Risk-stratification in frontline CLL therapy: standard of care.

The treatment of chronic lymphocytic leukemia (CLL) has been transformed over the past decade based on a better understanding of disease biology, especially regarding molecular genetic drivers and relevant signaling pathways. Agents focusing on B-cell receptor (in particular Bruton tyrosine kinase [BTK]) and apoptosis (BCL2) targets have replaced chemoimmunotherapy (CIT) as the treatment standard. BTK and BCL2 inhibitor-based therapy has consistently shown prolonged progression-free survival and in some instances even increased overall survival against CIT in frontline phase 3 trials.

Ibrutinib in Early-Stage Chronic Lymphocytic Leukemia: The Randomized, Placebo-Controlled, Double-Blind, Phase III CLL12 Trial.

Purpose: The CLL12 trial reassesses the watch-and-wait consensus for early-stage chronic lymphocytic leukemia (CLL) in the context of targeted therapies.

Methods: The German CLL Study Group conducted a randomized, double-blind, placebo-controlled phase III trial with 363 patients with asymptomatic, treatment-naïve Binet stage A CLL at increased risk of progression to receive ibrutinib (n = 182) at a daily dose of 420 mg or placebo (n = 181). Additionally, 152 low-risk patients were allocated to the watch-and-wait group.

End Point Surrogacy in First-Line Chronic Lymphocytic Leukemia.

Purpose: Surrogate end points are commonly used to estimate treatment efficacy in clinical studies of chronic lymphocytic leukemia (CLL). This patient- and trial-level analysis describes the correlation between progression-free survival (PFS) and minimal residual disease (MRD) with overall survival (OS) in first-line trials for CLL.

Patients And Methods: First, patient-level correlation was confirmed using source data from 12 frontline German CLL Study Group (GCLLSG)-trials.

The NOTCH1 and miR-34a signaling network is affected by alterations in CLL.

In chronic lymphocytic leukemia (CLL), mutations or deletions on chromosome 17p lead to adverse prognosis and reduced levels of miR-34a, which targets NOTCH1. Also, hyperactivated NOTCH1 signaling is crucial for CLL progression. Here we explored the interaction between p53, miR-34a, and NOTCH1 in CLL.

Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study.

In the CLL14 study, patients with previously untreated chronic lymphocytic leukemia (CLL) and coexisting conditions were randomized to 12 cycles of venetoclax-obinutuzumab (Ven-Obi, n = 216) or chlorambucil-obinutuzumab (Clb-Obi, n = 216). Progression-free survival (PFS) was the primary end point. Key secondary end points included time-to-next-treatment (TTNT), rates of undetectable minimal residual disease (uMRD), overall survival (OS), and rates of adverse events.