Leukeran (chlorambucil) / GSK 
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  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie, Leukeran (chlorambucil) / GSK
    Real-World Outcomes of Second-Line Chronic Lymphocytic Leukemia Treatments: Retrospective Analysis of the Brazilian Registry of CLL (ENMCC - Hall D) -  Nov 4, 2022 - Abstract #ASH2022ASH_4504;    
    Over the reported period, second-line CLL treatments in Brazil were mostly chemotherapy- or chemoimmunotherapy-based, with unfavorable outcomes associated with CHOP/CVP-like regimens or monoclonal antibodies +/- steroids. While the adoption of targeted therapies was associated with longer TTNT and OS, access to these agents is still very limited in the public setting.
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie
    Real World Comparison of Bruton Tyrosine Kinase Inhibitors and Venetoclax in Patients Diagnosed with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (ENMCC - Hall D) -  Nov 4, 2022 - Abstract #ASH2022ASH_4497;    
    While these novel agents have been favorably compared to chlorambucil-based therapy and other chemoimmunotherapy (CIT) combinations, direct comparisons between BTKi and BCL-2i have not been conducted in any line of therapy...BTKi was compared to BCL-2i + obinutuzumab (O) in the 1L and to BCL-2i + any CD20 mAb in the 2L...This result has immediate implications for tx selection in current clinical practice, may serve to inform the results of ongoing randomized studies and provides insight for future clinical trial design. Future studies will include longer pt follow-up, additional pts added to the dataset, assessment of discontinuation reasons for each class of therapy and assessment of TTNT stratified by key molecular / genetic prognostic factors.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Journal:  Are cytostatic drugs in surface waters a potential threat? (Pubmed Central) -  Oct 28, 2022   
    Furthermore, cutting-edge data on the occurrence of two cytostatic drugs is provided; up to the authors' best knowledge, flutamide and mycophenolate mofetil have never been monitored in worldwide surface waters...Despite bicalutamide being the cytostatic most frequently detected, the highest concentration was recorded for cyproterone (19 ± 3 ng/L)...Still, attending to the carcinogenicity of some of these compounds (e.g., cyclophosphamide, chlorambucil, etoposide and tamoxifen), health risks might always be expected, regardless of the contamination level. Furthermore, health risks associated with synergic effects and/or long-term exposures cannot be ruled out, even for the remaining cytostatics/exposure contexts.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Biomarker, Journal, Tumor microenvironment:  Glycyrrhetinic acid modified chlorambucil prodrug for hepatocellular carcinoma treatment based on DNA replication and tumor microenvironment. (Pubmed Central) -  Oct 23, 2022   
    In addition, GA improved the tumor microenvironment by increasing the proportion of CD4T and CD8T cells at the tumor site, and promoting the differentiation of CD4T cells into Th1 cells, thereby reducing the proportion of Treg and Th2 cell subsets, so as to offset the adverse factors of CLB against tumor immunity. By interfering with DNA replication and modulating the tumor microenvironment, GA/CLB-CS micelles enabled the effective treatment of liver cancer.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Patients’ Perspective On The Burden Of Hypereosinophilic Syndrome (Exhibit Hall (Upper Concourse); Monitor 17) -  Oct 10, 2022 - Abstract #ACAAI2022ACAAI_794;    
    Of note, most patients (55.5%) were satisfied with monoclonal antibody injectable medications. Conclusion Understanding the multifactorial burden and heterogeneity of HES directly from patients highlights key unmet needs of this population and offers a basis upon which diagnosis, care, and outcomes may be improved.
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
    Journal, HEOR, Combination therapy:  Cost-utility analysis of venetoclax in combination with obinutuzumab as first-line treatment of chronic lymphocytic leukaemia in Spain. (Pubmed Central) -  Oct 9, 2022   
    Conclusion Understanding the multifactorial burden and heterogeneity of HES directly from patients highlights key unmet needs of this population and offers a basis upon which diagnosis, care, and outcomes may be improved. Venetoclax in combination with obinutuzumab is an efficient and  dominant alternative for treating previously untreated patients with chronic lymphocytic leukaemia compared to the available  alternatives and from the perspective of the Spanish National Health System.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Pharmacologic tumor PDL1 depletion as a translational approach to inhibit tumor-intrinsic PDL1 signals and create novel treatment vulnerabilities (Hall C) -  Oct 6, 2022 - Abstract #SITC2022SITC_788;    
    Results We identified the FDA-approved, structurally similar cephalosporin antibiotics cefepime and ceftazidime and the alkylating agent chlorambucil as PDDs with distinct signaling and treatment consequences...We identify several FDA-approved drugs that deplete tumor PDL1, disrupt its pathogenic tumor-intrinsic signals, and induce small molecule synthetic lethality and anti-PDL1 efficacy improvement. We identified other PDDs offering opportunities as translational targets, which we are now progressing to phase I clinical trials.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Journal:  Photoresponsive prodrug-dye nanoassembly for in-situ monitorable cancer therapy. (Pubmed Central) -  Oct 1, 2022   
    In this study, we report a simple strategy of co-assembling boron-dipyrromethene-chlorambucil prodrug and near-infrared dye IR783 to fabricate photoresponsive nanoassemblies, which achieved both high prodrug loading capacity (~99%) and efficient light-triggered prodrug activation...Systemic administration of the nanoparticles and localized light irradiation at tumor sites enabled monitorable and efficient drug release in vivo. Our results demonstrate that such prodrug-dye co-assembled nanomedicine is a promising formulation for photoresponsive drug delivery, which would advance the translation of photoresponsive nanomedicines.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Journal:  Potent Chlorambucil-Platinum(IV) Prodrugs. (Pubmed Central) -  Oct 1, 2022   
    Notably, 56CLB was exceptionally potent in HT29 colon, Du145 prostate, MCF10A breast, MIA pancreas, H460 lung, A2780, and ADDP ovarian cell lines, with GI values ranging between 2.7 and 21 nM. Moreover, significant production of reactive oxygen species was detected in HT29 cells after treatment with PCLB, 5CLB, and 56CLB up to 72 h compared to chlorambucil and the platinum(II) and (IV) precursors.
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie, Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
    Patterns of treatment and outcomes in CLL patients in Australia: An analysis of the population-wide pharmaceutical benefits scheme dataset (Summit 2) -  Oct 1, 2022 - Abstract #ESMOAsia2022ESMO_Asia_438;    
    In the frontline setting, fludarabine-chlorambucil-rituximab use has decreased while chlorambucil + CD20 agents usage has increased...The median duration of ibrutinib therapy was 24 months (95%CI, 19-38) and 19 months (95%CI, 11-not reached (NR)) for venetoclax...Conclusions In the Australian setting, CLL treatment patterns have significantly changed since the introduction of novel therapies. Median OS in the front-line setting is more than 10 years, while the R/R population has a shorter OS observed.
  • ||||||||||  Leukeran (chlorambucil) / GSK, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
    Clinical Signifi cance of B-Cell Receptor Stereotype in CLL () -  Sep 22, 2022 - Abstract #SOHO2022SOHO_386;    
    This suggests that CIT may be less optimal for subset #2 patients, while also highlighting the usefulness of this information for risk stratifi cation of patients, a practice already followed by different study groups worldwide. In that regard, it is relevant to mention the results of the NCRI FLAIR trial, where a hazard ratio for disease progression and death of 0.32 was reported for subset #2 patients treated with FCR versus IR, though not reaching statistical signifi cance (p =0.191), likely due to low numbers (FCR, n =20; IR, n =26).21 Subset #8 includes patients with U-CLL expressing BcR IG encoded by the IGHV4-39/IGKV1(D)-39 genes with distinctive, restricted VH and VK CDR3 sequences.22,23 Subset #8 displays a signifi cant enrichment for trisomy 12 and NOTCH1 mutations, offering yet another example of subset-biased profi les of genomic aberrations.11-13,15 In the original report of subset #8 it was noted that 2 of 5 patients belonging to subset #8 experienced Richter’s transformation.22 This initial observation was subsequently corroborated by a collaborative study from Italy reporting that patients belonging to subset #8 had a 10-fold higher risk for this development compared to all other patients with CLL.17 Subsequently, the meta-analysis of 3 prospective clinical trials conducted by the German CLL Study Group showed that patients belonging to subset #8 experienced the highest risk of Richter’s transformation, albeit the incidence was lower.16 On these grounds, ERIC, the European Research Initiative on CLL, recommends closer follow-up and a lower threshold for a fl uorodeoxyglucose positron emission tomography (PET)/ CT guided biopsy for subset #8 patients experiencing evidence of disease progression (also under therapy) in order to exclude the possibility of Richter’s transformation.24
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Journal:  Molecular pathways in glioblastoma-derived stem cells to identify effective drug agents: A bioinformatics study. (Pubmed Central) -  Sep 21, 2022   
    Chlorambucil, cyclosporine A, doxorubicin, and etoposide were selected as the drug agents. Using integrated bioinformatics analyses, it was found that prominent genes in the cell cycle and cytoskeletal pathways are more expressed in cancer stem cells and that Chlorambucil, cyclosporine A, doxorubicin, and etoposide can be effective compounds to attenuate these cells.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Journal:  Antitumor effects of pyrrole-imidazole polyamide modified with alkylating agent on prostate cancer cells. (Pubmed Central) -  Aug 24, 2022   
    In the present study, we developed a PIP modified with a DNA alkylating agent, chlorambucil (ChB) (OCT1-PIP-ChB)...Importantly, in vivo study using 22Rv1 xenografts, we showed that OCT1-PIP-ChB significantly reduced tumor growth compared to the control group without showing obvious adverse effects. Thus, the PIP combined with ChB can exert a significant inhibitory effect on prostate cancer cell proliferation and castration-resistant tumor growth, suggesting a potential role as a therapeutic agent.
  • ||||||||||  Mustargen (mechlorethamine) / Recordati, Leukeran (chlorambucil) / GSK
    Reactive oxygen species (ROS) mediated prodrugs: mechanism and combination strategy. | Poster Board #2307 (Hall F2 (McCormick Place Convention Center)) -  Aug 9, 2022 - Abstract #ACSFall2022ACS_Fall_2823;    
    Nitrogen mustard containing compound are known well-known for their high reactivity towards different types of cancers...Compound FAN-NM-CH3 was 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...In this work, we measure extracellular H2O2 production level in MDA-MB-468 cells, evaluate effects of ROS quencher/enhancer on prodrug toxicity to define correlation between H2O2 level and efficacy. Additionally understand drug’s mechanism of action as a DNA alkylating agent through evaluation of gene expression.