Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries, accounting for approximately 30% of all leukemias. Infections are the major cause of morbidity and mortality of CLL patients and represent the clinical effects of a multi-factorial immunodeficiency related to the underlying disease, treatment and the older age of patients.
Severe infections, were reported in 12.8-26% of treatment naive (TN) and relapsed/ refractory (R/R) patients treated with the bendamustine and rituximab (BR) chemoimmunotherapy in controlled trials (CT). Kinase inhibitors (KIs) of the B-cell receptor (BCR) patway have allowed remarkable improvements in the outcome of CLL patients. These agents will be soon considered as the preferable option for the treatment of a large proportion of patients, including elderly and unfit patients.
However, infections still represent an important cause of morbidity also in patients treated with the KIs ibrutinib or idelalisib. In a CT 27% of R/R patients developed a severe infection while on ibrutinib treatment. Infections, are common also in patients treated with idelalisib. In CTs including R/R patients treated with idelalisib combined with rituximab severe infections were described in 29% of the cases.
Little is known about the infection rate and factors associated with an increased risk of infections in R/R patients with CLL treated with BR or KIs inhibitors in the real world.
The purpose of this multicenter, retrospective study that will include a large series of patients with CLL, is to define the proportion of unselected patients treated in the real world who develop a severe infection after treatment with BR or KIs. In addition, we will investigate factors associated with an increased risk of infections. The results of this study could be of help in the decision-making process to address the optimal treatment choice and the adequate infection prophylaxis in CLL patients.
CLL is the most frequent leukemia in adult population with a median age at onset of about 70 years. The overall prevalence in Italy is of 49 cases /100.000subjects of all ages and of 207cases/100.000 subjects when subjects of age of 75 years or older are considered.
As life expectancy is increasing, many countries are experiencing an increase in older individuals and by the year 2030 people over 65-70 years are expected to account for more than 70% of all patients with cancer. On this basis, an increase in the number of patients with a CLL diagnosis is expected.
The immunosenescence, the state of dysregulated immune function associated with CLL, older age and treatments play an important contributory role towards the risk of infections.
In recent years, innovative drugs have enriched the therapeutic armamentarium for patients with chronic lymphocytic leukemia (CLL) and are widely used in the clinical practice. These small molecules targeting the B-cell receptor signaling pathway protein offer new chemo-free options to both unfit patients and high-risk patients who show a poor response to chemoimmunotherapy. Nonetheless, data from recent controlled CTs show that severe infections are a frequently observed also in CLL patients treated with a chemo-free treatment approach including the BCR antagonist ibrutinib and idelalisib.
Limited information is available about the proportion of unselected patients with CLL treated in clinical practice who develop infections after advanced line chemoimmunotherapy or KIs given in clinical practice.
In addition, little is known about factors associated with an increased risk of infections. The identification of factors associated with an increased risk of infections in patients treated with chemoimmunotherapy or KIs, could be of help in the decision-making process of the treatment choice and could address measures of infection prevention in patients with CLL.