People willing to trade treatment efficacy for reduced side effects in cancer therapies

(American Society of Hematology) When choosing their preferred treatment, people with chronic lymphocytic leukemia place the highest value on medicines that deliver the longest progression-free survival, but are willing to swap some drug efficacy for a reduced risk of serious adverse events according to a study published online in Blood Advances, a Journal of the American Society of Hematology. The study also suggests that factoring out-of-pocket costs into this decision-making process may significantly influence a patient's choice of treatment.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news

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Publication date: 10 December 2018Source: Cancer Cell, Volume 34, Issue 6Author(s): Delphine Merino, Gemma L. Kelly, Guillaume Lessene, Andrew H. Wei, Andrew W. Roberts, Andreas StrasserDefects in apoptotic cell death can promote cancer and impair responses of malignant cells to anti-cancer therapy. Pro-survival BCL-2 proteins prevent apoptosis by keeping the cell death effectors, BAX and BAK, in check. The BH3-only proteins initiate apoptosis by neutralizing the pro-survival BCL-2 proteins. Structural analysis and medicinal chemistry led to the development of small-molecule drugs that mimic the function of the BH3-only pr...
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research
We report the rapid development of resistance in chronic lymphocytic leukemia cells isolated from patients exposed to increasing doses of Navitoclax (ABT-263), a BH3 mimetic. To mimic such rapid development of chemoresistance, we have developed simple resistance models to three different BH3 mimetics, targeting BCL-2 (ABT-199), BCL-XL (A-1331852) or MCL-1 (A-1210477), in relevant haematological cancer cell lines. In these models, resistance could be attributed neither to consistent changes in expression levels of the anti-apoptotic proteins nor interactions among different pro- and anti-apoptotic BCL-2 family members. Usin...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Conclusions:These data suggest that venetoclax treatment results in loss of naïve but not memory T cells. Venetoclax did not affect the viability, the induction or frequency of memory T cells. In human in vitro experiments and in an in vivo syngeneic tumor model venetoclax did not antagonize the therapeutic effect of anti-PD-1. Contrary to our initial hypothesis, we find that modulation of the immune system by venetoclax may support its potential use for immune-based cancer therapy, as memory T-cells can rapidly acquire effector and cytotoxic function to eliminate cancer cells. Taken together, we provide evidence that...
Source: Blood - Category: Hematology Authors: Tags: 203. Lymphocytes, Lymphocyte Activation, and Immunodeficiency, including HIV and Other Infections: Poster III Source Type: research
Conclusions: LEO is a large and diverse cohort of newly diagnosed NHL patients and the first two years of enrollment reflects the broader United States NHL population. Enrollment is ongoing. This unique resource will enable examination of the interactions among a broad array of clinical and molecular factors and their impact on multiple outcomes, to improve prognostication, identify new approaches to improve outcomes and survivorship, and facilitate clinical trials using this infrastructure.DisclosuresFlowers: Acerta: Research Funding; Pharmacyclics/ Janssen: Consultancy; OptumRx: Consultancy; Janssen Pharmaceutical: Resea...
Source: Blood - Category: Hematology Authors: Tags: 627. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)-Results from Retrospective/Observational Studies: Poster I Source Type: research
Conclusions: At the 5-year follow-up of this phase III trial, there was a numerical but statistically not significant longer median OS (+4.7 months) in the OFA arm. As only few patients had the chance to receive a kinase inhibitor later, the study displays the survival of BFR CLL patients in the period prior to receiving small molecule inhibitors. This and other studies have demonstrated a longer PFS with the use of low-dose maintenance CD20 monoclonal antibody therapy vs not, a finding that may be re-explored in the new targeted therapeutic landscape in CLL. OFA is a safe option in multi-resistant advanced CLL cases.Discl...
Source: Blood - Category: Hematology Authors: Tags: 642. CLL: Therapy, excluding Transplantation Source Type: research
CD19-specific Chimeric Antigen Receptor (CTL019)-engineered T-cells provide a breakthrough for personalized cancer therapy. An anti-CD19 CAR gene with 41BB costimulatory domain is delivered into patient T-cells ex vivo using a lentiviral vector, expanded in culture and then reinfused into patients. While dramatically successful for some treatment-refractory cancers, a significant proportion of patients do not experience therapeutic levels of CAR T cell expansion - thus it is important to investigate factors driving successful expansion in responders in more detail. Here we have analyzed sites of lentiviral vector integrati...
Source: Blood - Category: Hematology Authors: Tags: 703. Adoptive Immunotherapy: Poster III Source Type: research
Conclusions: The most common regimen during LOT1 was bendamustine + rituximab, and was ibrutinib during LOT2 and LOT3.This study provides evidence that occurrence of AEs among patients with CLL receiving systemic anti-cancer therapy in the real-world setting is substantial and associated with significant health care cost. The economic burden associated with increased AEs underscores the need for treatments with fewer AEs.Figure.DisclosuresKabadi: AstraZeneca: Employment. Le: Optum: Employment; Optum/United Health Group: Equity Ownership. Dacosta Byfield: Optum/United Health Group: Equity Ownership; Optum: Employment. Olufa...
Source: Blood - Category: Hematology Authors: Tags: 904. Outcomes Research-Malignant Conditions: Real World Outcomes Source Type: research
ConclusionOur novel CLL culture method that allows cell proliferation along with our established functional in-vitro drug sensitivity screening platform enabled us to screen a number of patient samples and evaluate the sensitivity of a library of approved drugs and investigational drug candidates for CLL. Our analysis shows that several drugs may be effective for CLL and can be tested in drug combinations in order to identify synergistic effects. As a future perspective, we want to combine machine learning strategies with the experimental drug screening strategies to identify drug combinations and validate drug candidates ...
Source: Blood - Category: Hematology Authors: Tags: 802. Chemical Biology and Experimental Therapeutics: Poster III Source Type: research
Till 1998, a little was known about alternative forms of regulated cell death beside apoptosis. In present scenario, accumulating evidences suggest a form of programmed necrosis called Necroptosis which can be induced by various external stimuli including anticancer drugs, ionizing radiation, photodynamic therapy in the form of death domain receptor (DR) engagement by their respective ligands, TNF-alpha, Fas ligand (FasL) and TRAIL, under apoptosis deficient condition (caspase inhibitor),etc. receptor interacting protein-1 (RIP-1), a death domain containing kinase is the key molecule in necroptotic cell death pathway. On i...
Source: Oncology Reviews - Category: Cancer & Oncology Source Type: research
AbstractResistance to apoptosis is one of the hallmarks of cancer and members of the B-cell lymphoma 2 (BCL-2) family of proteins are central regulators of apoptosis. Many cancers become resistant to chemotherapy and apoptosis by up-regulating BCL-2 and other family members, making these proteins attractive targets for cancer therapy. Venetoclax is an orally administered, small-molecule apoptosis stimulant that targets BCL-2 proteins by acting as a BCL-2 homology domain 3 (BH3) mimetic. The drug is approved in the USA and EU as a monotherapy for the for the treatment of certain patients with chronic lymphocytic leukemia (C...
Source: Targeted Oncology - Category: Cancer & Oncology Source Type: research
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