Cll therapy

Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) is a relatively inert B lymphocyte proliferative disease. In recent years with the launch of new drugs, chemotherapy has been gradually replaced by targeted therapy, which significantly prolongs the survival of patients and reduces the side effects of treatment. At present, BTK inhibitors, PI3K inhibitors, spleen tyrosine kinase (SYK) inhibitors and BCL-2 inhibitors are the most studied targeted therapeutic drugs for CLL/SLL. This article reviews the research progress of different types of targeted therapeutic drugs in the treatment of CLL/SLL...

The potential prognostic influence of genetic aberrations on chronic lymphocytic leukaemia (CLL) can vary based on various factors, such as the immunoglobulin heavy variable (IGHV) status. We conducted an integrative analysis on genetic abnormalities identified through cytogenetics and targeted next-generation sequencing in 536 CLL patients receiving first-line chemo(immuno)therapies (CIT) as part of two prospective trials. We evaluated the prognostic implications of the main abnormalities, with specific attention to their relative impact according to IGHV status...

Elderly patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we retrospectively described the clinical features and outcomes of the first time infection of Omicron SARS-CoV-2 in 364 elderly patients with lymphoma enrolled in Jiangsu Cooperative Lymphoma Group (JCLG) between November 2022 and April 2023 in China. Median age was 69 years (range 60-92). 54.4% (198/364) of patients were confirmed as severe and critical COVID-19 infection...

Before targeted therapies, patients with higher-risk chronic lymphocytic leukemia (CLL) defined as del(17p) and/or TP53 mutation (TP53m), unmutated immunoglobulin heavy chain variable region genes (uIGHV), or complex karyotype (CK) had poorer prognosis with chemoimmunotherapy. Bruton tyrosine kinase inhibitors (BTKis) have demonstrated benefit in higher-risk patient populations with CLL in individual trials. To better understand the impact of the second-generation BTKi acalabrutinib, we pooled data from 5 prospective clinical studies of acalabrutinib as monotherapy or in combination with obinutuzumab (ACE-CL-001, ACE-CL-003, ELEVATE-TN, ELEVATE-RR, and ASCEND) in patients with higher-risk CLL in treatment-naive (TN) or relapsed/refractory (R/R) cohorts...

Pharmacotherapy options for chronic lymphocytic leukaemia (CLL) have expanded significantly in recent years. These options include chemotherapy, chemoimmunotherapy and signalling pathway inhibitors. A notable shift in the treatment landscape began with the widespread adoption of ibrutinib in 2016. This analysis of claims data focuses on understanding how the use of novel therapies has evolved in clinical practice over the past decade in Germany. Anonymized claims data (2010-2022) from German statutory health insurance was used, covering patient demographics, treatments, and prescriptions...

INTRODUCTION: There has been a paradigm shift in the treatment of chronic lymphocytic leukemia (CLL) over the past decade. With the advent of self-administered targeted oral anticancer agents (OAAs), the treatment of CLL has begun to shift from the infusion clinic to the patient's home. This introduced new challenges including patient non-adherence, class-specific adverse effects, and financial toxicity to treatment. In this paper, we discuss a structured approach to identifying and addressing barriers to optimal patient outcomes...

PURPOSE: Real-world evidence comparing health care resource use (HRU) and costs between novel targeted therapies among patients with chronic lymphocytic leukemia (CLL) is lacking. We compared all-cause and CLL-specific HRU and costs between patients initiated on B-cell lymphoma 2 inhibitor (venetoclax)- or Bruton tyrosine kinase inhibitor (BTKi)-based regimens in the second-line (2L) setting. METHODS: This is a retrospective observational study using Optum Clinformatics Data Mart of adult patients with CLL/small lymphocytic lymphoma who received 2L venetoclax- or BTKi-based regimens (January 2018-December 2021) for the first time and had ≥one CLL diagnostic claim after 2L initiation and ≥two claims for venetoclax or BTKi...

We evaluated the prognostic value of the Chronic Lymphocytic Leukemia International Prognostic Index (CLL-IPI) using a pooled dataset of CLL-patients treated first-line with targeted drugs (N=991) or chemoimmunotherapy (N=1,256). With a median observation time of 40.5 months, the 3-year progression-free survival (PFS)-rates for targeted drug-treated patients varied by CLL-IPI risk group: 96.5% (low), 87.6% (intermediate), 82.4% (high), and 78.7% (very high). Differences between consecutive CLL-IPI risk groups were observed for intermediate vs...

The molecular landscape of chronic lymphocytic leukemia (CLL) has been extensively characterized, and various potent prognostic biomarkers were discovered. The genetic composition of the B-cell receptor (BCR) immunoglobulin (IG) was shown to be especially powerful for discerning indolent from aggressive disease at diagnosis. Classification based on the IG heavy chain variable gene (IGHV) somatic hypermutation status is routinely applied. Additionally, BCR IGH stereotypy has been implicated to improve risk stratification, through characterization of subsets with consistent clinical profiles...

In the last few years, several agents targeting molecules that sustain the survival and the proliferation of chronic lymphocytic leukemia (CLL) cells have become clinically available. Most of these drugs target surface proteins, such as CD19 or CD20, via monoclonal or bispecific monoclonal antibodies (BsAbs), CAR T cells, intracellular proteins like BTK by using covalent or non-covalent inhibitors or BCL2 with first or second generation BH3-mimetics. Since the management of CLL is evolving quickly, in this review we highlighted the most important innovative treatments including novel double and triple combination therapies, CAR T cells and BsAbs for CLL...

Chromosomal aberrations are a common feature of cancer and can fuel cancer progression and treatment resistance. In chronic lymphocytic leukemia (CLL), the presence of multiple chromosomal aberrations is commonly referred to as "genomic complexity" or "complex karyotype"- (CKT). In the context of chemo- and chemoimmunotherapy, genomic complexity is associated with poor response to treatment and short survival, while some targeted therapies are able to mitigate its adverse prognostic impact. This article reviews currently available data and literature on the role of genomic complexity in CLL...

UNLABELLED: Chronic lymphocytic leukaemia (CLL) is a lymphoproliferative disorder characterised by an accumulation of monoclonal B lymphocytes, with an increased risk of secondary cancers. The coexistence of CLL and chronic myeloid leukaemia (CML) is a rare phenomenon, with three main types being classified: CML preceding CLL, CLL preceding CML and simultaneous occurrence. The coexistence of these chronic leukaemias poses a complex clinical challenge, with the underlying mechanisms of their association remaining enigmatic...

Leukemia caused by environmental chemical pollutants has attracted great attention, the malignant leukemic transformation model of TK6 cells induced by hydroquinone (HQ) has been previously found in our team. However, the type of leukemia corresponding to this malignant transformed cell line model needs further study and interpretation. Furthermore, the molecular mechanism of malignant proliferation of leukemic cells induced by HQ remains unclear. This study is the first to reveal the expression of aberrant genes in leukemic cells of HQ-induced malignant transformation, which may correspond to chronic lymphocytic leukemia (CLL)...

Chronic Lymphocytic Leukemia (CLL) patients have a defective expression of the proapoptotic protein p66Shc and of its transcriptional factor STAT4, which evoke molecular abnormalities, impairing apoptosis and worsening disease prognosis and severity. p66Shc expression is epigenetically controlled and transcriptionally modulated by STAT4; epigenetic modifiers are deregulated in CLL cells and specific histone deacetylases (HDACs) like HDAC1, are overexpressed. Reactivation of STAT4/p66Shc expression may represent an attractive and challenging strategy to reverse CLL apoptosis defects...

OBJECTIVE: To investigate the association between serum immunoglobulin G (IgG) concentrations and the incidence of infections in patients with chronic lymphocytic leukemia (CLL) and secondary immunodeficiency receiving treatment with Privigen. MATERIALS AND METHODS: Data was analyzed from a non-interventional study conducted in 31 centers in Germany and 1 in Austria. Adult CLL patients with hypogammaglobulinemia and recurrent infections were allowed to enter the study upon signing informed consent, if a prior decision for treatment with Privigen had been made...

INTRODUCTION: The variable clinical course of chronic lymphocytic leukemia (CLL) and the lack of consensus on follow-up and treatment strategies have necessitated a prognostic model for identifying high-risk patients at the time of diagnosis. METHODS: We involved a retrospective analysis of demographic and clinical characteristics of 212 patients diagnosed with Binet stage A CLL and thus eligible for risk stratification by both the International Prognostic Score for Early-stage CLL (IPS-E) and the alternative IPS-E (AIPS-E)...

PURPOSE: Outcomes for Richter transformation (RT) are poor with current therapies. The efficacy and safety of anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T) for RT are not established. METHODS: We performed an international multicenter retrospective study of patients with RT who received CAR-T. Patient, disease, and treatment characteristics were summarized using descriptive statistics, and modeling analyses were used to determine association with progression-free survival (PFS) and overall survival (OS)...

Leukemia is a malignant clonal disease of hematopoietic stem cells, which accounts for about 3% of the total incidence of tumors and is particularly prevalent among children and adolescents. It mainly includes four types of leukemia, namely ALL, AML, CLL, and CML, which are often aggressive and challenging diseases to treat. Several signaling pathways are dysregulated in almost all types of leukemia, such as JAK, PI3K, and MAPK, and others are dysregulated in specific types of leukemia, like Wnt/β-catenin, Hedgehog, FLT3, Bcr-Abl, and so on...

In the last decade, novel agents such as BTK and BCL-2 inhibitors have revolutionized treatment of CLL/SLL, with clinical trials showing improved overall survival compared to chemotherapeutic agents. However, studies examining whether they have improved overall survival at the population level are lacking. We evaluated this by conducting a retrospective analysis of CLL/SLL patients registered in the National Cancer Institute's surveillance epidemiology and end results (SEER) database, analyzing overall survival (OS) in periods pre- and post-availability of novel agents, along with demographic information...

To assess the impact of first-line treatment with targeted agents (TAs) or fludarabine, cyclophosphamide, and rituximab (FCR)-based chemo-immunotherapy (CIT) on overall survival (OS) compared to age- and sex-matched individuals in the general population, we conducted an aggregated analysis of phase 3 clinical trials, including the two FLAIR sub-studies, ECOG1912, and CLL13 trials. The restricted mean survival time (RMST), an alternative measure in outcome analyses capturing OS changes over the entire history of the disease, was used to minimize biases associated with the short follow-up time of trials...