Kinetics of lymphocytosis in naïve chronic lymphocytic leukemia patients treated with covalent Bruton's tyrosine kinase inhibitors: An Italian multicenter real‐life experience

作者：Idanna Innocenti, Antonio Mosca, Annamaria Tomasso, Andrea Galitzia, Lydia Scarfò, Francesca Morelli, Eugenio Galli, Francesca Martini, Eugenio Sangiorgi, Roberta Laureana, Giulia Benintende, Veronica Mattiello, Sabrina Chiriu, Maria Ilaria Del Principe, Giulia Zamprogna, Massimo Gentile, Enrica Antonia Martino, Emilia Cappello, Maria Chiara Montalbano, Giuliana Farina, Vanessa Innao, Luca Stirparo, Caterina Patti, Paolo Sportoletti, Alberto Fresa, Gioacchino Catania, Marta Coscia, Silvia Bellesi, Alessandra Tedeschi, Alessandro Sanna, Andrea Visentin, Francesco Autore, Raffaella Pasquale, Livio Trentin, Marzia Varettoni, Paolo Ghia, Roberta Murru, Luca Laurenti · 发表于：HemaSphere · 年份：2024 · DOI：10.1002/hem3.144 · 被引用次数：4 · 研究领域：Chronic Lymphocytic Leukemia Research、Chronic Myeloid Leukemia Treatments、Lymphoma Diagnosis and Treatment

Chronic lymphocytic leukemia (CLL) therapy has recently undergone a revolution with the introduction of a new class of drugs: covalent Bruton's tyrosine kinase inhibitors (cBTKi), paving the way for a chemotherapy-free approach.1-4 Presently, cBTKi can be utilized in the first line of CLL management, thanks to the results of phase III clinical trials such as RESONATE-2 and ELEVATE-TN, which demonstrated the superiority of Ibrutinib over chemotherapy with chlorambucil5 and acalabrutinib over chemoimmunotherapy with chlorambucil + obinutuzumab,6 in terms of progression-free survival (PFS) in both cases. Ibrutinib exhibited better PFS, overall survival (OS), and overall response rate than the monoclonal anti-CD20 antibody ofatumumab in previously treated patients with CLL.7 Additionally, the ASCEND study, another phase III randomized clinical trial, demonstrated that acalabrutinib significantly improved PFS compared to a physician's choice of Idelalisib + rituximab or bendamustine + rituximab, in patients with relapsed/refractory CLL.8 BTK plays a pivotal role in B-cell receptor (BCR) signal transduction,9 stimulating important pathways such as NFKB10, 11 and CXCR4.12 Consequently, BTK is involved in B-cell survival, proliferation, and adhesion, while its activation promotes B-cell proliferation.13 Paradoxically, ibrutinib has shown to increase absolute lymphocyte count (ALC) in the initial phase of treatment, regardless of previous lines of therapy. Ibrutinib-induced lymphocyto...