Leukeran (chlorambucil) News

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|||||||||| Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
PROGNOSTIC SIGNIFICANCE OF CHRONIC LYMPHOCYTIC LEUKEMIA WITH IGHV-U IN THE ERA OF NOVEL AGNETS; REAL-L?FE DATA () - May 12, 2023 - Abstract #EHA2023EHA_3333;
Our real life data suggested novel agents targeting B-cell receptor (BCR) pathway kinases or BCL-2 inhibitors can overcome the poor prognosis associated with unmutated IGHV status . Immunoglobulin gene, Chronic lymphocytic leukemia

|||||||||| CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): REAL-WORLD DATA FROM LEBANON () - May 12, 2023 - Abstract #EHA2023EHA_3326;
CLL survival in Lebanon is in accordance with international standards in the literature. Survival, Real world data, Chronic lymphocytic leukemia

|||||||||| Calquence (acalabrutinib) / AstraZeneca
NAOS STUDY: FIRST INTERIM ANALYSIS OF ACALABRUTINIB USE IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA IN A REAL-LIFE SETTING. () - May 12, 2023 - Abstract #EHA2023EHA_3303;
In this first analysis, most patients received acalabrutinib as first-line therapy. Acalabrutinib was used in patients older than in the published phase III clinical trials, with more frailties (ECOG, creatinine clearance) and cardiovascular risks.

|||||||||| IS CHEMOIMMUNOTHERAPY (CIT) HISTORY IN THE FIRST LINE TREATMENT OF CHRONIC LYMPHOCYTIC LEUKAEMIA? () - May 12, 2023 - Abstract #EHA2023EHA_3299;
This concept should be validated from multi-centric data and possibly tested in prospective trials. B-CLL

|||||||||| REAL-WORLD TREATMENT AND OUTCOMES OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) RECEIVING FIRST-LINE (1L) THERAPY IN THE NOVEL AGENT ERA: AN INTERNATIONAL STUDY (Poster area) - May 12, 2023 - Abstract #EHA2023EHA_2247;
We observed that almost 50% of pts were treated in the front-line setting with anti-CD20 monotherapy or CT/CIT despite availability of targeted agents. The continued use of anti-CD20 monotherapy and CT/CIT is surprising in the era of novel agents.

|||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Imbruvica (ibrutinib) / AbbVie, J&J
GENETIC ALTERATIONS AND OUTCOMES WITH FIXED-DURATION IBRUTINIB+VENETOCLAX (IBR+VEN): RESULTS FROM THE PHASE 3 GLOW STUDY IN PATIENTS WITH PREVIOUSLY UNTREATED CLL (Poster area) - May 12, 2023 - Abstract #EHA2023EHA_2243;
PFS in pts treated with Ibr+Ven was significantly improved vs Clb+O across most genomic subgroups, including mIGHV and uIGHV. Presence of +12 trended in favor of Ibr+Ven that was NS.

|||||||||| 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

|||||||||| Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
EXTENDED LOW DOSE RITUXIMAB REGIMEN FOR THE TREATMENT OF ADULT PATIENTS WITH STEROID-DEPENDENT AND FREQUENTLY RELAPSING MINIMAL CHANGE DISEASE (Focussed Oral Room 9) - May 4, 2023 - Abstract #ERAEDTA2023ERA_EDTA_1849;
This regimen allows minimization exposure to rituximab as well as disease remission during a longer period of time.Figure 1. Box plot of the number of nephrotic syndrome relapses during the two yearsperiod before and after rituximab administration in the study group.

|||||||||| 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
Gold standard: I recall in CLL, chlorambucil was often used as the sub-optimal comparator for many many trials. Regulators equally responsible for letting this happen as well as industry. I do believe things have tightened up now and serious research requires a gold standard SOC control arm (Twitter) - Apr 22, 2023

|||||||||| 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, Sutent (sunitinib) / Pfizer
Clinical: This is one of my major pet peeves. We have four different category 1 combos for Renal Cell Carcinoma and have no idea which is better. Most were approved compared to Sunitinib which hasn't been standard first line therapy in years. Same with CLL trials using chlorambucil. (Twitter) - Mar 29, 2023

|||||||||| 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.

|||||||||| Leukeran (chlorambucil) / GSK, pomalidomide / Generic mfg.
Clinical: You bring up a great point Weak comparitor arms in registration trials Eg- pom/Dex in MM Chlorambucil based in CLL Placebo vs low dose Tam in DCIS when full dose Tam has been SOC for yrs Chemo vs Chemo + "new " I/O in met lung when Chemo I/o is SOC List goes on #MedTwitter (Twitter) - Mar 19, 2023

||||||||||  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,  Sponsor: AstraZeneca
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

||||||||||  Imbruvica (ibrutinib) / AbbVie, J&J
Trial completion date, Trial primary completion date:  Open-label Extension Study in Patients 65 Years or Older With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (clinicaltrials.gov) -  Feb 28, 2023
P3, N=232, Active, not recruiting,  Sponsor: Pharmacyclics LLC.
This protocol provides a reference Trial completion date: Apr 2023 --> Jul 2023 | Trial primary completion date: Apr 2023 --> Jul 2023

|||||||||| 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.

|||||||||| Leukeran (chlorambucil) / GSK, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Genuine question !! Why is the control arm of the GLOW trial, Chlorambucil + Obinutuzumab ?? The study start date is April 2018. #MedTwitter @NitinJainMD @NicoGagelmann @BijoyTelivala (Twitter) - Feb 24, 2023

|||||||||| Leukeran (chlorambucil) / GSK
Analysis of nonenzymatic glutathione conjugate formation of chemotherapy agents cyclophosphamide and chlorambucil, using NMR spectroscopy (Hall F-H (Indiana Convention Center)) - Feb 14, 2023 - Abstract #ACSSp2023ACS_SP_4798;
Our findings did show a new peak in the NMR, but TLC and mass spectrometry data was inconclusive. Further research will be required to elucidate the structure of the unknown compound.

|||||||||| 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: Pharmacological tumor PDL1 depletion with chlorambucil treats ovarian cancer and melanoma: improves antitumor immunity and renders anti-PDL1-resistant tumors anti-PDL1-sensitive through NK cell effects. (Pubmed Central) - Feb 9, 2023
Pharmacological tumor PDL1 depletion with chlorambucil targets tumor-intrinsic PDL1 signaling that mediates treatment resistance, especially in ?PDL1-resistant tumors, generates PDL1-dependent tumor immunogenicity and inhibits tumor growth in immune-dependent and independent manners. It could improve treatment efficacy of selected agents in otherwise treatment-refractory, including ?PDL1-refractory cancers, and is rapidly clinically translatable.

|||||||||| Leukeran (chlorambucil) / GSK, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Journal: Antibodies Produced by CLL Phenotype B Cells in Patients With Myasthenia Gravis Are Not Directed Against Neuromuscular Endplates. (Pubmed Central) - Feb 8, 2023
It could improve treatment efficacy of selected agents in otherwise treatment-refractory, including ?PDL1-refractory cancers, and is rapidly clinically translatable. Our study suggests that AChR autoantibodies are produced by nonmalignant, polyclonal B cells The new anti-CD20 treatment obinutuzumab might be considered in effectively treating AChR MG.

|||||||||| Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche, Calquence (acalabrutinib) / AstraZeneca
Not to forget Chemoimmuotherapy. Let it be R-CHOP or B+R and start Acalabrutinib post initial control. If progressing, counsel and even give an option of Chlorambucil Palliation or if fit enough salvage more till the point of Transplant. Rest all theory for now in India. (Twitter) - Feb 4, 2023

|||||||||| 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.

|||||||||| ibrutinib / Generic mfg.
Clinical data, Journal: Characteristics and Clinical Outcomes of Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Receiving Ibrutinib for ≥5 Years in the RESONATE-2 Study. (Pubmed Central) - Jan 22, 2023
More than half (58%) of ibrutinib-randomized patients benefitted from ibrutinib treatment for ≥5 years regardless of baseline characteristics. Dose modification resolved AEs for most patients, thereby facilitating continued treatment.

|||||||||| In EU with benda approved only en LF, but not funded for this indication in NHS. For LLC approved (and funded) with Venetoclax and Chlorambucil With Benda o fludarabine Rituximab (Twitter) - Jan 19, 2023

|||||||||| ibrutinib / Generic mfg.
Review, Journal: Many People With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Benefit From Ibrutinib Treatment Up To 8 Years: A Plain Language Summary. (Pubmed Central) - Jan 10, 2023
P3
In people with CLL or SLL, more participants who were taking ibrutinib were alive without worsening of their disease after 7 years compared with participants who took chlorambucil. Clinical Trial Registration: NCT01722487 (ClinicalTrials.gov) Clinical Trial Registration: NCT01724346 (ClinicalTrials.gov).

||||||||||  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,  Sponsor: Acerta Pharma BV
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
Clinical: If you paid people "a lot" to participate in cancer studies, you would just be punishing people who need the money to participate in unethical trials like ASCENT, like VISION, like POLO. It would be sick and twisted. People randomized to chlorambucil & decarbazine. Horrible (Twitter) - Jan 3, 2023

|||||||||| Leukeran (chlorambucil) / GSK, Sutent (sunitinib) / Pfizer
Clinical: If you don’t prescribe the drug of protocol for a pt , don’t put the pt on a trial where that drug is given in comparator arm Ex - Chlorambucil in CLL Sutent in RCC #MedTwitter #clinicaltrials (Twitter) - Dec 24, 2022

|||||||||| Leukeran (chlorambucil) / GSK, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Journal: Obinutuzumab plus chlorambucil versus ibrutinib in previously untreated chronic lymphocytic leukemia patients without TP53 disruptions: A real-life CLL campus study. (Pubmed Central) - Dec 9, 2022
Hematological toxicities were common in the G-CHL arm, while IB was associated with higher costs. Although continuous IB provides better disease control in CLL, IGHV mutated patients and those achieving an undetectable MRD show a marked clinical and economic benefit from a fixed-duration obinutuzumab-based treatment.

|||||||||| 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.

|||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Calquence (acalabrutinib) / AstraZeneca
Acalabrutinib ± Obinutuzumab vs Obinutuzumab + Chlorambucil in Treatment-Naive Chronic Lymphocytic Leukemia: 5-Year Follow-Up of ELEVATE-TN () - Nov 30, 2022 - Abstract #DKK2022DKK_1920;
P3
After a 5-y follow-up, efficacy and safety of A+O and A monotherapy were maintained, with significantly longer OS in the A+O arm compared with O+Clb. Sponsor: Acerta Pharma BV; AstraZeneca

|||||||||| 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.

|||||||||| Mustargen (mechlorethamine) / Recordati
Journal: Novel nitrogen mustard-artemisinin hybrids with potent anti-leukemia action through DNA damage and activation of GPx. (Pubmed Central) - Nov 22, 2022
Preliminary studies showed that nitrogen mustard exerted an efficient effect, and 5a can combine the advantages of artemisinin and nitrogen mustard and exhibit effects superior to either. This study showed that 5a should be further investigated as a therapeutic compound against leukemia.

|||||||||| Leukeran (chlorambucil) / GSK
Journal: Core-Coordinated Elliptic Polymer Nanoparticles Loading Copper(II) and Chlorambucil for Cooperative Chemodynamic/Chemotherapy. (Pubmed Central) - Nov 16, 2022
Additionally, the disulfide bond endows GSH-responsive CBL release and provokes further GSH decline, finally realizing combined CDT/CT toward enhancing antitumor outcomes, and in vitro as well as in vivo studies indeed reveal remarkable efficacy. Such a system can provide valuable advantages to create novel nanomedicines toward cascade antitumor therapy.

|||||||||| Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Observational data, Journal: Rituximab or rituximab plus chlorambucil for translocation (11;18)-negative gastric mucosa-associated lymphoid tissue lymphoma: a monocentric non-randomized observational study. (Pubmed Central) - Nov 15, 2022
Combination therapy may be a preferable choice in patients with gastric MALT lymphoma irrespective of t(11;18) status. Further studies should assess benefit of stopping chlorambucil in early good-responder patients.

|||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Journal, HEOR: A Probabilistic Cost-Effectiveness Analysis of Venetoclax and Obinutuzumab as a First-Line Therapy in Chronic Lymphocytic Leukemia in Canada. (Pubmed Central) - Nov 6, 2022
Further studies should assess benefit of stopping chlorambucil in early good-responder patients. VEN+O is a cost-effective treatment option for unfit frontline CLL patients and provides value for money to healthcare payers.



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