IGH (Immunoglobulin Heavy Locus)

Standard frontline treatment of chronic lymphocytic leukemia (CLL) is with fixed-duration venetoclax-based doublets or indefinite covalent Bruton tyrosine kinase inhibitor (BTKI)...We recommend considering triplets in treatment naïve CLL patients with IGHV-U, TP53 wild type, anticipated low incidence/good tolerance of Gr ≥ 3 infection (<70 years old, no major comorbidity and fully immunized) who are well informed and prioritize maximal time off therapy at the expense of increased short-term logistical complexity. Future triplet research should focus on randomized trials in specific genomic subgroups, incorporating novel agents (e.g., non-covalent BTKI, BTK degrader, and next-generation BCL2 inhibitors) and new ways of adapting treatment duration to maximize efficacy and minimize toxicity.

This offers a focused site for blockade. IGHV4-34 is a paradigm of the plasticity of B cells, of interaction with potential autoantigens, and of their subversion in tumors.

Undetectable minimal residual disease (uMRD) has emerged as a critical prognostic and potentially predictive biomarker in chronic lymphocytic leukemia (CLL), particularly in venetoclax-based time-limited regimens...Ongoing trials will further define the role of MRD-adapted therapy duration in first-line CLL treatment. Overall, MRD is a powerful tool to move beyond one-size-fits-all regimens and may become integral in personalizing CLL management across diverse therapeutic regimens.

Venetoclax combination regimen achieved excellent efficacy and safety in the treatment of relapsed/refractory multiple myeloma with t(11;14) in this case. The treatment of patients with relapsed and refractory multiple myeloma with t(11;14) by venetoclax still needs to be confirmed by more clinical studies.

The cumulative burden of high-risk cytogenetic abnormalities predicts inferior survival in NDMM, underscoring the need for refined risk stratification and tailored therapeutic strategies.

Notably, NGS and digital droplet PCR confirmed a TP53 frameshift mutation (c.902del; p.Pro301Glnfs*44) with a fractional abundance of 0.31% in the lymph node and a (c.742C>T; p.Arg248Trp) mutation (0.309%) in the bone marrow. Results underscore the importance of NGS-based clonality to diagnose NMZL with prominent PD1+ T-cell hyperplasia, and prompt further investigation into tissue-specific mutational signatures in these unusual cases.

The primary first-line treatment options for CLL comprise continuous therapies based on the BTK inhibitors ibrutinib, zanubrutinib, or acalabrutinib, or fixed-duration regimens combining the BCL2 inhibitor venetoclax with obinutuzumab or the BTK inhibitors ibrutinib or acalabrutinib (with or without obinutuzumab). Selecting the appropriate targeted therapy requires careful evaluation of a multitude of factors, including molecular disease features (especially del&lsqb;17p]/TP53 and IGHV mutational status), comorbidities, comedications, and the patient's preferences. Focusing on primary treatment options, we review data from the key controlled trials that support the first-line use of targeted therapies for patients with CLL, consider ongoing trials that may support clinical decision-making in the future, and assess the potential to personalize treatment regimens in CLL based on minimal residual disease status.

We compared an MRD-guided, fixed-duration ibrutinib-venetoclax (IV) regimen to fludarabine-cyclophosphamide-rituximab (FCR) in this population. A patient profile suitable for an MRD-guided, fixed-duration IV regimen requires consideration of potential toxicities. Abbvie and Janssen France.

Future studies should explore long-term durability beyond 5 years and validate MRD thresholds for treatment cessation. National Nature Science Foundation of China, the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and Beijing Xisike Clinical Oncology Research Foundation.

This case illustrates a fulminant presentation of primary vitreoretinal lymphoma, characterized by rapidly progressive optic disc involvement and extensive serous retinal detachment. Despite the severity, early diagnostic vitrectomy followed by prompt intravitreal methotrexate enabled anatomical and functional recovery.

The cBTKi + V regimen is easy to manage and relatively well tolerated. However, cBTKi-related cardiovascular toxicities remain a limiting concern, especially for the use of cBTKi + V in some older patients.

Combining ibrutinib with the GPX4 inhibitor RSL3 enhances ferroptosis and improves antileukemic efficacy in vivo. Notably, ACSL1 is selectively upregulated in U-CLL cells and represents a targetable metabolic enhancer of ferroptosis sensitivity, as shown in vivo. Our findings reveal that TFRC and ACSL1 are functionally distinct yet targetable nodes that govern ferroptosis vulnerability in CLL patients and may guide novel therapeutic strategies for high-risk patients.