- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi
Use of De Novo mTOR Inhibitors in Highly Sensitized Kidney Transplant Recipients (Hynes Halls C & D: Board No. D199) - May 20, 2022 - Abstract #ATC2022ATC_2973;
Immunosuppression was based on CNI (tacrolimus), steroids and alternatively mycophenolic acid (MPA; n = 20), or mTORi (either everolimus or sirolimus, n = 96, target trough levels 4-8 ng/mL)... This single-center retrospective cohort one-year analysis suggests that in hypersensitized kidney transplant recipients receiving tacrolimus-based immunosuppressive therapy, similar clinical outcomes may be obtained using mTOR inhibitors compared to mycophenolate.
- |||||||||| everolimus / Generic mfg.
Viral-Specific Cytotoxic T-Cell Responses in Hla-Sensitized Kidney Transplant Patients Maintained on Everolimus and Low Dose Tacrolimus (Hynes Halls C & D: Board No. D185) - May 20, 2022 - Abstract #ATC2022ATC_2961;
*Purpose: Post-transplant immunosuppression with “everolimus + reduced dose tacrolimus” (Ev + Taclow) is reported to reduce the risk of viral infections compared to standard doses of “tacrolimus + mycophenolate mofetil” (Tac + MMF)...* HS kidney transplant patients received desensitization with IVIg + rituximab + PLEX and when transplanted, induction with Campath... CMV-Tc, EBV-Tc, and viremia levels were similar in Ev + Taclow and Tac + MMF patients, suggesting no benefit of Ev + Taclow v. Tac + MMF in enhancing viral-specific Tc effector functions in highly-HLA sensitized kidney transplant patients.
- |||||||||| sirolimus / Generic mfg.
Sirolimus Use Is Associated With An Improved Immune Response To Covid-19 Vaccination In Kidney Transplant Recipients (Hynes Halls C & D: Board No. B316) - May 20, 2022 - Abstract #ATC2022ATC_2770;
KTRs were most commonly receiving the standard-of-care (SOC) triple therapy: tacrolimus, mycophenolate mofetil, prednisolone...In an extended cohort, patients on mTOR inhibitors (mTORi; sirolimus or everolimus) achieved 4-fold higher rates of serological neutralisation than those on SOC therapy (34.6% vs 7.9%)... These data underscore priority vaccination of cohabitants as an effective strategy to protect KTRs, and support a randomised controlled trial of immunosuppression modification with sirolimus as a strategy to directly improve vaccine responses in KTRs.
- |||||||||| Influence of Immunosuppressive Drugs on Nk Cells in Therapeutic Drug Exposured (Hynes Halls C & D: Board No. C021) - May 20, 2022 - Abstract #ATC2022ATC_2753;
Exposure to immunosuppressants impaired the killing ability of NK cells in varying degrees. The inhibition effect of combination therapies is the strongest, followed by steroid, MMF and mTOR inhibitors, and steroid accounts for the main inhibitory component in the combination therapy.
- |||||||||| everolimus / Generic mfg.
Suppressive Effect of De Novo Everolimus on Primary Cytomegalovirus Infection in Kidney Transplant Recipient (Hynes Halls C & D: Board No. C166) - May 20, 2022 - Abstract #ATC2022ATC_2493;
The incidence within 1 year and the time of primary CMV infection, the incidence of CMV disease which required ganciclovir(GCV), and the rate of CMV-antibody acquisition were analyzed retrospectively... EVR as immunosuppressive induction therapy could delay the primary CMV infection after discontinuation of prophylactic VGCV and suppress the development of CMV disease.
- |||||||||| everolimus / Generic mfg.
Comparison of IGG and IGM Type B Cell Receptor-Mediated MTOR Phosphorylation Signal (Hynes Halls C & D: Board No. C006) - May 20, 2022 - Abstract #ATC2022ATC_2193;
Additionally, We compared the effects of everolimus (EVR; 0, 2.5, 5, and 10 ng/mL) on IgM mBC survival, proliferation, and class switching into IgG, and IgG mBC survival, proliferation, and differentiation into plasma cell in vitro... Our findings might indicate IgM mBCs are sensitive to the less mTOR inhibitor administration than to IgG mBCs, and mTOR administration before IgM mBC class-switch into IgG- might prevent IgG PCs development more efficiently and its application will lead to an effective administration method to suppress the development of AMR and improve the prognosis of transplanted grafts after further elucidation of the effects of mTOR inhibitor on regulatory cells.
- |||||||||| Campath (alemtuzumab) / Sanofi
Treatment of BK Virus with Weekly Intravenous Immunoglobulin in Adult Kidney Transplant Recipients (Hynes Halls C & D: Board No. C147) - May 20, 2022 - Abstract #ATC2022ATC_2089;
Treatment of BKV with IVIG 0.1 g/kg weekly for 10 weeks without additional alternative therapies provided a significant reduction in BK viral log10 at 3 and 6 months post IVIG in KTR with persistent BKV despite reduction in IS. Further comparative studies are needed however this review highlights the potential efficacy of weekly IVIG in KTR not on additional anti-virals.
- |||||||||| everolimus / Generic mfg.
Phase I/ii Car-Treg Cell Therapy Clinical Trial To Induce Long-term Tolerance In Liver Transplant Patients (Hynes Room 313) - May 20, 2022 - Abstract #ATC2022ATC_1296;
Baseline IS includes low-dose Tacrolimus and Everolimus and part 2 participants will receive a conditioning regimen. This trial, which is currently recruiting, will provide first evidence in humans whether CAR-Tregs are a safe and/or effective therapeutic approach to induce tolerance in LT patients with broad implications for other transplant and non-transplant indication areas.
- |||||||||| imlunestrant (LY3484356) / Eli Lilly
Trial completion date, Combination therapy, Monotherapy, Metastases: EMBER: A Study of LY3484356 in Participants With Advanced or Metastatic Breast Cancer or Endometrial Cancer (clinicaltrials.gov) - May 20, 2022
P1a/1b, N=500, Recruiting,
This trial, which is currently recruiting, will provide first evidence in humans whether CAR-Tregs are a safe and/or effective therapeutic approach to induce tolerance in LT patients with broad implications for other transplant and non-transplant indication areas. Trial completion date: Apr 2023 --> Dec 2023
- |||||||||| Clinical, Review, Journal: Clinical Review on the Management of Hormone Receptor-Positive Metastatic Breast Cancer. (Pubmed Central) - May 19, 2022
In the past decade, the introduction of molecularly targeted agents against intracellular targets such as mammalian target of rapamycin (everolimus), cyclin-dependent kinases 4 and 6 (palbociclib, ribociclib, and abemaciclib), and phosphatidylinositol 3-kinase (alpelisib) has offered patients effective nonchemotherapy-based options, which are improving outcomes...Still, formatting a plan for these patients includes taking into account traditional prognostic factors such as menopausal status, previous treatments, disease-free interval for those patients with early breast cancer that has recurred, and tumor burden. To assist in developing this treatment plan, we will review the current data with systemic agents in the management of these patients.
- |||||||||| everolimus / Generic mfg.
Enrollment change, Trial termination: Everolimus Modulation of Anti-tumor T CD4 Immune Responses (clinicaltrials.gov) - May 16, 2022
P=N/A, N=14, Terminated,
Trial completion date: Jun 2022 --> Dec 2024 | Trial primary completion date: Jun 2022 --> Dec 2024 N=60 --> 14 | Recruiting --> Terminated; difficulty of patient recruitment
- |||||||||| everolimus / Generic mfg.
Journal: Vitamin D Reverts the Exosome-Mediated Transfer of Cancer Resistance to the mTOR Inhibitor Everolimus in Hepatocellular Carcinoma. (Pubmed Central) - May 14, 2022
Interestingly, the treatment with VitD prevented exosome-induced EVE resistance in HCC cells, significantly inhibiting cell proliferation but also partially reducing colony and size number when combined with EVE compared with control. In conclusion, the results of the current study demonstrated that exosomes derived from EveR cells could induce EVE resistance in EVE-sensitive HCC cells and that VitD can revert the exosome-induced EVE resistance by resensitizing to EVE treatment.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie
CHARACTERIZATION OF VENETOCLAX RESISTANCE IN CELL MODELS OF MANTLE CELL LYMPHOMA () - May 13, 2022 - Abstract #EHA2022EHA_1696;
However, 2-day pre-treatment with epigenetic drugs (Vorinostat, Tazemetostat, Valemostat and Azacytidine) and 7-day pre-treatment with Tazemetostat + Azacytidine had no effect on Ven sensitivity...Inhibition of mTORC1 with Everolimus abrogated the toxic effect of Ven in the maternal cell lines (figure 1E), whereas TIC-10, an AKT/MEK inhibitor, partially restored Ven sensitivity in MAVER1-VR and MINO-VR cell lines (figure 1D)...The PI3K-AKT-mTOR pathway appears to be involved in Ven resistance development, since interestingly, mTOR inhibition leads to a decreased response to Ven treatment in maternal cell lines but AKT inhibition leads to an increased response in -VR cell lines. Ven resistance in MINO-VR appears to be driven primarily by decreased mitochondrial priming, whereas MAVER-VR appears to be driven by decreased mitochondrial priming combined with a switch from BCL2 to MCL1 dependence.
- |||||||||| Journal, PARP Biomarker: Personalized drug testing in human pheochromocytoma/paraganglioma primary cultures. (Pubmed Central) - May 12, 2022
Single anti-cancer drugs were either more effective in cluster 1 (cabozantinib, selpercatinib, and 5-FU) or similarly effective in both clusters (everolimus, sunitinib, alpelisib, trametinib, niraparib, entinostat, gemcitabine, AR-A014418, and high-dose zoledronic acid)...Neither cluster 1- nor cluster 2-related patient primary cultures responded to HIF-2a inhibitors, temozolomide, dabrafenib, or octreotide...Cabozantinib/everolimus combination therapy, gemcitabine, and high-dose zoledronic acid appear to be promising treatment options with particularly high efficacy in SDHB-mutant and metastatic tumors. In conclusion, only minor differences regarding drug responsivity were found between cluster 1 and cluster 2: some single anti-cancer drugs were more effective in cluster 1 and some targeted combination treatments were more effective in cluster 2.
- |||||||||| Avastin (bevacizumab) / Roche
Journal: Everolimus with or without bevacizumab in advanced pNET: CALGB 80701 (Alliance). (Pubmed Central) - May 12, 2022
In summary, treatment with everolimus and bevacizumab led to superior progression-free survival and higher response rates compared to everolimus in patients with advanced pancreatic neuroendocrine tumors. Although the higher rate of treatment related adverse events may limit the use of this combination, our results support the continued evaluation of VEGF pathway inhibitors in pancreatic neuroendocrine tumors.
- |||||||||| xentuzumab (BI-836845) / Boehringer Ingelheim
Trial completion, Combination therapy, Metastases: The XENERA (clinicaltrials.gov) - May 12, 2022
P2, N=103, Completed,
There were no serious complications. Active, not recruiting --> Completed
- |||||||||| Paxlovid (nirmatrelvir and ritonavir) / Pfizer
Journal: Using nirmatrelvir/ritonavir in patients with epilepsy: an update from the Israeli ILAE Chapter. (Pubmed Central) - May 10, 2022
Presented herein are recommendations for use of nirmatrelvir/ritonavir in patients with epilepsy, as issued by the Steering Committee of the Israeli Chapter of the International League Against Epilepsy. The recommendations suggest that patients on moderate-to-strong enzyme-inducing antiseizure medications (ASMs) and everolimus should not be treated with nirmatrelvir/ritonavir; rectal diazepam may be used as an alternative to buccal midazolam; doses of ASMs that are CYP3A4 substrates might be adjusted; patients treated with combinations of nirmatrelvir/ritonavir and ASMs that are CYP3A4 substrates or lamotrigine should be monitored for drug efficacy and adverse reactions.
- |||||||||| Retrospective data, Review, Journal: Aftercare and adjuvant therapy for advanced renal cell carcinoma (Pubmed Central) - May 10, 2022
However, overall survival results are pending. Other potentially effective adjuvant concepts including atezolizumab, nivolumab/ipilimumab, everolimus or pembrolizumab/belzutifan are currently being investigated in clinical trials.
- |||||||||| veliparib (ABT-888) / AbbVie, Mekinist (trametinib) / Novartis, BeiGene, adavosertib (AZD1775) / AstraZeneca
Trial completion, Enrollment change, Trial primary completion date, Metastases: MPACT Study to Compare Effects of Targeted Drugs on Tumor Gene Variations (clinicaltrials.gov) - May 10, 2022
P2, N=208, Completed,
In conclusion, 5-aza-dC combined with RAD001 effectively controlled OCCC and OCCCSC growth by inhibiting the COL6A3-AKT-mTOR pathway. Active, not recruiting --> Completed | N=700 --> 208 | Trial primary completion date: May 2022 --> Jun 2021
- |||||||||| Farydak (panobinostat) / Secura Bio, Torisel (temsirolimus) / Pfizer
Biomarker, Clinical data, Journal, Tumor Mutational Burden, Tumor microenvironment, IO biomarker, Epigenetic controller: Identification of Tumor Microenvironment and DNA Methylation-Related Prognostic Signature for Predicting Clinical Outcomes and Therapeutic Responses in Cervical Cancer. (Pubmed Central) - May 7, 2022
Finally, four drugs (panobinostat, lenvatinib, everolimus, and temsirolimus) were found to have potential therapeutic implications for patients with a high-risk score. Our findings highlight that the TME and DNA methylation-related prognostic signature can accurately predict the prognosis of CC and may be important for stratified management of patients and precision targeted therapy.
- |||||||||| Lenvima (lenvatinib) / Eisai, Merck (MSD)
Trial completion date, Trial primary completion date, Metastases: Lenvatinib and Everolimus in Renal Cell Carcinoma (RCC) (clinicaltrials.gov) - May 6, 2022
P1, N=15, Recruiting,
Briefly, RAD001 combined with PD-1 blockade increases radiosensitivity of CC by impeding the PI3K/AKT/mTOR pathway and potentiating cell autophagy. Trial completion date: Apr 2022 --> Apr 2024 | Trial primary completion date: Apr 2022 --> Apr 2023
- |||||||||| everolimus / Generic mfg.
Clinical, Journal: STAT3 polymorphism associates with mTOR inhibitor-induced interstitial lung disease in patients with renal cell carcinoma. (Pubmed Central) - May 6, 2022
An in vitro study demonstrated that some lung-derived cell lines carrying the CC genotype exhibited an increase in the expression of mesenchymal markers, such as fibronectin, N-cadherin, and vimentin and decreases in E-cadherin, which is an epithelial marker associated with exposure to everolimus, although STAT3 expression and activity were not related to the genotype. In conclusion, the CCgenotype of the STAT3 rs4796793 polymorphism increases the risk of mTOR inhibitorinduced ILD, supporting its use as a predictive marker for RCC.
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