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Elderly chronic lymphocytic leukaemia (CLL) patients treated outside of trials have notably greater toxicity with the Brutons tyrosine kinase inhibitor ibrutinib compared to younger patients. It is not known whether the same holds true for the B-cell lymphoma 2 inhibitor venetoclax. We provide a comprehensive analysis of key safety measures and efficacy in 342 patients comparing age categories ≥75 and

This document is a guideline published in the British Journal of Haematology that provides healthcare professionals with clear guidance on the diagnosis and management of patients with marginal zone lymphoma (MZL). MZL is a group of clinically indolent mature B-cell lymphomas that arise from memory B cells in the marginal zones of secondary lymphoid tissues. The guideline discusses the different subtypes of MZL, diagnostic methods, and potential aetiological factors. It also includes information on treatment options for different stages of MZL, including radiotherapy, systemic therapy, and targeted agents. The document emphasizes the importance of individualized patient care and shared decision making. [Extracted from the article]

RT occurs in 2-10% of CLL patients, usually during the disease course rather than at presentation, representing a transformation rate of 0-5-1% per CLL patient per year.2-5 RT should be suspected when a CLL patient develops one or more new "B symptoms", asymmetric, rapidly progressive lymphadenopathy, or a sudden lactate dehydrogenase (LDH) rise. Treatment approach Patients with RT commonly present in the context of pre-treated CLL and immunosuppression, and given the typical demographics of the CLL population, patients are often older with co-existing comorbidities.22 Treatment has historically involved multi-agent cytotoxic chemotherapy, more recently in combination with an anti-CD20 monoclonal antibody. Patients with I TP53 i aberrations or those who develop RT having previously received CLL-directed treatment have a poor outcome with R-CHOP alone, although this remains the standard of care and provides at least initial disease control for most patients. Diffuse large B-cell lymphoma (Richter syndrome) in patients with chronic lymphocytic leukaemia (CLL): a cohort study of newly diagnosed patients. [Extracted from the article]

If AF rate control is not possible pharmacologically, then atrioventricular node (AVN) ablation and cardiac resynchronisation therapy (CRT) pacemaker implantation may be considered for symptomatic fast AF when CLL-related prognosis is more than one year.66,67 Recent studies have shown that the leading cause of death for AF patients already treated with appropriate anticoagulation is heart failure. Second, there are multiple drug interactions between ibrutinib and antiarrhythmic agents used for rate and rhythm control (amiodarone, digoxin, verapamil and diltiazem) via CYP3A4 hepatic metabolism.63-65 Atrial fibrillation ablation targeting the pulmonary veins is not recommended as it rarely offers long term AF-free survival. Keywords: ibrutinib; bruton tyrosine kinase inhibitor; atrial fibrillation; hypertension; sudden cardiac death; cardiovascular complication EN ibrutinib bruton tyrosine kinase inhibitor atrial fibrillation hypertension sudden cardiac death cardiovascular complication 70 78 9 12/27/21 20220101 NES 220101 Methodology This Good Practice Paper was compiled according to the British Society for Haematology (BSH) process at BSH Guidelines Development Process (PDF). GRAPH Footnotes 1 A recent alert from an unpublished clinical trial (FLAIR: a phase III, randomised controlled trial comparing the use of ibrutinib and rituximab [IR] versus FCR versus ibrutinib and venetoclax in treatment naïve CLL patients) reported that patients in the ibrutinib and rituximab (IR) arm have an elevated risk of sudden cardiac death if they were on ACE inhibitor treatment at study entry versus patients not on ACE inhibitors at study entry. [Extracted from the article]

The article discusses a study on the temporal TP53 gene variation in patients with Waldenström Macroglobulinaemia (WM). Topics covered include a 29% detection and development of TP53 variation in patients, the need to test TP53 genes at presentation and prior to therapy, and such pertinent genes involved in WM as MYD88, CXCR4, and BTK. Also noted is the possible use of liquid biopsies to monitor patients for TP53 variation.

Summary: Venetoclax is a BCL2 inhibitor with activity in relapsed/refractory (R/R) chronic lymphocytic leukaemia (CLL). We conducted a multi‐centre retrospective analysis of 105 R/R CLL patients who received venetoclax pre‐National Health Service commissioning. The median age was 67 years and median prior lines was 3 (range: 1–15). 48% had TP53 disruption. At ≥2 lines, 60% received a Bruton Tyrosine Kinase inhibitor (BTKi) and no prior phosphoinositide 3‐kinase inhibitor (Pi3Ki), 25% received a Pi3Ki and no prior BTKi, and 10% received both. Patients discontinued B cell receptor inhibitor (BCRi) because of toxicity in 44% and progression in 54%. Tumour lysis syndrome risk was low, intermediate or high in 27%, 25%, and 48% respectively. Overall response was 88% (30% complete response [CR]). The overall response rate was 85% (CR 23%) in BTKi‐exposed patients, 92% (CR 38%) in Pi3Ki‐exposed patients and 80% (CR 20%) in both (P = 0·59). With a median follow‐up of 15·6 months, 1‐year progression‐free survival was 65·0% and 1‐year overall survival was 75·1%. Dose reduction or temporary interruption did not result in an inferior progression‐free or discontinuation‐free survival. Risk of progression or death after stopping a prior BCRi for progression was double compared to those stopping for other reasons (predominantly toxicity) (Hazard Ratio 2·01 P = 0·05). Venetoclax is active and well tolerated in R/R CLL post ≥1 BCRi. Reason(s) for stopping BCRi influences venetoclax outcomes. [ABSTRACT FROM AUTHOR]

The article discusses a study that examined the clinical relevance of two biomarkers, DNA methylation epitype (DME) and telomere length (TL), in chronic lymphocytic leukemia (CLL) patients. The study found that both DME and TL can provide independent prognostic information, with patients having shorter telomeres and specific DME subgroups experiencing poorer outcomes. These findings suggest that DME and TL could be valuable biomarkers for risk stratification in CLL patients. However, as a letter to the editor of a scientific journal, this document does not provide specific information or content that can be summarized for library patrons conducting research on specific topics. [Extracted from the article]