- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Leukeran (chlorambucil) / GSK, Imbruvica (ibrutinib) / AbbVie, J&J
IMPROVED SURVIVAL OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA BETWEEN 1998-2022, INCLUDING THE ERA OF TARGET THERAPIES WITH BCL2 AND BTK INHIBITORS. (Poster area) - May 12, 2023 - Abstract #EHA2023EHA_2226; When the analysis was done on the basis of treatment given: the 6-year OS was 85% for patients treated with Venetoclax, 68% for Ibrutinib, 65% for FCR, and 60% for BR or Chlorambucil+ anti-CD20 therapy compared to 35% for patients treated with chlorambucil+/- prednisone. We found marked improvements in relative survival of the population level, following fundamental changes in first-line therapy of patients diagnosed with CLL.Figure 1: Overall survival of patients with CLL during the last 24 years, divided into 3 eras: before 2010, 2010- 2017, and between 2017-2022 B-CLL
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
VENETOCLAX-OBINUTUZUMAB FOR PREVIOUSLY UNTREATED CHRONIC LYMPHOCYTIC LEUKEMIA: 6-YEAR RESULTS OF THE RANDOMIZED CLL14 STUDY (Panorama 1) - May 12, 2023 - Abstract #EHA2023EHA_893; These data confirm a long-term PFS benefit of fixed-duration Ven-Obi treatment compared to Clb-Obi, including patients with high-risk CLL.Fiveyears after completing Ven-Obi, over half of patients remained in remission,and over 60% had not required second-linetreatment.The 1-year Ven-Obi regimen is an effectivefixed-duration option for patients with CLL and coexisting conditions. Keywords: Obinutuzumab, Venetoclax, B-CLL, Chronic lymphocytic leukemia
- |||||||||| Mustargen (mechlorethamine) / Recordati, Leukeran (chlorambucil) / GSK
Journal: Antitumor activity and mechanisms of dual EGFR/DNA-targeting strategy for the treatment of lung cancer with EGFR mutation. (Pubmed Central) - May 1, 2023 Box plot of the number of nephrotic syndrome relapses during the two yearsperiod before and after rituximab administration in the study group. In this work, fifteen 4-anilinoquinazoline derivatives bearing nitrogen mustard or hemi mustard moieties were designed and synthesized as dual EGFR-DNA targeting anticancer agents...Compound 6g emerged as the most potent derivative against mutant-type H1975 cells with IC value of 1.45
- |||||||||| A study of frontline therapy in adults >80 years with chronic lymphocytic leukemia (CLL). (On Demand | Hall A; Poster Bd # 425) - Apr 26, 2023 - Abstract #ASCO2023ASCO_3653;
In this work, fifteen 4-anilinoquinazoline derivatives bearing nitrogen mustard or hemi mustard moieties were designed and synthesized as dual EGFR-DNA targeting anticancer agents...Compound 6g emerged as the most potent derivative against mutant-type H1975 cells with IC value of 1.45 The median OS was 3.3 years (95% CI 2.6
- |||||||||| Farydak (panobinostat) / Secura Bio, Leukeran (chlorambucil) / GSK, Matulane (procarbazine hydrochloride) / Leadiant Biosci
MicroOrganoSpheres as a clinically applicable precision oncology platform for the discovery of novel therapies in colorectal cancer. (On Demand | Hall A; Poster Bd # 292) - Apr 26, 2023 - Abstract #ASCO2023ASCO_3110; These results demonstrate that our MOS pipeline can be used as a precision oncology platform within a clinically applicable time frame to potentially guide therapy. We are now in the process of correlating drug response in MOS to patient outcome data and these findings will be presented at the annual meeting.
- |||||||||| Leukeran (chlorambucil) / GSK
Pharmacologic tumor PDL1 depletion as a novel approach to overcome treatment resistance (P577) (Exhibit Hall; Poster Board No. P577) - Apr 11, 2023 - Abstract #IMMUNOLOGY2023IMMUNOLOGY_332; The PDD chlorambucil (alkylating agent) selectively depleted tumor PDL1 in vivo and sensitized ?PDL1-resistant tumors to ?PDL1 in a tumor PDL1 and NK cell-dependent manner. Thus, PDDs deplete tumor PDL1 to inhibit its pathologic cell-intrinsic signals, induce novel treatment vulnerabilities, improve tumor immunogenicity, and are rapidly translatable.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Journal, HEOR, Cost-effectiveness, Cost effectiveness: Cost-effectiveness of Venetoclax plus Obinutuzumab versus Chlorambucil plus Obinutuzumab for the First-Line Treatment of Adult Patients with Chronic Lymphocytic Leukemia - an extended societal view. (Pubmed Central) - Apr 4, 2023 P3 Thus, PDDs deplete tumor PDL1 to inhibit its pathologic cell-intrinsic signals, induce novel treatment vulnerabilities, improve tumor immunogenicity, and are rapidly translatable. Our study demonstrated VenO being dominant over ClbO in treatment-na
- |||||||||| Calquence (acalabrutinib) / AstraZeneca
Journal, HEOR, Cost-effectiveness, Cost effectiveness: Cost-effectiveness of acalabrutinib regimens in treatment-na (Pubmed Central) - Mar 30, 2023 Probabilistic sensitivity analysis showed the probability of acalabrutinib monotherapy being cost effective as 59% to 73% at a $100,000-to-150,000/QALY willingness-to-pay threshold; the probability of acalabrutinib + obinutuzumab being cost effective ranged from 34% to 51%. Although the analysis is limited by uncertainty in postprogression survival outcomes, acalabrutinib monotherapy is likely cost effective vs chlorambucil + obinutuzumab in treatment-na
- |||||||||| Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
A RARE PRESENTATION OF ACUTE KIDNEY INJURY IN CHRONIC LYMPHOCYTIC LEUKEMIA () - Mar 28, 2023 - Abstract #ISNWCN2023ISN_WCN_864; The unusual development of acute kidney injury without a clear aetiology prompted the renal biopsy, which showed disease infiltrates. His subsequent initiation of chemotherapy was critical and resulted in recovery of renal function.
- |||||||||| Leukeran (chlorambucil) / GSK
Journal: Clinical characteristics and outcomes of Mott cell lymphoma in nine miniature dachshunds. (Pubmed Central) - Mar 24, 2023 His subsequent initiation of chemotherapy was critical and resulted in recovery of renal function. MCL in miniature dachshunds can be recognised as a peculiar type of B-cell lymphoma occurring in relatively young dogs as an alimentary form and has a longer survival compared with typical alimentary large cell lymphoma.
- |||||||||| Calquence (acalabrutinib) / AstraZeneca
Enrollment closed, Trial completion date, Trial primary completion date: Study of Acalabrutinib Versus Chlorambucil Plus Rituximab in Adult Subjects With Previously Untreated Chronic Lymphocytic Leukemia (clinicaltrials.gov) - Mar 8, 2023 P3, N=117, Active, not recruiting, MCL in miniature dachshunds can be recognised as a peculiar type of B-cell lymphoma occurring in relatively young dogs as an alimentary form and has a longer survival compared with typical alimentary large cell lymphoma. Recruiting --> Active, not recruiting | Trial completion date: Oct 2024 --> Jun 2024 | Trial primary completion date: Oct 2024 --> Jun 2024
- |||||||||| Leukeran (chlorambucil) / GSK
Journal: Facile Preparation and Photoactivation of Prodrug-Dye Nanoassemblies. (Pubmed Central) - Mar 7, 2023 A photocleavable boron-dipyrromethene-chlorambucil (BC) prodrug was first synthesized...The nanoparticles displayed enhanced cytotoxicity under light irradiation at 530 nm compared with the non-irradiated nanoparticles and irradiated free BC prodrug. This protocol provides a reference
- |||||||||| Leukeran (chlorambucil) / GSK
Journal: Chlorambucil-Loaded Graphene-Oxide-Based Nano-Vesicles for Cancer Therapy. (Pubmed Central) - Feb 25, 2023 The rate of drug release from the CHL-loaded GO was 25% and 75% after 24 h. The biotoxicity study in terms of % cell viability of CHL-free and CHL-loaded GO against human cervical adenocarcinoma cell line was found to have lower cytotoxicity of CHL-loaded nano-vesicles (IC = 18 ?M) as compared to CHL-free (IC = 8 ?M). It is concluded that a high drug-loading efficiency and controlled release with excellent biotoxicity of CHL-GO offers an excellent application in the biomedical field.
- |||||||||| Mustargen (mechlorethamine) / Recordati, Leukeran (chlorambucil) / GSK
Reactive oxygen species (ROS)-activated prodrugs: Mechanism and combination strategy (Hall F-H (Indiana Convention Center)) - Feb 14, 2023 - Abstract #ACSSp2023ACS_SP_2769; Nitrogen mustard containing compounds are well-known for their high reactivity towards DNA, therefore being used for the treatment of different types of cancers...FAN-NM-CH3 was found to be 10 times more cytotoxic than chlorambucil and 16 times more active than melphalan, which are known for their lowest-limiting toxicity within its class of compounds...Although the exact mechanism of its superior activity and selectivity in vivo is yet to be determined. In this work, we measured the extracellular H2O2 production level in MDA-MB-468 cells, evaluated the effects of ROS quencher/enhancer on prodrug toxicity to define a correlation between H2O2 level and efficacy, and understood the mechanism of drug action as a DNA-alkylating agent through evaluation of gene expression that demonstrates an upregulated tumor protein p53.
- |||||||||| Leukeran (chlorambucil) / GSK
Journal: Comparative analysis of chlorambucil-induced DNA lesion formation and repair in a spectrum of different human cell systems. (Pubmed Central) - Jan 31, 2023 In conclusion, LC-MS/MS analyses combined with the rFADU technique are powerful tools to study the molecular mechanisms of NM-induced DNA damage and repair. By applying these methods to a spectrum of human cell systems of different origin and transformation status, we obtained insight into the cell-type specific repair of different CLB-induced DNA lesions, which may help identify novel resistance mechanisms of tumors and define molecular targets for therapeutic interventions.
- |||||||||| Leukeran (chlorambucil) / GSK, Lynparza (olaparib) / Merck (MSD), AstraZeneca
Journal, BRCA Biomarker, PARP Biomarker: Discovery of a potent olaparib-chlorambucil hybrid inhibitor of PARP1 for the treatment of cancer. (Pubmed Central) - Jan 27, 2023 Further analysis revealed the effects of C2 in induction of G2/M phase cell cycle arrest and promotion of apoptosis. Collectively, the olaparib-chlorambucil hybrid molecule (C2) could be utilized as a lead compound for further drug design.
- |||||||||| Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Retrospective data, Review, Journal: Immunosuppressive treatment for idiopathic membranous nephropathy: An updated network meta-analysis. (Pubmed Central) - Jan 26, 2023 The efficacy of RTX is not inferior to the CTX (OR 0.81; CI 0.32, 2.01), and the level of evidence was moderate; CSA was not as effective as RTX, and the difference was statistically significant with moderate evidence (OR 2.98, CI 1.00, 8.91). In summary, we recommend CTX and RTX as the first-line drug for IMN treatment.
- |||||||||| Calquence (acalabrutinib) / AstraZeneca
Enrollment closed, Trial completion date, Combination therapy, Monotherapy: ELEVATE-TN: Acalabrutinib, Obinutuzumab and Chlorambucil in Treatment na (clinicaltrials.gov) - Jan 10, 2023 P3, N=535, Active, not recruiting, Clinical Trial Registration: NCT01722487 (ClinicalTrials.gov) Clinical Trial Registration: NCT01724346 (ClinicalTrials.gov). Unknown status --> Active, not recruiting | Trial completion date: Jul 2021 --> Sep 2025
- |||||||||| Leukeran (chlorambucil) / GSK
Biomarker, Journal, Tumor microenvironment: Tumor microenvironment-activated multi-functional nanodrug with size-enlargement for enhanced cancer phototheranostics. (Pubmed Central) - Dec 7, 2022 In a tumor microenvironment (TME) with excessive glutathione (GSH), CPMI undergoes a cascade reaction to generate the phototheranostic molecule NPMI and the chemodrug chlorambucil, simultaneously switching on the near-infrared (NIR) fluorescence, photothermal effect, and drug release...The enhanced tumor inhibition efficiency of the nanodrug is confirmed through activatable chemo-photothermal therapy. This work paves the way for the design of activatable phototheranostic agents for accurate cancer diagnosis and treatment.
- |||||||||| Systematic Review and Network Meta-Analysis of Frontline Targeted Therapy in Chronic Lymphocytic Leukemia Shows Comparable Efficacy but Distinct Toxicity () - Nov 29, 2022 - Abstract #ASH2022ASH_7629;
Establishing the absence of significant difference in efficacy of frontline targeted therapies in CLL allows the clinician and patient to select therapy based on other factors, namely planned duration, toxicity profile, medication interactions, and cost.Figure 1. 24-month PFS Network and Forest Plot1Chl = Chlorambucil; Acal = Acalabrutinib; Acal/Obin = Acalabrutinib/Obinutuzumab; BR = Bendamustine/Rituximab; Chl/Ofa = Chlorambucil/Ofatumumab; Chl/Ritux = Chlorambucil/Rituximab; Chl/Ritux + Mtn = Chlorambucil/Rituximab + maintenance Rituximab; Flu = Fludarabine; Ibr = Ibrutinib; Ibr/Obin = Ibrutinib/Obinutuzumab; Ibr/Ritux = Ibrutinib/Rituximab; Ibr/Ven = Ibrutinib/Venetoclax; Ven/Obin = Venetoclax/Obinutuzumab; Zan = Zanubrutinib
- |||||||||| Leukeran (chlorambucil) / GSK
Journal: Tumor Targeting by Conjugation of Chlorambucil with Zwitterionic Near-Infrared Fluorophore for Cancer Phototherapy. (Pubmed Central) - Nov 27, 2022 Furthermore, the tumor tissue targeted by the CLB-ZW800 conjugate was exposed to 808 nm NIR laser irradiation to generate photothermal energy and promote apoptotic cell death for the effective PTT of cancer. Therefore, this study provides a feasible strategy for developing bifunctional PTT agents capable of tumor-targeted imaging and phototherapy by the conjugation of small molecule drugs with the versatile zwitterionic NIR fluorophore.
- |||||||||| Leukeran (chlorambucil) / GSK
Journal: Anti-Cancer Effect of Chlorambucil Enhanced by Chiral Phthalidyl Promoiety. (Pubmed Central) - Nov 26, 2022 It was found that proper chirality within the promoiety had noticeably better in vivo pharmacological effects than the parent drug, the enantiomer and racemic mixture. This merit perhaps could be extended from the phthalidyl prodrugs to other chirality containing prodrugs.
- |||||||||| Leukeran (chlorambucil) / GSK
Biomarker, Journal, Tumor Mutational Burden, Tumor microenvironment, Pan tumor: Pan-cancer analysis of trophinin-associated protein with potential implications in clinical significance, prognosis, and tumor microenvironment in human cancers. (Pubmed Central) - Nov 25, 2022 Collectively, these findings indicated a significant correlation between TROAP expression and malignant phenotype, functional mechanism, survival possibility, TME, therapeutic potential, and prediction of drug sensitivity in various cancers. Hence, TROAP is a promising biomarker and therapeutic target for predicting cancer outcomes.
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