Revolution of Chronic Lymphocytic Leukemia Therapy: the Chemo-Free Treatment Paradigm

AbstractPurpose of ReviewOver the last years, targeted anticancer therapy with small molecule inhibitors and antibodies has much replaced chemoimmunotherapy, which has been the gold standard of care for patients with chronic lymphocytic leukemia (CLL). Here we give an overview of novel targeted agents used in therapy of chronic lymphocytic leukemia, as well as efforts to overcome resistance development, focusing on approved drugs since they gained high relevance in clinical practice.Recent FindingsNovel agents moved to the forefront as a treatment strategy of CLL due to their outstanding efficacy, almost irrespectively of the underlying genetic features. Inhibition of Bruton ’s tyrosine kinase (BTK), a key molecule in the B cell receptor pathway, achieved dramatic efficacy even in poor-risk and chemo-refractory patients. Further success was accomplished with venetoclax, which specifically inhibits anti-apoptotic BCL2 and induces apoptosis of CLL cells.SummaryInhibition of BTK or BCL2 is very effective and induces prolongation of progression-free and overall survival. Approved combination treatments such as venetoclax or ibrutinib with obinutuzumab show high responses rates and long remission durations. However, evolution and selection of subclones with continuous treatment leads to resistance towards these novel drugs and disease relapse. Hence, comparison of sequential treatment with combinations and discontinuation of therapy are important aspects which need to be inv...
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research

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Cancer patients are a population at high risk of contracting COVID-19 and, also of developing severe complications due to the infection, which is especially true when they are undergoing immunosuppressive treatment. Despite this, they had still to go to hospital to receive chemotherapy during lockdown. In this context, we have evaluated the psychological status of onco-hematological outpatients receiving infusion and not deferrable anti-neoplastic treatment for lymphoproliferative neoplasms, with the aim of both measuring the levels of post-traumatic symptoms, depression, and anxiety during the pandemic and also of investi...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions: CLL imposes a significant HRQoL and economic burden. Our systematic review shows that an unmet need persists in CLL for treatments that delay progression while minimizing AEs. Studies suggest targeted therapies may reduce the economic burden of CLL but longer follow-up data are needed. PMID: 32634056 [PubMed - as supplied by publisher]
Source: Current Medical Research and Opinion - Category: Research Tags: Curr Med Res Opin Source Type: research
Chronic lymphocytic leukemia (CLL) is generally considered an indolent disease of the elderly, but more aggressive subtypes have been identified based on clinical and biological features1. In particular, patients who are refractory or early relapsing (R/R) after chemoimmunotherapy (CIT) and patients carrying 17p deletion (del17p) and/or p53 mutation (TP53mut) have shown poor survival ranging between 12 and 24 months after CIT2. For these reasons, young patients have been conventionally considered good candidates for allogeneic stem cell transplantation (alloSCT), with the first recommendations formally defined in 2007 by t...
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Authors: Xu L, Jiao J, Sun X, Sang W, Gao X, Yang P, Yan D, Song X, Sun C, Liu M, Qin Y, Tian Y, Zhu F, Zeng L, Li Z, Xu K Abstract Cladribine is a purine nucleoside analog used to treat B-cell chronic lymphocytic leukemia and hairy cell leukemia, also functions as an inhibitor of DNA synthesis to block the repair of the damaged DNA. The therapeutic role of cladribine against diffuse large B-cell lymphoma cells (DLBCL) is still undefined. In the present study, we demonstrated that cladribine inhibited cell proliferation and induced G1 phase arrest in human DLBCL cells. Furthermore, we showed that cladribine induced...
Source: International Journal of Medical Sciences - Category: Biomedical Science Tags: Int J Med Sci Source Type: research
Source: Annals of Hematology - Category: Hematology Source Type: research
dano Francesca Romana Mauro The role of positron emission tomography/computed tomography (PET/CT) in identifying Richter Syndrome (RS) is well established, while its impact on the survival of patients with chronic lymphocytic leukemia (CLL) has been less explored. The clinical characteristics and PET/CT data of 40 patients with a biopsy-proven CLL who required frontline chemoimmunotherapy, FCR (fludarabine, cyclophosphamide, rituximab) in 20 patients, BR (bendamustine, rituximab) in 20, were retrospectively analyzed. Standardized uptake volume (SUVmax) values ≥ 5 were observed more frequently in patients with ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Conclusion: In CLL, a neoplastic antigen-specific B-cell clone proliferates, and the progeny cells accumulate and outgrow other B cells, leading to immune deficiency. Considering the low humoral immune response and ineffective clearance of SARS-Cov-2 in CLL patients, the follow-up and home quarantine period should be extended. We need further studies to clarify suspending or continuing CLL therapy during COVID infection. For those patients who are prone to progression to severe disease, administering humoral immunity therapies can help to prevent disease progression and quickly meet the cure criteria.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Abstract Chronic lymphocytic leukemia is a well-defined lymphoid neoplasm with very heterogeneous biological and clinical behavior. The last decade has been remarkably fruitful in novel findings elucidating multiple aspects of the pathogenesis of the disease including mechanisms of genetic susceptibility, insights into the relevance of immunogenetic factors driving the disease, profiling of genomic alterations, epigenetic subtypes, global epigenomic tumor cell reprogramming, modulation of tumor cell and microenvironment interactions, and dynamics of clonal evolution from early steps in monoclonal B cell lymphocyto...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
CONCLUSIONS: Taken together, our NGS immunoprofiling data suggest that BcRi retain T cell clones that may have developed against CLL-associated antigens. Phenotypic and immune synapse bioassays support a concurrent restoration of functionality, mostly evident for R-ID, arguably contributing to clinical response. PMID: 32616500 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Conclusion: No statistically significant radiation associations were observed among 114,270 nuclear weapons test participants followed for up to 65 y. The 95% confidence limits were narrow and exclude mortality risks per unit dose that are two to four times those reported in other investigations. Significantly elevated SMRs were seen for mesothelioma and asbestosis, attributed to asbestos exposure aboard ships. PMID: 32602389 [PubMed - as supplied by publisher]
Source: International Journal of Radiation Biology - Category: Radiology Tags: Int J Radiat Biol Source Type: research
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