Leukeran (chlorambucil) / GSK 
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  • ||||||||||  Calquence (acalabrutinib) / AstraZeneca
    Clinical, Review, Journal:  The role of acalabrutinib in adults with chronic lymphocytic leukemia. (Pubmed Central) -  Feb 23, 2021   
    Ibrutinib was the first-in-class drug which was initially approved by the US Food and Drug Administration (FDA) for the treatment of patients with relapsed/refractory and later for patients with treatment-naïve CLL...The ELEVATE TN trial investigated acalabrutinib with or without obintuzumab versus chlorambucil-obinutuzumab in older and frail patients with previously untreated CLL...Both trials demonstrated superiority of the acalabrutinib-containing arms in terms of both efficacy and tolerability. Unfortunately, the availability of new generation BTK inhibitors has not resulted in mitigating the financial toxicities associated with these potentially life-long treatments.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Journal:  Regulating mitochondrial pH with light and implications for chemoresistance. (Pubmed Central) -  Feb 18, 2021   
    Specific assays indicated that BD-PAG is capable of regulating mitochondrial pH with significant effects on mitochondrial membrane depolarization. Therapeutic tests using chlorambucil in combination with BD-PAG revealed a new strategy in chemoresistance suppression.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Journal:  DNA alkylation of the RUNX-binding sequence by CBI-PI polyamide comjugates. (Pubmed Central) -  Feb 11, 2021   
    Chb-M' was developed by conjugating pyrrole-imidazole (PI) polyamides and chlorambucil as an anticancer agent...In this study, to explore the possibility of an alternative structure, we designed a new series of CBI-PI polyamides, in which seco-CBI was applied as a DNA-alkylating agent. We examined the characteristics of the CBI-PI polyamides targeting the RUNX-binding sequence and found that these conjugates have great potential for cancer treatment.
  • ||||||||||  Yinuokai (orelabrutinib) / InnoCare, Biogen
    Enrollment open:  ICP-022 Versus Chlorambucil Combined With Rituximab in the Treatment of Untreated CLL/SLL (clinicaltrials.gov) -  Feb 10, 2021   
    P3,  N=218, Recruiting, 
    We examined the characteristics of the CBI-PI polyamides targeting the RUNX-binding sequence and found that these conjugates have great potential for cancer treatment. Not yet recruiting --> Recruiting
  • ||||||||||  Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
    Journal, IO biomarker:  Current diagnosis and treatment of chronic lymphocytic leukaemia (Pubmed Central) -  Feb 2, 2021   
    This combination was shown to be clearly superior to chlorambucil/obinutuzumab and should become the preferred first-line treatment for the so called "slow-go" patients...In addition to disease-related factors (e. g. presence of deletion 17p/TP53 mutation, IgHV mutational status, prior therapies), comorbidities, co-medication and the specific side effects of the CLL therapies (myelosuppression, infections and secondary malignancies for chemoimmunotherapy; cardiac toxicity, bleeding and autoimmune disease for ibrutinib; tumour-lysis syndromes and infections for venetoclax) the patient's expectations need to be considered.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Journal:  Low-Power Near-Infrared-Responsive Upconversion Nanovectors. (Pubmed Central) -  Feb 2, 2021   
    By using 3-perylenecarboxaldehyde, Tm/Yb ion-doped UCNP-containing isocyanides, and antitumor agent chlorambucil as the three components, the resulting monodisperse UCPNV exhibits an efficient release of caged chlorambucil under a very low 976 nm power. This approach expands the synthetic toolbox to enable quick development of UCPNVs for UCNP-assisted low-power NIR photochemistry.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    [VIRTUAL] Chronic Lymphocytic Leukemia: Molecular Diagnostics, Epigenetics, and New Treatments () -  Jan 22, 2021 - Abstract #VLML2021VLML_73;    
    Objective The aim of the study was to assess the effect of chlorambucil (CLB) and valproic acid (VPA) used separately and in combination on the viability and apoptosis of CLL cells in vitro...Results The combination of presented drugs showed ability to induce apoptosis effect in CLL cells, and potentially to reduce the toxicity of the treatment. Conclusion The present study strongly suggests further investigations on CLB and VPA combination in CLL treatment.
  • ||||||||||  dexamethasone / Generic mfg.
    [VIRTUAL] ACQUIRED COAGULOPATHY AS A PRIMARY MANIFESTATION OF HEMATOLOGICAL MALIGNANCIES: TWO CASE REPORTS () -  Jan 8, 2021 - Abstract #EAHAD2021EAHAD_223;    
    If an acquired factor inhibitor is confirmed patients should be managed jointly with a Haemophilia Centre experienced in the management of inhibitors. Haemostatic therapy depends on the specificity of the inhibitor and the improvement of the acquired abnormality may lack behind hematologic response requiring a longer follow‐up.
  • ||||||||||  Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
    [VIRTUAL] Real world outcomes for treatment of diffuse large B cell Lymphoma in patients aged 80 and over () -  Jan 5, 2021 - Abstract #BSHI2020BSH-I_340;    
    The median OS of 33 months for patients treated with curative intent is similar to 29 months reported previously by the GELA group for R‐miniCHOP in patients aged over 80. However only 50% of this age group were felt to be fit enough to receive this treatment in our cohort and the survival for those treated palliatively was short indicating an unmet need for effective well‐tolerated treatment in this group.
  • ||||||||||  Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
    [VIRTUAL] Treatment decisions in Waldenstrom's Macroglobulinaemia; outcomes from the South East Scotland Cancer Network () -  Jan 5, 2021 - Abstract #BSHI2020BSH-I_320;    
    Alternative frontline regimens included R‐CVP (n = 4), R‐CHOP (n = 1) and R‐Bendamustine (n = 1)...Two patients had Bing‐Neel Syndrome and the third was frail and relapsed following first line Rituximab and Chlorambucil...Indeed, some unfit patients declined chemoimmunotherapy or were offered symptomatic management only. It is clear that many of these patients may have benefited from Ibrutinib and there will no doubt be an increase in Ibrutinib use going forward in this patient group.
  • ||||||||||  Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
    [VIRTUAL] Real‐world treatment patterns, adverse events and clinical outcomes in patients with chronic lymphocytic leukaemia treated with ibrutinib in the United Kingdom () -  Jan 5, 2021 - Abstract #BSHI2020BSH-I_273;    
    Other therapies received included the combination of fludarabine, cyclophosphamide and rituximab (first‐line, 24·3%), bendamustine plus rituximab (first‐line, 20·9%; second‐line, 13·5%) and chlorambucil plus rituximab (first‐line, 8·5%). Overall, the median progression‐free survival was 28·7 months and median overall survival was not reached...Among patients who initiated further therapy following discontinuation of first‐ or second‐line ibrutinib (n = 13), venetoclax was the most common therapy (53·8%)...The majority of ibrutinib use was in the second‐line or later. AEs such as bruising and cytopenias were commonly reported in patients treated with ibrutinib.
  • ||||||||||  Actemra IV (tocilizumab) / Roche, JW Pharma
    [VIRTUAL] Experiences of providing commercial Chimeric Antigen Receptor (CAR‐T) cell therapy at the Northern Centre for Cancer Care () -  Jan 5, 2021 - Abstract #BSHI2020BSH-I_19;    
    Six (40%) received steroids (in all cases this was IV dexamethasone) for issues related directly to CAR‐T therapy...Four patients (29% of cohort available to follow‐up) have died after CAR‐T infusion. Progression‐free survival rates as calculated at standardised follow‐up points were 71% at 28 days, 31% at 3 months, and 27% at 6 months after CAR‐T infusion. One patient who had initial disease progression later had a subsequent complete response after receiving another line of treatment.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Journal:  Hybrid inhibitors of DNA and HDACs remarkably enhance cytotoxicity in leukaemia cells. (Pubmed Central) -  Jan 2, 2021   
    Chlorambucil is a nitrogen mustard-based DNA alkylating drug, which is widely used as a front-line treatment of chronic lymphocytic leukaemia (CLL)...The mechanism behind its remarkably enhanced cytotoxicity is that chloram-HDi not only causes a significant DNA damage of leukaemia cells but also downregulates DNA repair protein, Rad52, resulting in the escalation of its DNA-damaging effect. Furthermore, chloram-HDi inhibits HDAC enzymes to induce the acetylation of α-tubulin and histone H3.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Journal:  Intra- and inter-laboratory reproducibility of the rat blood Pig-a gene mutation assay. (Pubmed Central) -  Dec 20, 2020   
    Dunnett's test results showed similar qualitative outcomes within and between laboratories, that is, each chemical and each study demonstrated statistically significant, dose-related increases in mutant reticulocyte and erythrocyte frequencies. Benchmark dose analysis (PROAST software) provided a means to quantitatively analyze the results, and the relatively tight, overlapping benchmark dose confidence intervals observed for each of the two chemicals indicate that within and between laboratory reproducibility of the Pig-a assay are high, adding further support for the development of an OECD test guideline.
  • ||||||||||  Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
    Clinical, Journal:  Rapid cognitive decline in a patient with chronic lymphocytic leukaemia: a case report. (Pubmed Central) -  Dec 1, 2020   
    Nevertheless, clinicians should maintain a certain level of suspicion for this risk, especially in the context of patients presenting with clinical syndromes of encephalopathy and focal neurologic deficits. Furthermore, research to better our understanding of the manifold links between B-cell function and JCV regulation could provide valuable information for use in the future prevention and treatment of PML.
  • ||||||||||  Campath (alemtuzumab) / Sanofi, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
    [VIRTUAL] Clinical Characteristics and Outcomes of Newly Diagnosed Patients with Chronic Lymphocytic Leukemia Who Are 80 Years of Age or Older () -  Nov 5, 2020 - Abstract #ASH2020ASH_5260;    
    Frontline novel agent treatments included ibrutinib alone (n=1), acalabrutinib alone (n=1), and ibrutinib, obinutuzumab, venetoclax (n=1)...Although survival outcomes did not differ by era across the 25-year span of this study, pts treated with novel agents were underrepresented and are a patient population which warrants additional evaluation. The finding that pts with CLL in this cohort had a 20% higher risk of death compared to an age- and sex-matched population emphasize the need for ongoing efforts to improve clinical outcomes for CLL pts in this demographic category.
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie, Leukeran (chlorambucil) / GSK
    [VIRTUAL] Establishment ofin VitroDrug Sensitivity Screening Assay for Chronic Lymphocytic Leukemia (CLL) Primary Patient Samples () -  Nov 5, 2020 - Abstract #ASH2020ASH_5137;    
    In addition to drug response, whole exome sequencing and RNAseq are being conducted on these samples, to compare mutational analyses with drug responsiveness. With clinically annotated patient-derived CLL samples, WES and RNAseq plus drug response to standard of care provides a comprehensiveex vivoplatform for the preclinical testing of drug candidates, which may not only provide information on agent efficacy, but that can permit potential biomarker mining and exploration of patient selection criteria for investigational new agents in CLL.
  • ||||||||||  tacrolimus / Generic mfg.
    [VIRTUAL] RUNX-NFAT Axis As a Novel Therapeutic Target for AML and T Cell Immunity (Poster Hall (Virtual Meeting)) -  Nov 5, 2020 - Abstract #ASH2020ASH_3674;    
    As immunosuppressive approach for the prevention or treatment of aGVHD, calcineurin inhibitors, cyclosporine A and tacrolimus, inhibit GVHD by preventing the activation of NFAT, and steroid inhibits transcription of proinflammatory genes...Finally, to achieve “cluster regulation of RUNX (CROX)” strategy, we have been developing a novel RUNX inhibitor: chlorambucil-conjugated pyrrole-imidazole (PI) polyamides (Chb-M’) that targets consensus RUNX-binding sequences, and specifically inhibits binding of RUNX family members...Chb-M’ also suppressed NFATC2 and cytokine gene expression in peripheral blood mononuclear cells (PBMC) and ameliorated GVHD for xenogeneic GVHD mouse model by transplanting human PBMC into immunodeficient mice. Taken together, we show RUNX could be a novel therapeutic target against diverse AML and GVHD through targeting RUNX-NFAT axis.
  • ||||||||||  Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
    [VIRTUAL] Relative Survival of Patients with Nodal Marginal Zone Lymphoma in the United States: A Population-Based Analysis (Poster Hall (Virtual Meeting)) -  Nov 5, 2020 - Abstract #ASH2020ASH_3015;    
    There has been a significant improvement in RS in the most recent era for patients with NMZL in the United States after adjusting for differences in age, sex, race/ethnicity, income, and stage at diagnosis. This improvement at the population level is likely reflective of the improvement in supportive care and advances in the NMZL treatment including identification of better tolerable chemotherapy regimens and novel agents.