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Simple Summary: In clinical trials, ibrutinib was found to be effective and well-tolerated in patients with chronic lymphocytic leukemia (CLL). To confirm these findings, data on unselected patients treated in clinical practice are necessary. The aim of our observational, prospective Italian cohort study was to describe the real-world persistence rate, patterns of use, and clinical outcomes in patients with CLL treated with single-agent ibrutinib across various treatment lines. We found that, despite the high burden of patient comorbidities and unfavorable genetic features, the majority of patients (217/309, 70%), especially those treated in first line (75%), continued ibrutinib treatment for ≥2 years. The most common reasons for treatment discontinuation were adverse events, primarily infections. We reported positive clinical and survival outcomes, especially in the first-line cohort, and a safety profile consistent with clinical trial data. Our data suggest that ibrutinib is a valuable option for both treatment-naïve and previously treated patients with CLL. Real-world data in clinical practice are needed to confirm the efficacy and safety that ibrutinib has demonstrated in clinical trials of patients with chronic lymphocytic leukemia (CLL). We described the real-world persistence rate, patterns of use, and clinical outcomes in 309 patients with CLL receiving single-agent ibrutinib in first line (1L, n = 118), 2L (n = 127) and ≥3L (n = 64) in the prospective, real-world, Italian EVIdeNCE study. After a median follow-up of 23.9 months, 29.8% of patients discontinued ibrutinib (1L: 24.6%, 2L: 29.9%, ≥3L: 39.1%), mainly owing to adverse events (AEs)/toxicity (14.2%). The most common AEs leading to discontinuation were infections (1L, ≥3L) and cardiac events (2L). The 2-year retention rate was 70.2% in the whole cohort (1L: 75.4%, 2L: 70.1%, ≥3L: 60.9%). The 2-year PFS and OS were, respectively, 85.4% and 91.7% in 1L, 80.0% and 86.2% in 2L, and 70.1% and 80.0% in ≥3L. Cardiovascular conditions did not impact patients' clinical outcomes. The most common AEs were infections (30.7%), bleeding (12.9%), fatigue (10.0%), and neutropenia (9.7%), while grade 3–4 atrial fibrillation occurred in 3.9% of patients. No new safety signals were detected. These results strongly support ibrutinib as a valuable treatment option for CLL. [ABSTRACT FROM AUTHOR]

Competing Interests: Paolo Ghia received honoraria from AbbVie, AstraZeneca, BeiGene, BMS, Galapagos, Janssen, Lilly/LoxoOncology, MSD, and Roche, and research funding from AbbVie, AstraZeneca, BMS, and Janssen, and is an Editor of HemaSphere. Marzia Varettoni received honoraria from AbbVie, AstraZeneca, BeiGene, and Janssen. The remaining authors declare no conflict of interest.

Ibrutinib, a highly effective inhibitor of the Bruton tyrosine kinase, has significantly transformed the therapeutic approach in chronic lymphocytic leukemia (CLL). Despite these advancements, the disease continues to be characterized by immune dysfunction and increased susceptibility to infections, with mortality rates from infections showing no significant improvement over the past few decades. Therefore, timely prevention, recognition, and treatment of infections remains an important aspect of the standard management of a patient with CLL. A panel of hematologists with expertise in CLL met to discuss existing literature and clinical insights for the management of infectious in CLL undergoing ibrutinib treatment. Despite not being a fully comprehensive review on the topic, this work provides a set of practical recommendations that can serve as a guide to healthcare professionals who manage these patients in their daily clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Baratè, Scortechini, Ciofini, Picardi, Angeletti, Loscocco, Sanna, Isidori and Sportoletti.)

A panel of chronic lymphocytic leukemia (CLL) experts from Tuscany propose a real-life diagnostic and therapeutic approach CLL that considers the role of genomic and somatic prognostic factors in risk stratification and treatment decisions. Safety and efficacy of new agents has been demonstrated now not only in clinical trials but also in many real-world series. The BTK inhibitors, ibrutinib and acalabrutinib, and BH3 mimetic venetoclax are now indicated as first-line therapy and chemoimmunotherapy can be spared to the majority of CLL patients, thus preventing unnecessary hematological and non-hematological toxicity and second primary tumors. For treatment, FISH for 17 p and P53 mutational status are essential. IGHV mutation can be done at diagnosis or before treatment. Echography is the gold standard radiological investigation in CLL, at both diagnosis and response evaluation. Chemotherapy is virtually abandoned. Age, genetic risk, and patient comorbidities have to be carefully evaluated for treatment decision. With the availability of different drugs, there is a need for a uniform and shared approach in daily therapeutic choice. The proposed approach is based on current evidence and guidelines as well as results from clinical trials and daily clinical experience., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The identification of mature T cell neoplasms by flow cytometry is often challenging, due to overlapping features with reactive T cells and limitations of currently available T cell clonality assays. The description of an antibody specific for one of two mutually exclusive T cell receptor (TCR) β-chain constant regions (TRBC1) provides an opportunity to facilitate the detection of clonal TCRαβ+ T cells based on TRBC-restriction. Here we prospectively analyzed 14 healthy controls and 63 patients with the flow cytometry protocol currently used for suspected T cell neoplasm implemented with immunostaining targeting TRBC1. Specimens were firstly classified in 3 groups based on clinical records data, laboratory findings and immunophenotypic features. T cell clonality was assessed by TCR Vβ repertoire analysis and the new rapid TRBC1 assay. Results showed that TRBC1 unimodal expression was unequivocally associated with samples presenting with immunophenotypic aberrancies. Moreover, we demonstrated that the use of TRBC1 is useful in solving uncertain cases and confirmed the high sensitivity of the method in identifying small T cell clones of uncertain significance (T-CUS). Finally, we found a high degree of concordance (97%) comparing the currently available clonality assessment methods with the proposed new method. In conclusion, our results provided real-life evidence of the utility of TRBC1 introduction in the flow cytometric clonality evaluation for the routine diagnostic work-up of T cell neoplasms., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)