This document presents three patient cases involving multiple myeloma with renal failure or neuropathy. Case 1 is a 59-year-old male with renal failure and a poor prognosis cytogenetic profile. Case 2 is a 36-year-old female with renal failure and deletion of 13 and 17p. Case 3 is a 72-year-old male who developed neuropathy during induction therapy. For each case, the document discusses appropriate induction regimens, transplant eligibility, maintenance therapy, and options for relapse based on the patient's specific characteristics and past treatments.
HIV Alert:Emerging Updates on Dual Therapy.2018hivlifeinfo
In this downloadable slideset, Joseph J. Eron, Jr., MD, and Babafemi Taiwo, MBBS, provide expert insight into the use of a recently-approved dual-therapy regimen and review data surrounding investigational two-drug regimens.
Format: Microsoft PowerPoint (.ppt)
File size: 375 KB
Date posted: 1/5/2018
HIV Alert:Emerging Updates on Dual Therapy.2018hivlifeinfo
In this downloadable slideset, Joseph J. Eron, Jr., MD, and Babafemi Taiwo, MBBS, provide expert insight into the use of a recently-approved dual-therapy regimen and review data surrounding investigational two-drug regimens.
Format: Microsoft PowerPoint (.ppt)
File size: 375 KB
Date posted: 1/5/2018
Robert Z. Orlowski, MD, PhD, prepared useful practice aids pertaining to multiple myeloma management for this CME/CNE activity titled "Driving Change in Multiple Myeloma: Updates on Novel Agent Classes and Next-Generation Therapeutics." For the full presentation, monograph, complete CME/CNE information, and to apply for credit, please visit us at http://bit.ly/2SPKaZZ. CME/CNE credit will be available until August 7, 2020.
Roy H. Decker, MD, PhD; Kristin Higgins, MD; and Jyoti D. Patel, MD, prepared useful practice aids pertaining to immunotherapies in lung cancer for this CME/MOC activity titled “NSCLC Tumor Board: Navigating the Evolving Role of Immunotherapy in Multimodal Management of Locally Advanced and Early-Stage Lung Cancer.” For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2mFfEWE. CME/MOC credit will be available until October 22, 2020.
Her2Neu positive breast cancer is comprises of about 15-20% of all breast cancer. Among them quite a few number of patients present as de novo metastasis . In this presentation you ll find a guide how to manage it with relevant evidences. Presentation is meant for Oncology trainees.
Robert Z. Orlowski, MD, PhD, prepared useful practice aids pertaining to multiple myeloma management for this CME/CNE activity titled "Driving Change in Multiple Myeloma: Updates on Novel Agent Classes and Next-Generation Therapeutics." For the full presentation, monograph, complete CME/CNE information, and to apply for credit, please visit us at http://bit.ly/2SPKaZZ. CME/CNE credit will be available until August 7, 2020.
Roy H. Decker, MD, PhD; Kristin Higgins, MD; and Jyoti D. Patel, MD, prepared useful practice aids pertaining to immunotherapies in lung cancer for this CME/MOC activity titled “NSCLC Tumor Board: Navigating the Evolving Role of Immunotherapy in Multimodal Management of Locally Advanced and Early-Stage Lung Cancer.” For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2mFfEWE. CME/MOC credit will be available until October 22, 2020.
Her2Neu positive breast cancer is comprises of about 15-20% of all breast cancer. Among them quite a few number of patients present as de novo metastasis . In this presentation you ll find a guide how to manage it with relevant evidences. Presentation is meant for Oncology trainees.
Marketing Research Application Assignment on behalf of Alkesh Dinesh Mody Ins...Kartik Mehta
Marketing research application assignment includes:
1. Regression and Correlation analysis
2. Cluster Analysis
3. Multidimensional Scaling
4. Discriminant Analysis
and much more..Just go through the entire PDF document
AD105 - OneUI.. really? Is that because you don't know about Twitter Bootstrap?Andrew Barickman
Did you know that Twitter Bootstrap is the most popular GitHub project? It's more popular than even rails and jQuery. If you don't know what it can do then you probably should and here is your chance. In this session I will discuss: - Building sexy web applications by leveraging the Twitter Bootstrap community - Why Twitter Bootstrap might be a better choice then IBM's OneUI - Rapid prototyping with Twitter Bootstrap - XPages specific resources to get you rolling - XPages time savers to generating valid Twitter Bootstrap markup
Metronomic Chemotherapy Vs Best Supportive Care in Progressive Pediatric Tumors.Pranav Sopory
Journaal Club discussing the Randomised Clinical Trial (RCT) of metronomic chemotherapy in extra cranial, non-hematopoietic solid malignancies in paediatric population (aged 5-18 years). Courtesy Dr Atul Batra, Asst. Prof. Medical Oncology, IRCH, AIIMS.
Optimizing Treatment Sequencing for Patients With Relapsed/ Refractory Multi...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 Shaji Kumar, MD, Professor of Hematological Malignancies
Mayo Clinic Cancer Center, offers expert insight on the assessment of MM, emerging and current therapies, cutting edge approaches to personalized treatments plans, and much more.
Aim of this ppt presentation:
To understand the standard of care for both GBM and anaplastic glioma.
To know what is the new advances and modifications to the standard of care?
Contents:
Introduction: 2 slides.
GBM:
Epidemiology: 1 slide.
Molecular biology & New trends: 5 slides
EORTC/NCIC trial: 10 slides.
MGMT: 1 slide.
Evidence-based medicine: 6 slides.
Avastin in GBM: 2 slides.
Novocure (TTF): 2 slides.
Gliadel (BCNU) wafers: 1 slide.
Anaplastic astrocytoma: 7 slides
Take home message.
Report Back from San Antonio Breast Cancer Symposium (SABCS 2022)bkling
Curious about the latest developments in Early-Stage Breast Cancer and Metastatic Breast Cancer Research? Join us as Dr. Anne Blaes, the Division Director of Hematology/Oncology/Transplantation and Professor in Hematology/Oncology at the University of Minnesota, breaks down the most recent developments released at the annual San Antonio Breast Cancer Symposium regarding early-stage and metastatic breast cancer research.
Radiotherapy and Cetuximab in head and neck cancer.pptxNamrata Das
Radiotherapy and Cetuximab in head and neck cancer
Bonner trial
RTOG 0522
TREMPLIN
RTOG 1016
De-Escalate trial
TROG
HN.6
PembroRAD
Nimotuzumab
Panitimumab
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
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.
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
2. Case 1
• 59 yr old male
• 7/2012: Dyspnea, chest pain, pain between shoulders
• 8/2012: Cardiac work-up: Stent placement
• 9/2012: Pain continued: MRI spine: T7
compression, C5-6 and C3-4 encroachment on neural
foramina
• 9/18/2012: Hospitalized for respiratory infection:
Hgb 8.3 g/dL, creatinine 2.03, Ca++ 12.3 mg/dL,
albumin 1.8 g/dL, hydrated sent home
3. Case 1
• Bone marrow 85% CD38, CD138, CD56, λ +, κ – PC
T. Protein 12.4 g/dL, Albumin 3.0 g/dL, M-protein 5.7
g/dL: IgG λ, Bence Jones Protein 1250 mg/day
Free λ 2420 mg/L Free κ 14.6 mg/L Free κ: λ 0.01
β2M 44.7 mg/L Alb 3.0g/dL: ISS stage III
• Bone survey: lytic lesions skull, ribs, T7 compression
• Hgb 10.9 g/dL, Plt 206 k/μL , WBC 7.9 k/μL, 3% plasma
cells, BUN 53 creatinine 4.69, Ca++ 13.1
mg/dL, albumin 3.0 g/dL, uric acid 13.3
• Cytogenetics: t(4;14), del 13, del 1q
4. Case 1 (Questions)
What would you do first?
2. Chemotherapy/Immunotherapy
3. Chemo/Immunotherapy + Dialysis
1. Dialysis
5. High Cut Off Hemodialysis (HCO-HD)
• 2005: 97 pts randomized to conventional therapy or conventional therapy w/ 5-7
plasma exchanges (stratified by dialysis) w/ no benefit in mortality, dialysis
dependence, or GFR < 30 ml/min at 6 mos.
Clark et al: Ann Intern Med 143: 777-84, 2005
• 2010: 27 pts MM w/ HD dependence (CrCl < 15 ml/min) 19 pts had biopsy proven
cast-nephropathy and received combination chemo and FLC removal by HCO-HD).
8 hrs/day x 5 days then 8 hrs q.o.d. x 12 days or more
13/19 pts achieved sustained reduction FLC
6 pts not achieving sustained reduction had chemo interrupted
Dialysis equally effective, difference due to FLC production rates
Uninterrupted Baseline FLC: D12 FLC = 1%
Interrupted Baseline FLC: D12 FLC = 266%
14/19 became dialysis independent
Hutchison et al: Clin J Am Soc Nephrol 4: 745-54, 2009
6. Case 1: Results With Therapy Initiation
Chemo held
temporarily due to
infection
7. Case 1 (Questions)
What would be the best induction therapy?
2. Lenalidomide and dexamethasone (once weekly)
3. Bortezomib and dexamethasone (day of and after B)
4. Bortezomib, melphalan and prednisone
5. Bortezomib, cyclophosphamide, dexamethasone
1. Thalidomide and dexamethasone (once weekly)
6. Bortezomib, lenalidomide, dexamethasone
8. Criteria for Renal Response
Reversibility of Renal Failure
Renal Response
Sustained (lasting 2 months) improvement of creatinine clearance
Complete (CRrenal)
Improvement of CrCl from < 50 ml/min to > 60 ml/min
Partial (PRrenal)
Improvement of CrCl from < 15 ml/min to 30-59 ml/min
Minor (MRrenal)
Improvement of CrCl from < 15 ml/min to 15-29 ml/min
OR
15-29 ml/min to 30-59 ml/min
Dimopoulos et al, Clin Lymphoma Myeloma 2009:9:302-6
9. Considerations for Induction Therapy Using
Novel Agents in Patients with Renal Failure
Thalidomide Lenalidomide CarfilzomibConsideration Bortezomib
No Yes No
Renal
metabolism
No
No Possible
Possible, Avo
idable
Renal Toxicity No
? ? ?
Efficacy for
Induction in
Renal Failure
?
Hyperkalemia Cytopenias None
Additional
Toxicity in
Renal Patients
None
10. CC I-B B-B
32 47 17
Parameter
n
29.2 26.9 20.6Med. CrCl (ml/min)
53 53 76%CrCl < 30ml/min
% Renal Response
59 79 94> MRrenal
41 45 71CRrenal
47 51 82> PRrenal p0.04
Roussou et al, Leukemia Research 2010:9: 1395-1397
Reversibility of Renal Failure Newly Diagnosed
1.8 1.6 0.69Med. Mos to Response p0.007
9 19.1 23.5%Renal Response
w/o MM Response
CC = Combination Chemotherapy (VAD/VAD-like, Melphalan + HD Dex)
I-B = IMiD-Based Thalidomide or lenalidomide + HD Dex +/- cyclophosphamide/melphalan
B-B = Bortezomib-based + HD Dex
12. Case 2
• 36 yr old female
• 2/2010: Rt Chest wall pain during pregnancy
Did not resolve after pregnancy
13. • 3/2010: Rt. Rib resection: + CD38 +CD56 +Kappa
Plasma cells
• 3/2010: Preoperative creatinine 0.8 mg/dL
Postoperatively 5.1 mg/dL
Dexamethasone 40 mg x 1
Transfer to MD Anderson Cancer Center
Case 2
• Hgb 7.5 g/dL, Plt 611 k/μL , WBC 10.2 k/μL, BUN 48
creatinine 4.1mg/dL, Ca++ 10 mg/dL, albumin 4.1
g/dL, uric acid 7.5, potassium 5.5 meq/L, phosphorus
5.5 mg/dL
14. Case 2
• Bone survey: Rib lesion + Small lytic lesions bilateral
femora + humeri
• Bone marrow 50% CD38, CD138, CD56, λ -, κ + PC
T. Protein 7.3 g/dL, Albumin 4.3 g/dL, M-protein
0.2 g/dL, IgG K, Bence Jones Protein 4925 mg Kappa/d
Free λ 10.4 mg/L Free κ 15,300 mg/L Free κ: λ 1471.5
β2M 9.9 mg/L Alb 4.3g/dL: ISS stage III
• Cytogenetics: Deletion 13 and Deletion 17p13.1
15. Case 2
What Would Be the Best Induction Therapy?
1. Lenalidomide and dexamethasone (once weekly)
2. Bortezomib and dexamethasone (day of and after B)
3. Bortezomib, melphalan and dexamethasone
4. Bortezomib, cyclophosphamide, dexamethasone
5. Bortezomib, lenalidomide, dexamethasone
6. Bortezomib, doxorubicin, dexamethasone (PAD)
16. Case 2
Would you proceed with myeloablative therapy
and stem cell transplant after successful
induction?
2. No
1. Yes
17. Case 2
After successful induction therapy +/-
myeloablative therapy and autologous stem cell
transplant what maintenance therapy (if any)
would you use?
2. Lenalidomide
1. None
3. Bortezomib
4. Other
25. • 4/2007-7/2007: Thalidomide + Dexamethasone
Developed Grade 2 neuropathy during induction.
Case 3
• 7/2007: HDM + AuSCT: Worsening of neuropathy.
VGPR: No Maintenance; neuropathy persists, but
improved to grade 2 without pain.
26. Case 3
What would you use for Relapse?
Thalidomide +
Dexamethasone
HDM +
AuSCT
27. Case 3
What would you use for Relapse?
2. Lenalidomide and dexamethasone (once weekly)
3. Bortezomib and dexamethasone (day of and after B)
4. Lenalidomide-based 3 drug combination
1. Thalidomide and dexamethasone (once weekly)
4. Bortezomib-based 3 drug combination
5. Carfilzomib
5. Pomalidomide + Dexamethasone
28. Study PX171-004: Phase 2 Trial of Single-agent Carfilzomib
in Relapsed and/or Refractory Multiple Myeloma
Cohort 1
20 mg/m2
Cohort 2†
20 mg/m2 cycle 1
Escalation to 27 mg/m2
in all subsequent cycles
Carfilzomib IV
QD x 2 for 3 weeks (28-day cycle for up to 12 cycles
BOR-treated*
(n=35)
BOR-naïve (n=59)
BOR-naïve (n=70)
Study Population (N=165)
• Measurable disease
• Responsive to
≥1 prior therapy
• Relapsed and/or refractory MM
following 1–3 prior treatment
regimens
• ECOG PS 0–2
Vij et al, Blood: 119(24):5661-70, 2012
ORR
(CR+VGPR+PR)
42.4% 52.2% 47.6%
CBR (ORR+MR) 59.3% 64.2% 61.9%
Cohort 1 Cohort 2 TotalBortezomib Naive
29. Cohort 1
20 mg/m2
Cohort 2†
20 mg/m2 cycle 1
Escalation to 27 mg/m2
in all subsequent cycles
Study PX171-004: Phase 2 Trial of Single-agent Carfilzomib
in Relapsed and/or Refractory Multiple Myeloma
Duration of Clinical Benefit Resp.
(med. Months)
11.5 NR
Time to Clinical Benefit Response
(med. months)
1.9 0.5
Time to Response
(med. months)
1.0 0.5
Duration of Remission
(med. Months)
13.1 NR
Median TTP
(med. Months)
8.3 NR
Vij et al, Blood: 119(24):5661-70, 2012
30. History of Neuropathy at Baseline 69.8%
Treatment Emergent Peripheral Neuropathy
(all but 1pt Gr I or II in both studies)
17.1%
Median QOL FACT-GOG No Change
Grade 1 or 2 Neuropathy at Study Entry 53%
Phase 2 Trials of Single-agent Carfilzomib
in Relapsed and/or Refractory Multiple Myeloma
15.2%
87%
PX-171-004
Bortezomib Naive
PX-171-003-A0
Bortezomib Exposed
Vij et al, Blood: 119(24):5661-70, 2012
Jagannath et al,, Clinical lymphoma, myeloma & leukemia. 12(5):310-8, 2012
31.
32. Grade 1 Neuropathy 51%
0
0
Grade 2 Neuropathy 29%
Phase 1 Trial of Pomalidomide
in Relapsed and/or Refractory Multiple Myeloma
Pomalidomide
2 mg po daily
Pomalidomide
4 mg po daily
Lacy et al, Blood 118(11): 2970-2975, 2011
Grade 3 Neuropathy
Grade 4 Neuropathy
69%
3%
0
17%
33. Low Neuropathic Novel
Agents
Elotuzumab
Doxorubicin/
Liposomal Doxorubicin*
Pomalidomide?
Bendamustine
Low Neuropathic
Conventional Agents
Steroids
Carfilzomib* Cyclophosphamide Dexamethasone
Lenalidomide Melphalan Prednisone
Potential Low Neuropathic Complications
* Combination of carfilzomib with anthracyclines has not been reported; because of potential cardiac effects
with carfilzomib this combination should be avoided based on lack of data
Use of these combinations outside a clinical trial should be limited to those with previously reported results.
34. Case 3
This Patient: Carfilzomib at Relapse
Thalidomide +
Dexamethasone
HDM +
AuSCT
Carfilzomib
35. Case 4
• 57 yr old female
• 7/2012: Right Hip X-rays show lytic lesion right femur
• Cytogenetics 46XX, FISH negative for high-risk
• Hgb 9.8 g/dL, Plt 251 k/μL , WBC 6.8 k/μL, creatinine
0.7 mg/dL, Ca++ 9.1 mg/dL, albumin 3.0
M-protein 5.3 g/dL, IgA λ, Bence Jones Protein 98
mg/day, free λ 65 mg/L free κ 1.6 mg/L free κ: λ
0.01, β2M 7.2 mg/L Alb 3.0g/dL: ISS stage III
• Bone survey: lytic lesions skull, ribs, femur
• Bone marrow 17% CD38, CD138, CD56, λ +, κ – PC
38. Case 4: What would you use for relapse?
2. Bortezomib-based 3-drug regimen
3. Myeloablative therapy and Autologous SCT
4. Allogeneic SCT
5. Clinical Trial
1. Lenalidomide-based 3-drug regimen
39. Bortezomib + High – Dose Melphalan (HDM) for Early
Transplant Relapse and High-Risk Myeloma
Wong Doo et al. Leukemia & Lymnphoma 2012; online
HDM + BORTEZOMIB
Stem Cell Harvest: Cyclophosphamide + G-CSF
(usually collected before transplant 1)
Day -2: Melphalan 200mg/M2 IV
(RI:Melphalan 140mg/M2 IV)
Day -1: Bortezomib 1.3 – 1.6 mg/M2 IV)
Day 0: Stem cells infused
Day 1 + Day 4: 2 pts Bortezomib 1.3 – 1.6 mg/M2 IV
Day 2: 12 pts: Bortezomib 1.3 – 1.6 mg/M2 IV
HDM
Stem Cell Harvest: Cyclophosphamide + G-CSF
(usually collected before transplant 1)
Day -2: Melphalan 200mg/M2 IV
(RI:Melphalan 140mg/M2 IV)
Day 0: Stem cells infused
N=16 PTS: Relapsed or Refractory 2nd
Salvage
N=16 PTS: Historical Control
Relapsed or refractory
> MR
VGPR
Med. PFS
Med. OS
Med. OS
Early relapse
81.3%
37.5%
7 mos
28 mos
14.5 mos
p 0.22
p 0.22
p 0.299
21 mos p 0.11
8 mos p 0.522
87.5%
12.5%
7 mos
40. Allogeneic Stem Cell
TransplantPFS or EFS Benefit
Overall Survival
IFM: Garban et al Blood 2006
(High-Risk del 13, B2M > 3)
No No
EFS Benefit Yes
OS Benefit
Auto – RIC Allo SCT
Vs. Auto-Auto
Italian: Bruno et al Blood 2010
(No risk stratification)
No 3yr PFS
Benefit
NoBMT CTN: Krishnan et al, Lancet Oncol
(High-Risk del 13, B2M > 3)
5Yr YesBjorkstrand et al J Clin Oncol, 2011
(High-Risk del 13, B2M > 3)
41. Allogenic hematopoietic stem‐cell transplantation with
reduced‐intensity conditioning in patients with refractory and
recurrent multiple myeloma
Shimoni et al, Cancer 116 (15): 3621-3630, 5 MAY 2010 DOI: 10.1002/cncr.25228
SCT from a female donor to a male
achievement of a CR.
occurrence of chronic GVHD
Chemoresistance at the time of SCT
Bad Risk
Good Risk
42. Myeloma Section
Robert Orlowski, MD
Raymond Alexanian, MD
Jatin Shah, MD
Sheeba Thomas, MD
Michael Wang, MD
Department of Blood
and Marrow
Transplantation
Richard Champlin , MD
Muzaffar Qazilbash, MD
Simrit Parmar, MD
Uday Popat, MD
Nina Shah, MD
Thank you to the nurses, research staff and most
importantly, the patients!