Real-World Treatment Patterns After Discontinuation of Venetoclax or BTKis in the Frontline Setting Among Older Adults With Chronic Lymphocytic Leukemia.

Purpose: Venetoclax and Bruton's tyrosine kinase inhibitors (BTKis) are key treatment options for patients with chronic lymphocytic leukemia (CLL) in the frontline setting. This study characterized postdiscontinuation treatment patterns and hospitalization of frontline venetoclax and BTKis in a national sample of older adults with CLL.

Methods: We identified 1,770 Medicare beneficiaries 66 years and older with CLL initiating venetoclax with obinutuzumab (VEN-O, n = 193) or BTKi treatment (n = 1,577) in the frontline setting between June 01, 2019, and June 30, 2020.

Racial disparities in chronic lymphocytic leukemia/small lymphocytic lymphoma accounting for small molecule inhibitors: A real-world cohort analysis.

Kaplan-Meier curve depicting overall survival from CLL treatment start by race. For patients with CLL, no overall survival difference was observed between races in this real-world US database.

Kinase-impaired BTK mutations are susceptible to clinical-stage BTK and IKZF1/3 degrader NX-2127.

Increasing use of covalent and noncovalent inhibitors of Bruton's tyrosine kinase (BTK) has elucidated a series of acquired drug-resistant BTK mutations in patients with B cell malignancies. Here we identify inhibitor resistance mutations in BTK with distinct enzymatic activities, including some that impair BTK enzymatic activity while imparting novel protein-protein interactions that sustain B cell receptor (BCR) signaling. Furthermore, we describe a clinical-stage BTK and IKZF1/3 degrader, NX-2127, that can bind and proteasomally degrade each mutant BTK proteoform, resulting in potent blockade of BCR signaling.

MRD-directed therapy in CLL: ready for prime time?

In recent years, the treatment paradigm for patients with chronic lymphocytic leukemia (CLL) has moved away from chemoimmunotherapy (CIT) toward the use of novel targeted agents. Commercially available drugs, including Bruton's tyrosine kinase inhibitors and the BCL2 inhibitor venetoclax, often used in combination with anti-CD20 monoclonal antibodies, are now the mainstay of therapy both in the frontline and in relapsed settings. As the landscape for CLL management evolves, therapeutic endpoints need to be redefined.

Results from a Real-World Multicenter Analysis of 482 Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib: A Look at Racial Differences.

Background: Despite recent approvals of lifesaving treatments for chronic lymphocytic leukemia (CLL), real-world data on the tolerability of the Bruton tyrosine kinase inhibitor ibrutinib for CLL treatment are lacking, especially in Black patients.

Objective: To expand upon a previously reported retrospective chart review of ibrutinib-treated patients with CLL to increase the number of sites and the enrollment period in first-line (1L) and relapsed/refractory (R/R) settings with a subanalysis based on ethnicity.

Patients And Methods: Adults with CLL who initiated ibrutinib treatment from five centers were followed for ≥ 6 months.

Combining Super Learner with high-dimensional propensity score to improve confounding adjustment: A real-world application in chronic lymphocytic leukemia.

Purpose: High-dimensional propensity score (hdPS) is a semiautomated method that leverages a vast number of covariates available in healthcare databases to improve confounding adjustment. A novel combined Super Learner (SL)-hdPS approach was proposed to assist with selecting the number of covariates for propensity score inclusion, and was found in plasmode simulation studies to improve bias reduction and precision compared to hdPS alone. However, the approach has not been examined in the applied setting.

How Have Targeted Agents Changed the Treatment Landscape for Elderly Patients with CLL?

Purpose Of Review: Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy in elderly patients. At the time of diagnosis, most patients have comorbid medical conditions. Although patients have other competing medical issues, the majority of patients will die from CLL or CLL-related complications.

Vaccination efficacy in patients with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a disorder of mature malignant B cells with multiple elements of immune dysfunction. Infections are common in CLL patients due to complex immunodeficiency. Vaccines are used as preventative measures for common diseases including influenza, pneumococcus, tetanus/diphtheria and shingles in the general population.

Zanubrutinib (BGB-3111), a Second-Generation Selective Covalent Inhibitor of Bruton's Tyrosine Kinase and Its Utility in Treating Chronic Lymphocytic Leukemia.

The understanding of the B cell receptor (BCR) pathway and its contribution to chronic lymphocytic leukemia (CLL) pathogenesis have led to the development of targeted BCR inhibitors which have transformed the treatment paradigm of CLL. Ibrutinib is a first-in-class oral Bruton's tyrosine kinase (BTK) inhibitor which has demonstrated improvements in both progression free (PFS) and overall survival (OS) in both the treatment naïve and relapsed/refractory setting as compared to traditional chemoimmunotherapy. Despite its clinical efficacy, many patients discontinue treatment due to adverse events, which are thought to be mediated through off-target kinase inhibition.

Chemotherapy-free frontline therapy for CLL: is it worth it?

The treatment of chronic lymphocytic leukemia (CLL) embodies one of the great success stories in translational research, with the development of therapies aimed at disrupting crucial pathways that allow for the survival and proliferation of the malignant clone. The arrival of targeted agents into our armamentarium, along with the advent of novel monoclonal antibodies that can achieve deeper remissions, has steered the field to a new treatment paradigm. Given the panoply of therapeutic options available, the question arises whether chemotherapy still has a role in the management of CLL.

Ibrutinib-associated Arthralgias/Myalgias in Patients With Chronic Lymphocytic Leukemia: Incidence and Impact on Clinical Outcomes.

Introduction: The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has transformed the treatment of chronic lymphocytic leukemia (CLL), leading to unprecedented improvements in progression-free and overall survival for all patients, including those with poor prognostic features. The side effect profile of ibrutinib is unique compared with chemoimmunotherapy and includes atrial fibrillation, increased bleeding risk, and arthralgias/myalgias. Although common, arthralgias/myalgias and their management are poorly described.

Chimeric Antigen Receptor T Cells in Chronic Lymphocytic Leukemia: Are We Any Closer to a Cure?

Recent advances in the treatment of chronic lymphocytic leukemia (CLL) have dramatically changed outcomes for patients. Despite these improvements, CLL is still considered incurable. Chimeric antigen receptor-modified T cells have demonstrated the ability to produce long-term remissions in subsets of heavily pretreated patients with B-cell malignancies, including CLL.

Management of giant cell hepatitis associated with chronic lymphocytic leukemia - a case series and review of the literature.

Giant cell hepatitis (GCH) is a rare diagnosis in adults that is found in 0.25% of liver biopsies. GCH has been associated with multiple causes including drugs (6-mercaptopurine, methotrexate), toxins, viruses and autoimmune.

PET/Computed Tomography in Chronic Lymphocytic Leukemia and Richter Transformation.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the United States. In 1-10% of cases, it can undergo Richter's transformation (RT) to either diffuse large B cell lymphoma (DLBCL) or Hodgkin's lymphoma (HL). Diagnosis requires histologic confirmation by tissue biopsy.