Analysis of the risk of infection in patients with chronic lymphocytic leukemia in the era of novel therapies

Abstract

We studied the risk of infections in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). Major infections were defined as requiring hospital admission or intravenous antimicrobial treatment. Incidence rate (IR) ratios (IRR) were used to compare infection rates. Of 263 CLL patients followed for 936.9 person-years, 60% required treatment for progressive CLL (66 received ibrutinib). Infections occurred in 71.9% patients (IR 92.4/100 person-years) with 31.9% having major infections (IR 20.3/100 person-years) and infections causing 37.5% of deaths. CLL treatment was associated with significantly higher risk of major (IRR 3.31, 95% CI 2.10, 5.21) and minor (IRR 1.78, 95% CI 1.43, 2.22) infections. Compared to their previous chemoimmunotherapy patients receiving salvage ibrutinib therapy (n = 47) had a significantly increased risk of a major infection (IRR 2.35 95% CI 1.27, 4.34). The risk of infection in CLL patients remains high even with use of less immunosuppressive therapies.

Long-Term Ibrutinib Therapy Reverses CD8+ T Cell Exhaustion in B Cell Chronic Lymphocytic Leukaemia

“…Ibrutinib has previously been associated with improvements in T cell function including an increase the degree of diversity within the T cell repertoire (14) and enhanced outcome of CAR-T therapy in patients with CLL (20). Our findings now demonstrate a reversal in the degree of phenotypic and functional exhaustion and help to explain the encouraging clinical experience of BTKi therapy in relation to infection risk (21).…”

Diagnosis and management of complications of chronic lymphocytic leukemia/small lymphocytic lymphoma

“…The risk and consequences of infections in CLL patients could also be changing because of the increasing use of less toxic and more effective targeted therapy [28] that have decreased the rate of serious infections following initiation of therapy [29]. reported at rate of 3.1/100 patient-years with most (90%) being considered minor infections (grade <3) but with the potential to cause serious long-term neuropathy [3]. Disseminated varicella zoster is a rare but serious complication of CLL and its treatment [31].…”

“…CLL patients are at increased risk of paraneoplastic pemphigus [44], glomerulonephritis [63], and angioedema caused by C1q inhibitor deficiency [64]. CLL patients also have an increased risk of exaggerated arthropod reactions especially after mosquito bites that can lead to loss of skin integrity and serious skin infections [3,44].…”

“…Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is the most prevalent lymphoid malignancy in Europe [1] and North America [2] and causes considerable morbidity and mortality. CLL is associated with early onset and often profound immune dysregulation that increases the risk of infection, second malignancies, and autoimmune complications [3][4][5]. The incidence and prevalence of these complications are likely to increase because of population aging and the ongoing development of more effective but still noncurative therapies resulting in longer survival.…”

Infection with ibrutinib in patients with chronic lymphocytic leukemia: How strong is the association?

“…Based on our clinical experience and the results of ibrutinib trials, we agree with the authors regarding the possibility of increased risk of infections with ibrutinib. 2,3 However, chronic lymphocytic leukemia (CLL) and other B-cell malignancies by themselves confer increased risk of infections owing to acquired defects of the innate and adaptive immunity secondary to the disease process, hypogammaglobulinemia, and T-cell and complement dysfunction, among others. 4,5 The authors have succinctly summarized the rate and types of infections in the ibrutinib arms of the trials.…”