infections

Infections in Chronic Lymphocytic Leukemia Patients Treated with Ibrutinib: Incidence and Predisposing Factors

ANTINEOPLASTIC THERAPY COMPLICATIONS ,

EA Dmitrieva1, EA Nikitin1, EE Markova1, NYu Dmitrieva2, VV Ptushkin1

1 SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284

2 Aston Consulting, 10 bld. 3 Shabolovka str., Moscow, Russian Federation, 119049

For correspondence: Evgenii Aleksandrovich Nikitin, MD, PhD, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284; Tel.: +7(916)572-06-44; e-mail: eugene_nikitin@mail.ru

For citation: Dmitrieva EA, Nikitin EA, Markova EE, et al. Infections in Chronic Lymphocytic Leukemia Patients Treated with Ibrutinib: Incidence and Predisposing Factors. Clinical oncohematology. 2019;12(4):438–48 (In Russ).

DOI: 10.21320/2500-2139-2019-12-4-438-448

ABSTRACT

Background. Infections are a common complication of chronic lymphocytic leukemia (CLL). The lack of recommendations for infection prevention in CLL patients treated with ibrutinib can be attributed by an insufficiency of data in the literature.

Aim. To assess the incidence and nature of infections in CLL patients treated with ibrutinib and to analyze predisposing factors.

Materials & Methods. The paper provides data on bacterial, viral, and fungal infections in CLL patients treated with ibrutinib for 4.2 years (November 2014 to December 2018) in a single center. Severity grade was determined according to CTCAE criteria (version 4).

Results. The trial included 240 CLL patients. Median age was 65 years (range 32–91), 86 (36 %) patients were female, and 117 (48 %) patients had Binet stage C. Ibrutinib as monotherapy was administered to 204 (85 %) patients, 36 (15 %) patients received it in combination with monoclonal anti-CD20 antibodies. Median follow-up was 14.8 months (range 1–54). Most patients (n = 224, 93 %) received ibrutinib for relapsed CLL. Median number of prior therapy lines was 3 (range 1–12). Neutropenia (specified as neutrophil level < 1000 cells/µL) before ibrutinib treatment was identified in 20 (8 %) patients. Glucocorticoid hormones (GCs) together with ibrutinib were administered to 20 patients. A total of 525 infectious episodes were registered in 183 patients. Out of them 381 (72.5 %) were bacterial/mixed, 115 (22 %) were viral, and 29 (5.5 %) were fungal infections. Among bacterial/mixed infections 121 (32 %) episodes were qualified as infection of grade 3 and 43 (11 %) episodes were qualified as grade 4. In 7 (1.8 %) patients infections were fatal. Within 12 months overall cumulative incidence of bacterial infections of grade 3/4 was 37 % (95% confidence interval [95% CI] 31–43 %), as for viral infections it was 28 % (95% CI 22–34 %), and as for fungal infections it was 8 % (95% CI 4–12 %). Higher cumulative incidence of bacterial infections of grade 3/4 was identified in patients with ≥ 3 lines of therapy before ibrutinib treatment (hazard ratio [HR] 2.0; 95% CI 1.36–2.97), with Binet stage C (HR 1.4; 95% CI 0.95–2.08), with ECOG status ≥ 2 (HR 2.4; 95% CI 1.6–3.6), baseline neutropenia (HR 1.25; 95% CI 0.73–2.13), as well as in men (HR 1.8; 95% CI 1.16–2.8; p = 0.004). Multivariate analysis showed that male sex (HR 1.89; 95% CI 0.5–3.0; p = 0.006), ECOG status ≥ 2 (HR 1.97; 95% CI 0.5–3.0), and baseline neutropenia (HR 1.76; 95% CI 0.99–3.1) were significant and independent risk factors. Cumulative incidence of any fungal infection was associated with simultaneous use of GCs (HR 6.0; 95% CI 5.85–14.7) and baseline neutropenia (HR 2.36; 95% CI 0.95–5.85). The only parameter significantly associated with viral infections was the number of prior therapy lines ≥ 3 (HR 1.74; 95% CI 1.06–2.86; p = 0.029).

Conclusion. Patients with baseline neutropenia and ECOG status ≥ 2 face the highest risk of severe bacterial infections. We believe that antibacterial prophylaxis should be considered in such patients till ECOG status becomes < 2 and neutropenia resolves. Patients receiving GCs together with ibrutinib face the risk of fungal infections at any stage of treatment. In these patients the simultaneous antifungal prophylaxis should be considered.

Keywords: chronic lymphocytic leukemia, infections, ibrutinib.

Received: March 27, 2019

Accepted: September 19, 2019

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Taxonomic Structure and Antibiotic Resistance of Bloodstream Infection Pathogens in Oncohematological Patients

INFECTIONS IN ONCOHEMATOLOGY , , , , , ,

NS Bagirova

N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Natal’ya Sergeevna Bagirova, DSci, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-18-60; e-mail: nbagirova@mail.ru

For citation: Bagirova NS. Taxonomic Structure and Antibiotic Resistance of Bloodstream Infection Pathogens in Oncohematological Patients. Clinical oncohematology. 2015;8(2):191–200 (In Russ).

ABSTRACT

Background & Aims. In oncohematology, infections are one of main causes of morbidity and mortality in patients with hematological malignancies. Changing epidemiological patterns of infections in patients with hematological malignancies are characterized not only by the appearance of new pathogens of bloodstream infections, but also by the growth of pathogens resistant to antimicrobial drugs. It is important to conduct constant monitoring of taxonomic structure of bloodstream infections pathogens and their antimicrobial resistance in order to ensure adequate and timely treatment of severe infections. The aim of the study is the following: analysis of the taxonomic structure of pathogens isolated while diagnosing bacteremia in adult cancer patients using modern devices taking into account efficacy of the therapy of severe infections.

Methods. A microbiological study of blood samples of adult patients with hematological malignancies was carried out over the period from 2005 till 2013, if sepsis and other severe infections were suspected. Bacteremia was diagnosed using hematological analyzer/incubator Bactec FX400 (Becton Dickinson, USA) and Bact/Alert (BioMerieux, France), identification of strains was done using mass-spectrometer MALDI-TOF Microflex LT (Biotyper, Bruker Daltonics, Germany). Antimicrobial susceptibility was determined using automatic analyzers Microscan Walk Away 40/96+ (Siemens, Germany) and Vitek 2 (BioMerieux, France). Comparative data of foreign researchers are presented.

Results. 3794 blood cultures were obtained, 600 of which (15.8 %) demonstrated growth. Of 392 strains, only 210 (53.6 %) strains were considered true causative agents of bacteremia. No statistically significant differences in the frequency of isolation of Gram-positive cocci (47.6 %) and Gram-negative rods (39.5 %) were found. Fungi were significantly less common than Gram-positive cocci and Gram-negative rods (9 %; p < 0.0001). Other microorganisms constituted 3.8 %.

Conclusion. Therapy and prevention of infectious complications in adult patients with hematological malignancies are accompanied by development of growing antibiotic resistance of pathogens. Changes in taxonomic structure of pathogens of bloodstream infections should be taken into account when prescribing the empirical and etiotropic treatment.

Keywords: infections, cancer, bloodstream infections, bacteriemia, antimicrobial resistance, oncohematological disorders, antimicrobial therapy.

Received: January 12, 2015

Accepted: January 30, 2015

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