- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Zarzio (filgrastim biosimilar) / Novartis, Gazyva (obinutuzumab) / Roche, Biogen
[VIRTUAL] VENETOCLAX-OBINUTUZUMAB MODULATES CLONAL GROWTH: RESULTS OF A POPULATION-BASED MINIMAL RESIDUAL DISEASE MODEL FROM THE RANDOMIZED CLL14 STUDY () - May 13, 2021 - Abstract #EHA2021EHA_1248; Aims The aim of this report is to provide a population-based exploratory analysis of MRD growth dynamics after stopping Ven-Obi and chlorambucil-Obi (Clb) therapy and to compare growth trajectories between targeted treatment versus chemoimmunotherapy...Conclusion This analysis establishes a robust, population-based model of MRD growth dynamics that allows description of growth trajectories and treatment effects after treatment cessation. In addition to more effective MRD eradication with Ven-Obi, our results demonstrate that MRD growth is modulated more efficiently by BCL2-targeting treatment in contrast to genotoxic chemoimmunotherapy.
- |||||||||| Zarzio (filgrastim biosimilar) / Novartis
[VIRTUAL] OTHER MALIGNANCIES IN THE HISTORY OF CHRONIC LYMPHOCYTIC LEUKEMIA – A RETROSPECTIVE, MULTICENTER COHORT STUDY BY ERIC, THE EUROPEAN RESEARCH INITIATIVE ON CLL, IN HARMONY () - May 13, 2021 - Abstract #EHA2021EHA_1247; Frontline therapies were FCR (32.3% of cases), bendamustine+/-antiCD20 (10.7%), other CIT (mostly chlorambucil+antiCD20) (46.7%), BTKi+/-combinations (4.8%), idelalisib+/-combinations (0.5%), venetoclax+/-combinations (0.9%), various other regimens (4%)...Conclusion We report strong associations between the development of other hematological malignancies, especially MDS/AML, and certain biological features as well as treatment for CLL, with a highly relevant risk for patients treated with CIT, particularly the FCR regimen. In contrast, the development of solid tumors appeared unaffected by treatment administration, prompting further investigation in specific patient subgroups that will be presented at the congress.
- |||||||||| Zarzio (filgrastim biosimilar) / Novartis
[VIRTUAL] DOES INTENSIVE CHEMOTHERAPY REALLY HELP OLDER DLBCL PATIENTS LIVE LONGER? () - May 13, 2021 - Abstract #EHA2021EHA_1099; Four treatment groups were included for analyses: intensive chemotherapy (full dose RCHOP/RGCVP/R-PMitCEBO, N=53); reduced-intensity chemotherapy (R-miniCHOP/RCVP, N=32); palliative chemotherapy (VEDEX/Chlorambucil/Etoposide, N=21) and palliative without chemotherapy (steroids/palliative radiotherapy, N=67)...This may be due to the elderly population having difficulty tolerating intensive chemotherapy leading to treatment ‘holidays’, an overall decline in health and a lower OS than reduced-intensity chemotherapy - it is therefore highlighted here as a potential point of future research. Better powered analyses should further examine patient factors such as treatment tolerability, complication rates and late effects which may impact on OS in this frail study population.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen
[VIRTUAL] VENETOCLAX-OBINUTUZUMAB FOR PREVIOUSLY UNTREATED CHRONIC LYMPHOCYTIC LEUKEMIA: 4-YEAR FOLLOW-UP ANALYSIS OF THE RANDOMIZED CLL14 STUDY () - May 13, 2021 - Abstract #EHA2021EHA_524; P3 Background The CLL14 study showed significant improvement of progression-free survival (PFS) with venetoclax-obinutuzumab (Ven-Obi) as compared to chlorambucil-obinutuzumab (Clb-Obi) in patients (pts) with previously untreated chronic lymphocytic leukemia (CLL) and coexisting conditions...The majority of pts remains without relapse three years after completing Ven-Obi treatment. Although adverse features such as TP53 mutation/deletion were not fully mitigated, fixed-duration Ven-Obi continues to be an effective treatment for all pts with CLL and with coexisting conditions.
- |||||||||| Leukeran (chlorambucil) / GSK, Gazyva (obinutuzumab) / Roche, Biogen
[VIRTUAL] Immunotactoid Glomerulonephritis in a donor kidney () - May 12, 2021 - Abstract #BSH2021BSH_438; We suggest when dealing with Immunotactoid Glomerulopa- thy, consider early evaluation for Lymphoproliferative disorder. Correct diagnosis in a timely manner led to the salvage of the trans- plant kidney.
- |||||||||| Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
[VIRTUAL] How does survival differ by treatment route in elderly DLBCL? () - May 12, 2021 - Abstract #BSH2021BSH_434; This study also shows that it may be reasonable not to burden patients with tablet chemotherapy when choosing between oral and palliative options but better-powered analyses are required. Additionally, we show that whilst intravenous therapies lead to a longer OS, it is not clear to what extent this is due to its superiority as a treatment or because of a bias wherein it is selec- tively offered to patients with a better outlook – this is an area for further research.
- |||||||||| Calquence (acalabrutinib) / AstraZeneca
[VIRTUAL] Acalabrutinib-related cardiac toxicities in patients with chronic lymphocytic leukaemia: a meta-analysis of randomised controlled trials () - May 12, 2021 - Abstract #BSH2021BSH_247; Abstract Content: Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia, Acalabrutinib, a second generation and more selective Bruton’s tyrosine kinase inhibitor, was developed to potentiate efficacy while minimizing ibrutinib-associated side effects...Studies compared acalabrutinib + obinutuzumab versus acalabrutinib monotherapy versus obinutuzumab + chlorambucil in ELEVATE TN trial and acalabrutinib versus investigator’s choice chemotherapy (idelalisib + rituximab or bendamustine + rituximab) in ASCEND trial...There was no significant increase in the risk of all grades of hypertension and high-grade cardiac events or AF in the acalabrutinib group. Future prospective studies are necessary to determine the potential risk factors to develop cardiac toxicities in patients with CLL who received acalabrutinib.
- |||||||||| [VIRTUAL] Towards control of chronic lymphocytic leukemia with targeted agents (Channel 1) - May 8, 2021 - Abstract #ICML2021ICML_220;
Very encouraging results have also been reported recently regarding the combination of venetoclax plus ibrutinib.48,49 Future prospects: We have entered a new era where combinations of targeted agents achieve long-lasting remissions for the majority of CLL patients...CLL17 protocol of the German CLL Study Group Moreover, we need to intensify our effort to understand and neutralize the cellular mechanism of resistance to the new inhibitors. Finally, and most importantly, we need to make sure that these novel therapies will become available to all patients with CLL world-wide.
- |||||||||| Leukeran (chlorambucil) / GSK
Journal: Phytochemical Fingerprinting and Activity of Extracts from the Leaves of Dolichos kilimandscharicus (Fabaceae) on Jurkat-T Cells. (Pubmed Central) - May 6, 2021 The extracts were tested with increasing concentration, using chlorambucil as a standard anticancer drug...The results of this study showed that the ethanol and ethyl acetate leaf extracts of D. kilimandscharicus have antiproliferative activity against Jurkat-T cells and may act by inducing apoptosis.. The current findings offer supporting evidence for the use of these plant species in the treatment of cancer in ethnomedicinal practices.
- |||||||||| Leukeran (chlorambucil) / GSK
Journal, PARP Biomarker: HuR Affects Proliferation and Apoptosis of Chronic Lymphocytic Leukemia Cells via NF-κB Pathway. (Pubmed Central) - Apr 29, 2021 HuR may be a key protein regulating CLL resistance. After inhibiting HuR, inflammatory response and apoptosis were significantly increased, and the cell sensitivity to CLB and Flu increased, suggesting that inhibiting HuR activity may be a potential strategy to solve the problem of drug resistance in CLL cells.
- |||||||||| lithium carbonate ER / Generic mfg., irinotecan / Generic mfg.
Journal: The use of a Gene Expression Signature and Connectivity Map to repurpose drugs for Bipolar Disorder. (Pubmed Central) - Apr 28, 2021 With a median follow-up of 46.9 mo (̃4y), the efficacy and safety of A+O and A monotherapy was maintained, with an increase in CR since the interim analysis (from 21% to 27% [A+O] and from 7% to 11% [A]) and low rates of discontinuation. This study shows that GES and CMap can be used as tools to repurpose drugs for BD.
- |||||||||| Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Clinical, Journal, IO biomarker: IGHV mutational status and outcome for patients with chronic lymphocytic leukemia upon treatment: a Danish nationwide population-based study. (Pubmed Central) - Apr 28, 2021 Thus, it appears that patients progressing after intensive chemoimmunotherapy as first line therapy can be rescued by subsequent treatment, without jeopardizing long overall survival, in the real-world setting. Intensive chemoimmunotherapy remains a legitimate option alongside targeted agents, and part of a personalized treatment landscape in chronic lymphocytic leukemia, while improved supportive care and treatment options are warranted for unfit patients.
- |||||||||| Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Clinical, Journal: Early progression of disease predicts shorter survival in MALT lymphoma patients receiving systemic treatment. (Pubmed Central) - Apr 28, 2021 This prognostic impact was confirmed in the validation set, in which early POD was observed in 64 out of 224 (29%) evaluable patients with 10-year OS rate of 48% in the early POD group and 71% in the reference group (HR= 2.15, 95%CI, 1.19-3.90; log-rank P=0.009). In patients with EMZL who received front-line systemic treatment, early POD is associated with poorer survival and may represent a useful endpoint in future prospective clinical trials.
- |||||||||| cyclosporine / Generic mfg.
[VIRTUAL] Cryosurgery as a novel treatment for Sweet Syndrome: A case report () - Apr 10, 2021 - Abstract #AADVMX2021AAD_VMX_206; However, to our knowledge, no known reports have been published suggesting cryosurgery as a treatment option. Additional patient history possibly contributing to the recurrent Sweet Syndrome include a history of breast cancer, recurrent Pseudomonal infections, and diabetes mellitus type two.
- |||||||||| Arzerra (ofatumumab) / Novartis, Genmab
Review, Journal: The evolving role of Bruton's tyrosine kinase inhibitors in chronic lymphocytic leukemia. (Pubmed Central) - Apr 7, 2021 P3 Similarly, the Alliance trial demonstrated the superiority of ibrutinib over bendamustine with rituximab as frontline in elderly patients...The ELEVATE TN trial demonstrated the superiority of acalabrutinib with or without obinutuzumab over chlorambucil and obinutuzumab as frontline therapy for elderly or comorbid patients...The ongoing phase III GAIA/CLL13, ECOG EA9161, Alliance A041702, CLL17, and [ClinicalTrials.gov identifier: NCT03836261] trials will assess various combinations of ibrutinib/acalabrutinib, venetoclax, and anti-CD20 antibodies...Can undetectable MRD be used to determine treatment duration? In this review, we will discuss these and other aspects of the evolving role of BTK inhibition in CLL.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Leukeran (chlorambucil) / GSK, Zydelig (idelalisib) / Gilead
[VIRTUAL] In vitro drug sensitivity screening platform for primary chronic lymphocytic leukemia (CLL) patient samples. () - Mar 13, 2021 - Abstract #AACR2021AACR_4160; 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 comprehensive ex vivo platform 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.
- |||||||||| Leukeran (chlorambucil) / GSK
Journal, Combination therapy: Targeted photoresponsive carbazole-coumarin and drug conjugates for efficient combination therapy in leukemia cancer cells. (Pubmed Central) - Mar 9, 2021 The present study investigated the synthesis and efficacy of carbazole-coumarin (CC)-fused heterocycles as a PTDDS platform for the photocontrolled release of a chemotherapeutic agent, chlorambucil, in an in vitro model of human breast and leukemia cancer cells...Further, the lower IC of CC-8 toward leukemia cells suggests the efficacy of the TPP ligand in increasing the bioavailability of CC-drug conjugates in leukemia treatment. Studies on mitochondria-targeting drug delivery systems are required for improving the performance of anticancer drugs.
- |||||||||| Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
[VIRTUAL] IgA Nephropathy associated with Psoriasis and Lymphoma () - Mar 2, 2021 - Abstract #NKFSCM2021NKF-SCM_615; Psoriatic nephropathy has been proposed as a separate entity, with glomerular injury caused chronic T-cell activation and raised levels of immune complexes and cytokines. Similarly, some studies suggest an association between IgA nephropathy and non-Hodgkin lymphoma; postulated to be a paraneoplastic process, with immune complex deposition and complement activation. CONCLUSION This case contributes to the growing literature of IgA nephropathy associated with both psoriasis and non-Hodgkin lymphoma, and highlights the importance of screening for renal dysfunction in both conditions so as to optimize management and prevent significant decline in renal function.
- |||||||||| Leukeran (chlorambucil) / GSK
Journal: Leukostasis in Chronic Lymphocytic Leukemia. (Pubmed Central) - Feb 23, 2021 She required induction chemotherapy with chlorambucil as well as 2 sessions of leukapheresis, to which she responded well...It should be strongly considered in the differential diagnosis of patients with CLL who present with hyperleukocytosis and acute pulmonary symptoms. Clinicians should be aware of this medical emergency, as delayed treatment can increase morbidity and mortality.
- |||||||||| Leukeran (chlorambucil) / GSK
Journal: Promote Dual-Targeting Anticancer Effect by Regulating the Dynamic Intracellular Self-Assembly. (Pubmed Central) - Feb 23, 2021 To prove the concept, fluorescent endoplasmic reticulum (ER)-targeted short peptides were covalently connected to chemotherapy medication Chlorambucil achieving enhanced drug loading efficiency. Via visualized intracellular dynamic enzyme-catalyzed hydrolysis, ER-targeting excipient and nucleus-targeting Chlorambucil are released simultaneously, reaching synergistic anticancer effect and elucidating the influence of intracellular self-assembly transition on enzymatic reactions.
- |||||||||| 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.
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