrutinib therapy is associated with serious infections in patients with B-cell malignanciesa

Autori
Mišura Jakobac, Karla ; Milunović, Vibor ; Kursar, Marin ; Mandac Rogulj, Inga ; Ostojić Kolonić, Slobodanka ; Radić-Krišto, Delfa

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
HemaSphere / - , 2019, 869-869

Skup
24th Congress of the European Hematology Association

Mjesto i datum
Amsterdam, Nizozemska, 13.06.2019. - 16.06.2019

Vrsta sudjelovanja
Ostalo

Vrsta recenzije
Recenziran

Ključne riječi
Ibrutinib, Kronična limfocitna leukemija, Limfom plaštene zone, infekcije
(Ibrutinib, Chronic lymphocytic leukemia, Mantle cell lymphoma, Infections)

Sažetak
Background: Ibrutinib is an irreversible inhibitor of Bruton tyrosine kinase (BTK). Recently, ibrutinib has become available in Croatia for chronic lymphocytic leukemia (CLL) with del17p aberration or in early relapse and for relapsed/refractory mantle cell lymphoma (MCL) pretreated with bendamustine and rituximab. BTK inhibition can lead to immunosuppression through B- and T-cell inhibition resulting in an increase in infections. In literature, systematic meta- analyses have shown higher incidence of infections in B-cell malignancies treated with ibrutinib, however the results for CLL are diverse. Aims: The main aim of this retrospective study was to retrospectively review all infections associated with ibrutinib in patients treated with B-cell malignancies and characterized the grade and possible predisposing factors at single center institution. Methods: We retrospectively reviewed the medical charts for all patients treated with ibrutinib in era from 2015-2018 to estimate the rate and grade of infections and possibly underlying factors predisposing these patients to infections. Results: A total number of patients included was 32, mainly the patients treated for CLL (28). Median line of previous therapies was 2 with only two patients being treatment naïve. The dosage of ibrutinib was according to the standard of care with median exposure to ibrutinib being 8.5 months. Any grade of infections occurred in 41.9% (N = 18) of our sample with median time to first infection being 82.5 days. The most common type of infection was sepsis (33.3%) followed by pneumonia (22.2%). The specific microbiological agents were isolated in 8 patients. Most of infections were mild (grade I/II according to NCI CTCAE nomenclature) estimated to be 41.2% in our sample. Grade III-IV infections occurred in 35.3% of sample and grade V infections occurred in 4 patients. It is important to note that re- infection occurred in 4 patients. Ibrutinib therapy was temporally withdrawn in 9 patients with median time off therapy being 30 days while it was discontinued indefinitely due to infection in 3 patients. Previous fludarabine therapy (p = 0.024) was the only factor associated with the occurrence of infection unlike previous number of therapy, neutropenia, leukopenia and levels of immunoglobulin G. In survival analysis, infections in general were not associated with poorer outcome (p = 0.265), but the grade of infection was associated with poorer outcome (p = 0.003) Summary/Conclusion: Our findings show, however, higher grade of serious infections than pivotal RESONATE trial with expected incidence early in the treatment course. The role of temporary ibrutinib withdrawal due to an infection should be explored in the greater samples possible through the larger observational studies.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA