Integrated Safety Profile of Selinexor in Multiple Myeloma
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Bulletin L'académie Nationale De Médecine
Tome 202 — Mai et Juin — N os 5-6 2018 BULLETIN DE L’ACADÉMIE NATIONALE DE MÉDECINE publié par MM. Daniel C, Secrétaire perpétuel et Jean François A , Secrétaire adjoint Rédacteur en chef : Professeur Jean-Noël F Adjointe à la Rédaction : Sibylle du C ACADÉMIE NATIONALE DE MÉDECINE 16, RUE BONAPARTE — 75272 PARIS CEDEX 06 http://www.academie-medecine.fr 2018 — Tome 202 — Mai-Juin — N os 5-6 Sommaire BULLETIN DE L’ACADÉMIE NATIONALE DE MÉDECINE publié par MM. Daniel C, Secrétaire perpétuel et Jean François A , Secrétaire adjoint Rédacteur en chef : Professeur Jean-Noël F Adjointe à la Rédaction : Sibylle du C sommaire Rapports 817 Rapport 18-03. Efficacité et effets indésirables des statines : évidences et polémiques Efficacy and side effects of statin therapy: a reappraisal Michel Komajda, au nom de la Commission IV (Maladies cardiovasculaires) 837 Rapport 18-04. La place de la France dans les essais cliniques à promotion industrielle Yvon Lebranchu (Rapporteur), Au nom d’un groupe de travail rattaché à la Commission II (Thérapeutique-Pharmacologie-Toxicologie-Médicaments et autres produits de santé) 859 Rapport 18-05. La biologie médicale face aux défis de l’évolution des besoins de santé Medical biology in the face of the evolution of health care needs Claude Dreux, François-Xavier Maquart (rapporteurs), au nom du groupe de travail inter-académique de l’Académie nationale de médecine et de l’Aca- démie nationale de Pharmacie. 873 Rapport 18-06. La demande d’une nouvelle orientation (rhumatologie) par l’établissement thermal de Vals-les-Bains Daniel Bontoux et Christian Roques 811 Académie nationale de Médecine Communiqué 883 À propos de la dépénalisation de la consommation de cannabis Jean-Pierre. -
Therapeutic Class Overview Colony Stimulating Factors
Therapeutic Class Overview Colony Stimulating Factors Therapeutic Class Overview/Summary: This review will focus on the granulocyte colony stimulating factors (G-CSFs) and granulocyte- macrophage colony stimulating factors (GM-CSFs).1-5 Colony-stimulating factors (CSFs) fall under the naturally occurring glycoprotein cytokines, one of the main groups of immunomodulators.6 In general, these proteins are vital to the proliferation and differentiation of hematopoietic progenitor cells.6-8 The G- CSFs commercially available in the United States include pegfilgrastim (Neulasta®), filgrastim (Neupogen®), filgrastim-sndz (Zarxio®), and tbo-filgrastim (Granix®). While filgrastim-sndz and tbo- filgrastim are the same recombinant human G-CSF as filgrastim, only filgrastim-sndz is considered a biosimilar drug as it was approved through the biosimilar pathway. At the time tbo-filgrastim was approved, a regulatory pathway for biosimilar drugs had not yet been established in the United States and tbo-filgrastim was filed under its own Biologic License Application.9 Only one GM-CSF is currently available, sargramostim (Leukine). These agents are Food and Drug Administration (FDA)-approved for a variety of conditions relating to neutropenia or for the collection of hematopoietic progenitor cells for collection by leukapheresis.1-5 Due to the pathway taken, tbo-filgrastim does not share all of the same indications as filgrastim and these two products are not interchangeable. It is important to note that although filgrastim-sndz is a biosimilar product, and it was approved with all the same indications as filgrastim at the time, filgrastim has since received FDA-approval for an additional indication that filgrastim-sndz does not have, to increase survival in patients with acute exposure to myelosuppressive doses of radiation.1-3A complete list of indications for each agent can be found in Table 1. -
FULPHILA Safely and Effectively
HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use FULPHILA safely and effectively. See full prescribing information for -----------------------WARNINGS AND PRECAUTIONS---------------------- FULPHILA. • Fatal splenic rupture: Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture. (5.1) ™ FULPHILA (pegfilgrastim-jmdb) injection, for subcutaneous use • Acute respiratory distress syndrome (ARDS): Evaluate patients who Initial U.S. Approval: 2018 develop fever, lung infiltrates, or respiratory distress. Discontinue ™ ® Fulphila in patients with ARDS. (5.2) FULPHILA (pegfilgrastim-jmdb) is biosimilar* to NEULASTA • Serious allergic reactions, including anaphylaxis: Permanently (pegfilgrastim). (1) discontinue Fulphila in patients with serious allergic reactions. (5.3) • Fatal sickle cell crises: Have occurred. (5.4) ----------------------------INDICATIONS AND USAGE--------------------------- • Glomerulonephritis: Evaluate and consider dose-reduction or Fulphila is a leukocyte growth factor indicated to interruption of Fulphila if causality is likely. (5.5) • Decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving ------------------------------ADVERSE REACTIONS------------------------------ myelosuppressive anti-cancer drugs associated with a clinically Most common adverse reactions (≥ 5% difference in incidence compared to significant incidence of febrile neutropenia. -
Phase I Study of Selinexor in Combination With
Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma by Tiffany Tang, Peter Martin, Nagavalli Somasundaram, Cindy Lim, Miriam Tao, Eileen Poon, Maica J.D. Yunon, Shu Q. Toh, Sean X. Yan, Mohamad Farid, Jason Y. Chan, and Soon T. Lim Haematologica 2020 [Epub ahead of print] Citation: Tiffany Tang, Peter Martin, Nagavalli Somasundaram, Cindy Lim, Miriam Tao, Eileen Poon, Maica J.D. Yunon, Shu Q. Toh, Sean X. Yan, Mohamad Farid, Jason Y. Chan, and Soon T. Lim. Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma. Haematologica. 2020; 105:xxx doi:10.3324/haematol.2020.251454 Publisher's Disclaimer. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have completed a regular peer review and have been accepted for publication. E-publishing of this PDF file has been approved by the authors. After having E-published Ahead of Print, manuscripts will then undergo technical and English editing, typesetting, proof correction and be presented for the authors' final approval; the final version of the manuscript will then appear in print on a regular issue of the journal. All legal disclaimers that apply to the journal also pertain to this production process. Article type: Original Article Title: Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural- killer/T-cell lymphoma. -
Selinexor (Xpovio™) (Updated November 2019)
selinexor (Xpovio™) EOCCO POLICY Policy Type: PA/SP Pharmacy Coverage Policy: EOCCO086 Description Selinexor (Xpovio) is an oral nuclear export inhibitor. Length of Authorization Initial: Six months Renewal: 12 months Quantity Limits Product Name Dosage Form Indication Quantity Limit 80 mg tablet twice weekly carton 1 carton (32 tablets)/28 days 100 mg tablet once weekly carton 1 carton Relapsed or (20 tablets)/28 days 80 mg tablet once weekly carton refractory multiple 1 carton myeloma (MM) (16 tablets)/28 days selinexor 60 mg tablet once weekly carton 1 carton (Xpovio) (12 tablets)/28 days 40 mg tablet once weekly carton 1 carton (8 tablets)/28 days 60 mg tablet twice weekly carton Relapsed or 1 carton refractory diffuse (24 tablets)/28 days 40 mg tablet twice weekly carton large B-cell 1 carton lymphoma (DLBCL) (16 tablets)/28 days Initial Evaluation I. Selinexor (Xpovio) may be considered medically necessary when the following criteria are met: A. Member is 18 years of age or older; AND B. Medication is prescribed by, or in consultation with, a hematologist or oncologist; AND C. Not used in combination with any other oncology therapy unless outlined below; AND D. A diagnosis of multiple myeloma when ONE of the following are met: 1. The provider attests to the following: i. The member has received ONE, but no more than THREE previous therapies; AND 1 selinexor (Xpovio™) EOCCO POLICY a. Previous treatments included at least one of the following medications: i. Bortezomib (Velcade) ii. Carfilzomib (Kyprolis) iii. Ixazomib (Ninlaro) iv. Daratumumab (Darzalex) v. Immunomodulatory agent (e.g., lenalidomide, pomalidomide); AND b. -
Comparison Between Filgrastim and Lenograstim Plus Chemotherapy For
Bone Marrow Transplantation (2010) 45, 277–281 & 2010 Macmillan Publishers Limited All rights reserved 0268-3369/10 $32.00 www.nature.com/bmt ORIGINAL ARTICLE Comparison between filgrastim and lenograstim plus chemotherapy for mobilization of PBPCs R Ria, T Gasparre, G Mangialardi, A Bruno, G Iodice, A Vacca and F Dammacco Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy Recombinant human (rHu) G-CSF has been widely used during transplantation.4 However, the use of G-CSF after to treat neutropenia and mobilize PBPCs for their autologous PBPC transplantation has been queried, as its autologous and allogeneic transplantation. It shortens further reduction in time to a safe neutrophil count5,6 does neutropenia and thus reduces the frequency of neutropenic not always imply fewer significant clinical events, such as fever. We compared the efficiency of glycosylated rHu infections, length of hospitalization, extrahematological and non-glycosylated Hu G-CSF in mobilizing hemato- toxicities or mortality.7,8 Even so, the ASCO guidelines still poietic progenitor cells (HPCs). In total, 86 patients were recommend the use of growth factors after autologous consecutively enrolled for mobilization with CY plus either PBPC transplantation.9 glycosylated or non-glycosylated G-CSF, and under- G-CSF induces the proliferation and differentiation of went leukapheresis. The HPC content of each collection, myeloid precursor cells, and also provides a functional toxicity, days of leukapheresis needed to reach the activity that influences chemotaxis, respiratory burst and minimum HPC target and days to recover WBC (X500 Ag expression of neutrophils. -
Targeting CRM1 in AML (Presented at ESH – Budapest)
Targeting CRM1 in AML Gert Ossenkoppele & colleagues VU University Medical Center Amsterdam Approved Treatment Options for AML Compared to Other Hematologic Malignancies US approvals EU approvals Subsequently withdrawn Non-Hodgkin Lymphoma Acute Lymphoblastic Leukemia Multiple Myeloma Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Acute Myeloid Leukemia 1995 2000 2005 2010 2015 1. NCI Drug Info. http://www.cancer.gov/cancertopics/druginfo. 2. EMA Drug Approvals. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landing_page.jsp&mid=. 3. FDA Drug Approvals. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm.. 3. NCCN clinical practice guidelines in oncology: acute myeloid leukemia. National Comprehensive Cancer Network website. V.2.2014. http://www.nccn.org/professionals/physician_gls/PDF/aml.pdf Selective Inhibitors of Nuclear Export(SINE) (SINE) • Cancer cells can inactivate their Tumor Suppressor Proteins (TSPs) via nuclear export • Exportin 1 (XPO1, CRM1) is the exclusive nuclear exporter of most TSPs • XPO1 is elevated in Acute Myeloid Leukemia (AML), Chronic Lymphocytic Leukemia (CLL), NHL and other malignancies • Selinexor (KPT-330) is a covalent, oral Selective Inhibitor of Nuclear Export (SINE) that blocks XPO1 Selinexor: Novel Anti-Cancer Agent: Restores Tumor Suppressors & Reduces Oncoproteins Cell Membrane CYTOPLASM Tumor Suppressors XPO-1 Tumor Suppressors p53 Par-4 PP2A pRB Nuclear Pore Complex p21 SINE IkB Nuclear Envelope BRCA1 p27 Tumor Suppressors elF4E (myc,bcl2) Selinexor: -
Parkinson's Disease Fact Sheet
Parkinson’s Disease Fact Sheet About Parkinson’s Disease Parkinson’s disease is a progressive, incurable neurological disorder associated with a loss of dopamine-generating cells in the brain. It is primarily associated with progressive loss of motor control, but it results in a complex array of symptoms, including many non-motor symptoms. Parkinson’s impacts an estimated one million people in the United States. Critical Clinical Care Considerations • To avoid serious side effects, Parkinson’s patients need their medications on time, every time — do not skip or postpone doses. • Write down the exact times of day medications are to be administered so that doses are given on the same schedule the patient follows at home. • Do not substitute Parkinson’s medications or stop levodopa therapy abruptly. • Resume medications immediately following procedures, unless vomiting or severely incapacitated. • If an antipsychotic is necessary, use pimavanserin (Nuplazid), quetiapine (Seroquel) or clozapine (Clozaril). • Be alert for symptoms of dysphagia (trouble swallowing) and risk of pneumonia. • Ambulate as soon as medically safe. Patients may require assistance. Common Symptoms of Parkinson’s Disease Motor Non-Motor • Shaking or tremor at rest • Depression • Bradykinesia or freezing (being stuck • Anxiety in place when attempting to walk) • Constipation • Low voice volume or muffled speech • Cognitive decline and dementia • Lack of facial expression • Impulse control disorders • Stiffness or rigidity of the arms, legs • Orthostatic hypotension or -
Filgrastim Vs Pegfilgrastim: a Quality of Life Issue for Children
FEATURE | Filgrastim vs pegfilgrastim Filgrastim vs pegfilgrastim: A quality of life issue for children Administration, safety, and efficacy are similar in both agents.H owever, the frequency of administration makes a significant difference for patients. KAREN E. MACDonaLD, BSN, RN, CPON; HAYLEY BEE, BSN, RN, CPN, CCRN; DARBY TOZER, BSN, RN; JEnnIFER E. TRAIN, BSN, RN ancer is diagnosed in 1.5 million people in the United States each year, and more than 12,000 cancer patients are younger C 1 than 21 years. Parents sit across the table from the medical team and learn about the side effects of treatment that their child may experience. The child will lose his or her hair, miss school, experience nausea and vomiting, and endure multiple laboratory and diagnostic tests. Families learn that their day-to-day life, once filled with school, work, soccer games, and other family- centered activities, will now consist of hospital admissions, doctor visits, and isolation to abate the possible side effects of treatment. In addition, parents will need to learn how to administer clinical care, such as subcutaneous injections of medications to improve the child’s immune system, at home. Neutrophils are a critical member of the phago- cytic system and provide a first-line defense against bacterial organisms.2 Neutropenia is defined as a reduction in circulating neutrophils to less than 1,500/µL.1 Chemotherapy-induced neutropenia is the primary treatment-related dose-limiting toxicity in children with can- cer. Severe neutropenia (neutrophils less than 500/µL) can occur as a result of chemotherapy treatment. Children who receive intensive che- motherapy have a 40% chance of developing 3 © THINKSTOCK © febrile neutropenia. -
G-CSF Protects Motoneurons Against Axotomy-Induced Apoptotic Death In
Henriques et al. BMC Neuroscience 2010, 11:25 http://www.biomedcentral.com/1471-2202/11/25 RESEARCH ARTICLE Open Access G-CSF protects motoneurons against axotomy- induced apoptotic death in neonatal mice Alexandre Henriques1,2,3, Claudia Pitzer1*, Luc Dupuis2,3, Armin Schneider1* Abstract Background: Granulocyte colony stimulating factor (G-CSF) is a growth factor essential for generation of neutrophilic granulocytes. Apart from this hematopoietic function, we have recently uncovered potent neuroprotective and regenerative properties of G-CSF in the central nervous system (CNS). The G-CSF receptor and G-CSF itself are expressed in a motoneurons, G-CSF protects motoneurons, and improves outcome in the SOD1(G93A) transgenic mouse model for amyotrophic lateral sclerosis (ALS). In vitro, G-CSF acts anti- apoptotically on motoneuronal cells. Due to the pleiotrophic effects of G-CSF and the complexity of the SOD1 transgenic ALS models it was however not possible to clearly distinguish between directly mediated anti- apoptotic and indirectly protective effects on motoneurons. Here we studied whether G-CSF is able to protect motoneurons from purely apoptotic cell death induced by a monocausal paradigm, neonatal sciatic nerve axotomy. Results: We performed sciatic nerve axotomy in neonatal mice overexpressing G-CSF in the CNS and found that G-CSF transgenic mice displayed significantly higher numbers of surviving lumbar motoneurons 4 days following axotomy than their littermate controls. Also, surviving motoneurons in G-CSF overexpressing animals were larger, suggesting additional trophic effects of this growth factor. Conclusions: In this model of pure apoptotic cell death the protective effects of G-CSF indicate direct actions of G-CSF on motoneurons in vivo. -
Together with CCHP's Medication List Prior Authorization Is Required If Indicated by X(PA)
Together with CCHP's Medication List Prior authorization is required if indicated by X(PA). Pharmacy Benefit: Submit authorizations through Together with CCHP's Pharmacy Services. Medical Benefit: Submit authorizations through CareWeb Qi Authorization tool. Jcode Brand Name Description Pharmacy Medical Notes J3365 Abbokinase INJECTION, UROKINASE, 250,000 IU X J0287 Abelcet INJECTION, AMPHOTERICIN B LIPID X COMPLEX, 10 MG J0401 Abilify Maintena INJECTION, ARIPIPRAZOLE, EXTENDED X X May bIll eIther RELEASE, 1 MG (PA < 12 YEARS OF benefIt, PA AGE) reQuIred when bIllIng through pharmacy INJECTION, PACLITAXEL PROTEIN- J9264 Abraxane BOUND PARTICLES, 1 MG X J7613 Accuneb ALBUTEROL, INHALATION SOLUTION, X FDA- APPROVED FINAL PRODUCT, NONCOMPOUNDED, ADMINISTERED THROUGH DME, UNIT DOSE, 1 MG J0132 Acetadote INJECTION, ACETYLCYSTEINE, 100 MG X J7608 Acetylcysteine ACETYLCYSTEINE, INHALATION X SOLUTION, FDA- APPROVED FINAL PRODUCT, NONCOMPOUNDED, ADMINISTERED THROUGH DME, UNIT DOSE FORM, PER G J3262 Actemra INJECTION, TOCILIZUMAB, 1 MG X (PA) J0800 Acthar Gel INJECTION, CORTICOTROPIN, UP TO 40 X (PA) UNITS J0795 Acthrel INJECTION, CORTICORELIN OVINE X TRIFLUTATE, 1 MCG J9216 Actimmune INTERFERON GAMMAM 1-B X (PA) J2997 Activase INJECTION, ALTEPLASE RECOMBINANT, X 1 MG J2504 Adagen PEGADEMASE BOVINE 25 IU X (PA) J2062 Adasuve LoxapIne, InhalatIon powder, 10 mg X INJECTION, BRENTUXIMAB VEDOTIN, 1 J9042 Adcetris X MG 1 Together with CCHP's Medication List Prior authorization is required if indicated by X(PA). Pharmacy Benefit: Submit authorizations -
©Ferrata Storti Foundation
Stem Cell Transplantation • Research Paper Single-dose pegfilgrastim for the mobilization of allogeneic CD34+ peripheral blood progenitor cells in healthy family and unrelated donors Frank Kroschinsky Background and Objectives. Short-term treatment with granulocyte colony-stimulating Kristina Hölig factor (G-CSF) has been established as the standard regimen for mobilizing allogeneic Kirsten Poppe-Thiede peripheral blood progenitor cells (PBPC) from healthy donors. The pegylated form of fil- Kristin Zimmer grastim (pegfilgrastim) has a longer elimination half-life because of decreased serum Rainer Ordemann clearance and might be a convenient alternative for stem cell mobilization. Matthias Blechschmidt Uta Oelschlaegel Design and Methods. Twenty-five family (n=15) or unrelated (n=10) healthy donors received a single-dose of 12 mg pegfilgrastim for mobilization of allogeneic PBPC. Martin Bornhauser + Gabi Rall Donors with inadequate mobilization (blood CD34 cells ≤5/µL on day 3 or ≤20/µL on Claudia Rutt day 4) were given additional daily doses of 10 µg/kg conventional filgrastim. Gerhard Ehninger Leukapheresis was planned to start on day 5. Results. All harvests were completed successfully. In 20 out of 25 donors (80 %) only a single apheresis was necessary. Additional non-pegylated filgrastim had to be given to only one 74-year old family donor. The maximum concentration of circulating CD34+ + cells occurred on day 5 (median 67/µL, range 10-385/µL). The median yield of CD34 cells was 9.3 (range 3.2-39.1) 106/kg of the recipient´s body weight. The median × 8 number of T cells in the apheresis products was 3.9 (range 2.7-10.8)×10 /kg.