This phase II trial tested a WT1 peptide vaccine (galinpepimut-S) in 22 adults with acute myeloid leukemia in first complete remission. The vaccine contained four WT1 peptides that induced CD4+ and CD8+ immune responses in 64% and 86% of patients respectively. Median overall survival was 62.5 months and immune responders showed a trend towards improved clinical outcomes. The vaccine was well-tolerated with common adverse events including injection site reactions and transient cytopenias. Upcoming randomized trials will evaluate clinical efficacy.
T cells genetically engineered to express chimeric antigen receptors (CAR) have proven an impressive therapeutic activity in patients with certain subtypes of B cell leukaemia or lymphoma, with promising efficacy also demonstrated in patients with multiple myeloma. However, in patients with solid tumors, objective responses to CAR-T cell therapy remain sporadic and transient. Key challenges relating to CAR T cells include the lack of tumor exclusive target, restricted CAR-T cell trafficking to tumor sites, antigen escape and heterogeneity as well as a highly immunosuppressive microenvironment. In this report, we review the current state of the CAR-T technologies as a clinical treatment in solid tumor and we highlight the preclinical innovative designs of novel CAR T cell products that are being developed to increase and expand the clinical benefits of these treatments in patients with solid malignancies.
Ebmt 2018 gps in mm koehne et al_with suppl slides_final_final_1.1.12_mar2018...Nicholas Sarlis
Galinpepimut-S (WT1-targeting peptide vaccine) in high-risk multiple myeloma. Final results from a Phase 2 clinical study. Koehne G, et al. EBMT 2018 slide presentation.
Presentation focusing on what is cancer immunotherapy is, what are the potential challenges in the safety assessment of antibodies targeting immune system checkpoints, things to consider when designing and running your nonclinical safety programmes for immune checkpoint targets and measuring immunotoxicity / immunopharmacology. It also looks at what if your chosen therapeutic has no pharmacologically relevant non-clinical safety species.
Justin F. Gainor, MD; Kurt Schalper, MD, PhD; and Edward B. Garon, MD, MS prepared useful Practice Aids pertaining to immunotherapy for this CME/MOC/CC/CNE activity titled, "New Frontiers in Precision Immuno-Oncology: Leveraging Biomarkers to Refine and Expand the Use of Cancer Immunotherapies and Combinations." For the full presentation, monograph, complete CME/MOC/CC/CNE information, and to apply for credit, please visit us at http://bit.ly/2UJuQBq. CME/MOC/CC/CNE credit will be available until April 25, 2020.
T cells genetically engineered to express chimeric antigen receptors (CAR) have proven an impressive therapeutic activity in patients with certain subtypes of B cell leukaemia or lymphoma, with promising efficacy also demonstrated in patients with multiple myeloma. However, in patients with solid tumors, objective responses to CAR-T cell therapy remain sporadic and transient. Key challenges relating to CAR T cells include the lack of tumor exclusive target, restricted CAR-T cell trafficking to tumor sites, antigen escape and heterogeneity as well as a highly immunosuppressive microenvironment. In this report, we review the current state of the CAR-T technologies as a clinical treatment in solid tumor and we highlight the preclinical innovative designs of novel CAR T cell products that are being developed to increase and expand the clinical benefits of these treatments in patients with solid malignancies.
Ebmt 2018 gps in mm koehne et al_with suppl slides_final_final_1.1.12_mar2018...Nicholas Sarlis
Galinpepimut-S (WT1-targeting peptide vaccine) in high-risk multiple myeloma. Final results from a Phase 2 clinical study. Koehne G, et al. EBMT 2018 slide presentation.
Presentation focusing on what is cancer immunotherapy is, what are the potential challenges in the safety assessment of antibodies targeting immune system checkpoints, things to consider when designing and running your nonclinical safety programmes for immune checkpoint targets and measuring immunotoxicity / immunopharmacology. It also looks at what if your chosen therapeutic has no pharmacologically relevant non-clinical safety species.
Justin F. Gainor, MD; Kurt Schalper, MD, PhD; and Edward B. Garon, MD, MS prepared useful Practice Aids pertaining to immunotherapy for this CME/MOC/CC/CNE activity titled, "New Frontiers in Precision Immuno-Oncology: Leveraging Biomarkers to Refine and Expand the Use of Cancer Immunotherapies and Combinations." For the full presentation, monograph, complete CME/MOC/CC/CNE information, and to apply for credit, please visit us at http://bit.ly/2UJuQBq. CME/MOC/CC/CNE credit will be available until April 25, 2020.
Immunotherapy for Metastatic Triple Negative Breast Cancerbkling
Sylvia Adams, MD, medical oncologist, and associate professor at the NYU School of Medicine, discusses the latest research including the role of immunology in the treatment of triple negative metastatic breast cancer. This webinar was hosted on October 19, 2016.
Dr. Patrick Hwu presents the latest information on immunotherapies for melanoma at the MRF's Patient Symposium at MD Anderson Cancer Center on January 31, 2015.
ProImmune Antigen Characterization Summit Paul Mossamandacturner
Paul Moss, School of Cancer Sciences, Birmingham UK, presents at the ProImmune Antigen Characterization and Biomarker Discovery Summit, January 2011.
Cytomegalovirus and Cancer-specific Immunity
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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1. Phase II trial of WT1 Analog PeptideVaccine in
adults with Acute Myeloid Leukemia (AML) in
First Complete Remission (CR)
Maslak P, Dao T, Bernal Y, Chanel S, Zhang R, Frattini M, RosenblatT,JurcicJ,
Brentjens R, Rampal R, ParkJ, Douer D, Katz L*, Gutierrez A*,Tallman M, Scheinberg
DA. *Sellas Life ScienceGroup & Memorial Sloan Kettering CancerCenter , NY NY,
10065
2. Background-WT1 as a ImmunologicTarget
• Wilms’ tumor 1 (WT1) gene is a transcription factor with limited expression in normal
tissues.
• WT1 is over-expressed in AML,CML, ALL and several solid tumors including mesothelioma,
lung, breast, prostate and ovarian cancers.
• WT1 is found in early leukemia progenitors (CD34+) and possibly LSC’s.
• Expression of WT1 has been reported to be a prognostic marker as well as an indicator of
minimal residual disease in AML and MDS.
• WT1 is processed and presented to the immune system.
• “Heteroclitic” analog WT1 peptides can induce a reactiveT cell response to native peptides.
• Peptide vaccines derived from WT1 protein can induce CTL recognition and killing of WT1
expressing leukemia cell lines
4. Phase II galinpepimut-S (GPS)Trial Design
• Eligibility:
– Age > 18 yrs
– Completed all planned chemotherapy
– WT1 + pcr
– CR1- documentation of prior AML
diagnosis
• Treatment :
‒ Four WT1 peptides
(331,427,122A1,WT1-A1) 200 mcg each
‒ Montanide (1:1 volume) adjuvant
‒ GM-CSF 70 mcg- Days -2 and 0
‒ 6 vaccines weeks 0,2,4,6,8,10
‒ If no POD 6 additional vaccines Q
month
• Monitoring
– Immune response (after 6 /12 vaccines)
• HLA-A02: CD8+ response
– IFN-γ ELISPOT
– WT1-A / Ao2o1 tetramer
• CD4+ response :T cell proliferation
– WT1 levels in BM (after 6 /12 vaccines or
end of study)
– Bone marrow evaluation at 12 / 40 weeks
or end of study
5. Study Patient Characteristics
(N=22)
MedianAge, y (range) 63 (23-75)
Male (%) 32
Median KPS 90 (80-100)
HLA-A0201 9
Risk Status (LeukemiaNet), n (%)
Favorable 8 (36.4)
Intermediate 1 7 (31.8)
Intermediate 2 3 (13.6)
Adverse 3 (13.6)
Undetermined 1 (4.5)
PriorTherapies Ara-C +Anthracycline : 95%
Post-remission 1-2x : 36%
Post-remission 3-4x : 59%
Median time to vaccine, m (range) 8 (3-22)
6. Clinical outcomes
• Completed vaccinations
– 64% : 6
– 45% : 12
• 15 patients relapsed
– 10 while receiving GPS
• 4 after 1 vaccine
• 5 received salvage HSCT
• Median DFS: 23.75 mos
• 12 Alive
– 9 in 1st CR
– 3 post- HSCT (11,19 &31 mos)
• 10 Dead
– 9 relapsed disease
– 1 infection post-HSCT
• Median OS: 62.5 mos
0 20 40 60 80
0
50
100
months
Percentsurvival
0 20 40 60 80
0
50
100
Months
Percentsurvival
7. Common Adverse Events
Toxicity Grade N (%)
Injection site reaction 1-2 10 (45.5)
Skin induration 1-2 7 (31.8)
Pain / Pain in extremity 1 6 (27.3)
Pruritus (local) 1-2 6 (27.3)
DecreasedWBC (transient) 3-4 6 (27.3)
Decreased Plts (transient) 3-4 4 (18.2)
Erythema Multiforme 1 3 (13.6)
Flushing 1-3 3 (13.6)
Two discontinued therapy (after #2 and #4)
1- Related G3 bone pain, dyspnea and flushing
2-G3 rash and flushing
2 (9.0)
8. GPS induces immunologic responses
• Immunologic correlative data available in 14 of 22 (64%) of patients
• CD4+ Response :
‒ Four of 9 patients (44%) had a + proliferation
‒ No clear correlation with HLA-DR type
• CD8+ Response :
– Testing restricted to HLA- A02 patients
• Six of 7 patients (86%) had a CD8+ response
– IFN-γ ELISPOT
» 5 /5 (100%) positive
– WT1-A / Ao2o1 tetramer
» 4/5 (80%) positive
– Both tests
» 3/3 (100%) positive
12. Immune response (IR) after WT1 vaccination
Status DFS OS
Negative IR n= 5 15 (8.5-38.1) 50.5 (15-62.5)
Positive IR (CD4 or CD8) n= 9 Not reached (9-78.8) Not reached (15-78.5)
Survival in months: median (range)
DFS OS
P=NS P=NS
13. Conclusions
• Serial vaccination with galinpepimut-S can be accomplished
in the post-remission setting with acceptable toxicity
• Immune responses can be elicited after 6 vaccinations
– CD4+ responses seen across HLA-Class II subtypes
– Specific CD8+ responses seen in patients with HLA-A0201
• Prolonged median overall survival (62.5 mos) seen in a subset
of patients
– Trend toward improved clinical outcomes in immunologic
responders
• Upcoming multicenter randomized clinical trial planned to
establish clinical efficacy
14. Acknowlegements
• MSKCC Leukemia Service
‒ O.Abdel-Wahab
‒ E. Berman
‒ R Brentjens
‒ S Chung
‒ D Douer
‒ V Klimek
‒ R Levine
‒ M Mauro
‒ J Park
‒ R Rampal
‒ D Scheinberg
‒ A Shih
‒ E Stein
‒ MTallman
• Research Staff
– Y Bernal
– S Chanel
– R Zhang
– JWolchok
• Scheinberg Lab
‒ T. Dao
‒ T Korontsvit
‒ V Zakhaleva
• Molecular Pathology
– M Arcila
– C Hedvat
• Sellas Life Sciences
– A Gutierrez
– L Katz
• MSKCC Tetramer Core
– JYuan
• CUMC Leukemia Service
– J Jurcic
– M Frattini
– T Rosenblat
