This document provides an overview of multiple myeloma, including its definition, clinical presentation, workup, staging, management, and treatment regimens. Key points include:
- Multiple myeloma is a malignant neoplasm of plasma cells that accumulate in the bone marrow, leading to bone destruction.
- Workup involves blood and urine tests, bone marrow biopsy, skeletal survey, and imaging to determine disease severity and stage according to the Durie-Salmon or ISS staging systems.
- Treatment may include chemotherapy, steroids, immunomodulators, stem cell transplantation, and supportive care. The goal of initial therapy is to achieve remission prior to stem cell transplantation in eligible patients.
Chronic myelogenous leukemia (CML) - pluripotential stem cell disease
A malignancy the treatment of which has been revolutionised over the last decade.
Here is a comprehensive discussion on the disease
Multiple myeloma(MM) is hematologic malignancy characterized by neoplastic proliferation of single clone of plasma cell in bone marrow engaged in production of monoclonal (M) protein.
Chronic myelogenous leukemia (CML) - pluripotential stem cell disease
A malignancy the treatment of which has been revolutionised over the last decade.
Here is a comprehensive discussion on the disease
Multiple myeloma(MM) is hematologic malignancy characterized by neoplastic proliferation of single clone of plasma cell in bone marrow engaged in production of monoclonal (M) protein.
Plasma cell disorders is a difficult topic where most residents and students confuse with regarding to differentiating between various types of para-proteinemias or plasma cell dyscrasias. This simple presentation will highlight the key points in differentiating, diagnosing these orders. Initial management principles are discussed as well.
Advancements in Cancer Research with Special Reference to Pathogenesis and Di...Rahul Kadam
Cancer is a major human and animal health problem worldwide and is the second leading cause of death in the world wide. Over the past 30 years .significant progress has been achieved in understanding the molecular basis of cancer. The accumulation of this basic knowledge has established that cancer is a variety of distinct disease and that defective gene cause this disease. Further gene defect are diverse in nature and can involve either loss or gain of gene function.
Recurrent Ca Endometrium Vaginal Interstitial.pptxSadia Sadiq
a case of recurrent endometrial cancer with vaginal involvement where free hand needle placement resulted in adequate target coverage and excellent response.
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
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
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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!
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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.
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.
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.
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
5. 1)Monoclonal Gammopathy of Unknown
Significance (MGUS)
Accumulation of bone marrow plasma cells derived from
a single abnormal clone
Monoclonal Immunoglobulin Level ≤3 g/dL.
and/or
Bone marrow colonal plasma cells<10%.
No related organ or tissue impairment or symptoms.
6. 2)“Smoldering” Asymptomatic Myeloma
Monoclonal Immunoglobulin Level ≥ 3 g/dL.
and/or
Bone marrow colonal plasma cells> 10%.
No related organ or tissue impairment or symptoms.
Intermediate form of myeloma.
7. 3)Multiple Myeloma
Monoclonal Immunoglobulin Level ≥ 3 g/dL.
and/or
Bone marrow colonal plasma cells> 10%.
Plus requires one of following (CRAB Criteria).
Calcium Elevation (>11.5mg/dl).
Renal insufficiency (creatinine > 2mg/dl).
Anemia (Hb < 10g/dl or 2g/dl<normal).
Bone disease (lytic or Osteopenic).
8. 4)Solitary Plasmacytoma of Bone
Solitary bone lesion due to plasma cell tumor.
Normal Skeletal Survey.
Normal Bone marrow plasmacytosis.
No Anemia, Hypercalcemia or Renal disease.
Preserved levels of uninvolved immunoglobulins.
9. 5)Plasma cell leukemia
A very rare variant of MM, where the proliferation
of plasma cells is not confined to the bone marrow
but may be detected in the peripheral blood.
It carries a very poor prognosis with median
survival of only 3 to 6 months.
10. Multiple myeloma
MM is a malignant neoplasm of monoclonal
plasma cells that accumulate in bone
marrow,leading to bone marrow destruction
and marrow failure.
Accounts for 15% of all hematologic cancers.
12. Etiology and risk factors
No predisposing factors for the development of
multiple myeloma have been confirmed.
Environment
o Radiation exposure
o Occupational exposure (agricultural, chemical,
metallurgical, rubberplant, pulp, wood and paper
workers, and leather tanners).
o Chemical exposure to formaldehyde, epichlorohydrin,
hair dyes, paint sprays, and asbestos
13. Cytogenetics
DNA aneuploidy is observed in more than
90%;predominantly hyperdiploid, with less than
10% being hypodiploid.
Specific chromosomal abnormalities have been
identified in patients with MM involving
Translocations eg..t(11;14)t(4;14)t(14;16),
Deletions eg..chromosome 13,17p13
Amplifications..chromosome 1
15. Pathophysiology
Interactions between multiple myeloma cells and their microenvironment allow myeloma cells to
survive, grow, migrate, and resist apoptosis induced by traditional chemotherapies.These effects are
partially mediated through adhesion-mediated signalling and partly through various cytokines,
including IL-6,VEGF, IGF-1,TNF-α.
The molecular signals mediating the proliferative effects include the MAPK pathway, whereas the P13
kinase pathway provides cell survival and drug resistance signals.
Improved understanding of these interactions and the molecular mechanisms mediating them has
allowed the evaluation of novel therapies that directly target multiple myeloma cells as well as act
on the bone marrow microenvironment and other milieus, including cortical bone.
18. The initial work-up
1) History and Physical Examination
2) CBC and Peripheral Blood Smear.
3) Routine serum chemistry (e.g., calcium, blood
urea nitrogen, creatinine,albumin).
4) Bone marrow aspirate and trephine biopsy or
biopsy of mass if solitary lesion
Clonality, immunophenotype and cytogenetic
studies, plasma cell labeling index to assess
plasmacytosis.
19. Bone marrow
Bone marrow examination usually reveals an increased number of
plasma cells(>10%). Immaturity of the plasma cells is evident with
the presence of prominent nucleoli (“myeloma cells”).
These cells are strongly positive for CD38, CD138, and
cytoplasmic immunoglobulin.
Myeloma cells are negative for CD5, CD19, and surface Ig (sIg)
expression.
The pattern of bone marrow involvement in plasma cell myeloma
may be macrofocal. As a result, plasma cell count may be normal
when an aspirate misses the focal aggregates of plasma cells that
are better visualized radiographically.
20. Work- up…
M-Protien Assessment
Serum protein electrophoresis and
immunofixation to define protein type.
Serum free light chain.
24-hour urine protein, electrophoresis, and
immunofixation .
Quantitative serum Ig levels.
22. Work-up…
Prognostic Factors
• Cytogenetics by FISH
• Beta-2-microglobulin .
• Serum albumin.
• C reactive protein (CRP).
• Lactate dehydrogenase (LDH) levels.
PET/CT scan.
MRI is an excellent tool for evaluation of spinal cord
compression/impingement
24. Normal plasma cells help
protect the body from germs
and other harmful substances
Myeloma cells make
antibodies called M proteins
and other proteins. These
proteins can collect in the
blood, urine, and organs
25. Monoclonal proteins
IgG (60%).
IgA (20%).
IgD (2%).
IgE (< 0.1%).
light-chain κ or λ only (18%).
Biclonal < 1% of patients.
Nonsecretory disease < 5%.
26. Staging
Either the Durie-Salmon system at diagnosis
or the International Staging System (ISS),
which is determined at the time systemic
therapy is begun
The Durie-Salmon staging system better
provides information on tumor burden,
whereas the ISS staging system better serves
as a prognostic indicator.
33. 1)MGUS
Benign or a premalignant condition .
The risk of transformation has been estimated at 1% per
year
The long period of stability supports annual monitoring
with serum electrophoresis and blood counts.
Recent studies indicate that the diagnosis of
symptomatic multiple myeloma is typically preceded by
monoclonal gammopathy for 2 or more years.
34. 2)Smoldering Myeloma
Smoldering myeloma generally progresses to
multiple myeloma at the rate of 10% per year for
the first 5 years, 3% per year for the next 5 years,
and then 1% for the next 10 years.
35. 3)Management of Solitary Plasmacytoma
Consists of radiation therapy (at least 45 Gy).
Surgery should be considered for structural instability of
bone or rapidly progressive neurologic compromise such
as spinal cord compression.
RT is still indicated due to a high likelihood of
microscopic residual disease. Surgery alone without RT
leads to an unacceptably high local recurrence rate.
36. Management..RT
For the spine, inclusion of two vertebral bodies
above and below the grossly involved vertebra(e)
is a common practice.
Prophylactic regional nodal coverage is not
necessary in solitary plasmacytoma of bone as
multiple studies have found a very low risk of
regional nodal failure.
37. Follow-up
Over 60-75% of patients with solitary bone tumor
progressed to myeloma in 10 yrs , at a median of 2
to 3 years after treatment.
The M-protein is measured every 3 to 6 months as
indicated.
Radiologic skeletal survey is performed annually
or when symptoms develop.
38. 4)Solitary extramedullary plasmacytoma
Of all solitary extramedullary plasmacytomas, 90%
occur in the head and neck,and produce local
compressive symptoms.
If complete surgical excision can be achieved with
minimal morbidity, it may be curative, and postoperative
RT is not recommended(Soutar et al., 2004).
Incomplete excision is an indication for radical RT. Local
lymph nodes are only included in the target volume if they
are clinically involved.
39. 5)Multiple MyelomaTreatment
The main options for therapy include:
Chemotherapy.
Immune modulating treatments such as
thalidomide (Thalomid®),lenalidomide (Revlmid®),
and bortezomib (Velcade®).
Corticosteroids such as prednisone or
dexamethasone.
Stem cell (bone marrow) transplantation.
40. When to start treatment?
Once symptoms develop,
treatment with one or more of the
options discussed above is
recommended for almost all
patients
41. Choice of initial therapy
The choice of initial therapy
depends on eligibility for high-dose
therapy (HDT) and autologous
stem cell transplantation (ASCT).
42. Is stem cell transplantation an option?
Because of the risk of toxic and even fatal
complications related to stem cell
transplantation, not everyone with multiple
myeloma is a candidate for stem cell
transplantation.
Eligibility varies across countries and across
institutions
43. Eligibility Criteria For Stem cell
transplantation
In most European countries
<65 years of age.
In most centers in the United States,
Patients with following factors are NOT considered eligible for transplantation:
Age >77 years
Direct bilirubin >2.0 mg/dL
Serum creatinine >2.5 mg/dL
ECOG performance status 3 or 4 unless due to
bone pain
NewYork Heart Association functional status
Class III or IV
44. Eligibility Criteria For Stem cell
transplantation
However, these factors are guidelines; the
decision regarding transplant eligibility
should be made by the patient and physician
after discussing the potential risks, benefits,
and the needs and wishes of the patient
45. Types ofTransplant
Autologous transplantation: the stem cells are obtained from the
individual with multiple myeloma. Most commonly recommended.
Allogeneic transplantation: the stem cells or bone marrow are obtained
from a donor with a tissue type matching that of the patient. This type
of transplantation carries very high risks and is not recommended for
most individuals with multiple myeloma.40% mortality rate.
Syngeneic transplantation: the stem cells or bone marrow are obtained
from an identical twin of the individual. This is the optimal form of
transplantation although few people with multiple myeloma have an
identical twin who can serve as a donor.
46.
47. DelayedTransplantation.
Alternatively, after stem cell collection standard
chemotherapy with melphalan (or similar drugs)
given to achieve a plateau phase.
At the time of relapse, high doses of melphalan (or
similar drugs) are given.
The previously collected stem cells are returned to
the patient.
48. TandemTransplant
Double autologous transplantation (two
consecutive autologous transplantations)
may be more effective than single autologous
transplantation if the first transplant has
not produced a complete or near complete
response. The second transplantation is
usually performed within six months of the
first.
49. Effectiveness
About 1 to 2 percent of individuals die from
complications related to transplantation.
However, compared with chemotherapy
alone, autologous stem cell transplantation is
more likely to produce a response, and is
associated with 12-month longer survival
compared to chemotherapy alone.
(approximately 57 versus 44 months)
53. Bor/Dexa
• IFMTrial
• Bor/Dexa vs
VAD
• n=482
• ORR 78 v 62%
• CR 14 v 6 %
• VGPR 37 v 15
%
Bor/Thali/Dexa
• GIMEMATrial
• Bor/Th/Dex vs
Th/Dex
• n =480
• ORR 94 %
• CR 31 vs 11 %
Lena/Dexa
• SWOGTrial
SO232
• ECOG E4A03
• ORR 82-85 %
• CR 4-22 %
Primary InductionTherapy forTransplant Candidates
54. The dose-limiting side effects
Thalidomide:VTE,peripheral neuropathy,somnolence .
Lenalidomide ..VTE and thrombocytopenia.
bortezomib..Increased risk of Herpez Virus Infection,neuropathy
and hematosuppression
55.
56. MPV
• Most Efficacious
• VISTATrial
• MP vs MPB
• n=682
• 13% reduced risk of
death
• Median OS 56 vs 43
months
MPT and MPL
• IFM01-01
• MP vs MPT
• n =232
• Median OS 44 vs 29
months
• Median PFS 24 vs 18
months
• E1A06
• MPT vs MPL
• No difference in
RR,PFS and OS
Lena/Dexa
• FIRSTTrial
• Lena/Dexa vs MPT
• n = 1623
• 28 % reduction in risk
of progression or death
Primary InductionTherapy for Non-Transplant Candidates
58. High-dose therapy following induction
therapy
Consolidation with high-dose therapy after induction therapy
improves the response rate as well as event-free and overall
survival, especially in good-risk patients.
In a randomized trial reported from Italy, induction with VTD,
followed by tandem transplantation and then consolidation with
VTD followed by steroid maintenance, resulted in a very high
complete response rate of 58%, 3-year progression-free survival of
68%, and overall survival of 86%, with clear superiority to
thalidomide and dexamethasone (TD) as a comparator.
59. Consolidation Regimen
A high-dose alkylating agent, most commonly
melphalan at 200 mg/m2 with peripheral blood stem
cell support, is a standard conditioning regimen.
Addition of total-body irradiation (TBI) does not
improve the outcome.
Interestingly, in a randomized study, Fermand et al
have confirmed an equivalent survival benefit
between up-front high-dose therapy vs high-dose
therapy as a salvage regimen at relapse following
initial induction therapy.
61. Plateau phase
Chemotherapy is usually continued until multiple
myeloma enters a stable (plateau) phase.
The plateau phase is reached when the myeloma becomes
stable and shows no signs of progressing.
Although this phase is usually temporary, it typically lasts
six months or longer.
Occurs in about one half of individuals after
chemotherapy.
Achieving this phase usually requires at least six or more
cycles of treatment.
62. Thalidomide
• Cat 1
• IFM 99-06
• n =597
• Thal vs
Thal/Pamidria vs
Observation after
ASCT
• Superior EFS and
OS
Lenalidomide
• Cat 1
• CALGB 100104
• n =460
• Lena vs Placebo
• TTP 46 vs 27
months
• MM-015
• n -459
• Improved PFS 66
% compared to
placebo
Bortezomib
• Cat 2a
• UPFRONT study
Remission maintenanceTherapy
63. Refractory and relapsed disease
Approximately 10% to 15% of patients with
newly diagnosed multiple myeloma are
unresponsive to induction therapy.
Moreover, virtually all patients who respond
initially will relapse.
64. Treatment Options
Conventional chemotherapy
Alkylating agents, alone or in combination, have
been effective in approximately one-third of patients
withVAD-refractory disease.
Thalidomide
Thalidomide has an established role in therapy for
refractory/relapsed multiple myeloma, with 30% of
patients achieving at least 50% reduction in
paraprotein levels. Remissions obtained are durable
65. Treatment Options
High-dose chemotherapy
High-dose melphalan and stem cell rescue should be
offered to patients who have deferred the transplant
initially.
Novel agents
Lenalidomide
Lenalidomide has greater potency than does
thalidomide.
Bortezomib
66. FDA Approvals
In February 2012, pomalidomide (Pomalyst) was approved by
the FDA to treat patients with relapsed or refractory multiple
myeloma who have received at least two prior therapies,
including lenalidomide and bortezomib.
The phase II clinical trial that led to the approval showed a
7.4% ORR in patients treated with pomalidomide alone, and a
29.2% ORR in patients treated with pomalidomide plus low-
dose dexamethasone.
69. Supportive care
Bedrest
Bisphosphonates
(Pamidronate, 90 mg IV over >2 hours, or Zoledronic acid, 4 mg IV over 15
minutes) given monthly are indicated for all patients with stage II or III MM (and
perhaps stage I as well)
Hydration Patients must be repeatedly reminded to drink 2 to 3 L of liquids
daily to promote urinary excretion of light chains, calcium, and uric acid.
Infections are the foremost cause of death in patients with MM(Due to lack of
opsonization). Infections must be investigated and treated urgently. IVIG therapy
should be considered in cases of recurrent, life-threatening infections
70. PalliativeTreatment:Role of EBRT
The most common use of RT in the
management of plasma cell tumors is for
palliative treatment of bony disease (relief of
compression of spinal cord cranial nerves, or
peripheral nerves).
It has been estimated that approximately 40%
of patients with multiple myeloma will require
palliative RT for bone pain at some time
during the course of their disease
71. Role of EBRT
When RT is given for pain due to disease
involving a long bone, a local field suffices. It
is unnecessary to treat the entire bone .
Doses of 10 to 20 Gy (in five to 10 fractions)
are effective, although the pain relief is often
partial .
72.
73. Corrected Calcium
[4 - plasma albumin in g/dL] X 0.8 + serum Ca
For every 1-g/dL drop in serum albumin below 4 g/dL,
measured serum calcium decreases by 0.8 mg/dL. Therefore, to
correct for an albumin level of less than 4 g/dL, one should add
0.8 to the measured value of calcium for each 1-g/dL decrease
in albumin. Without this correction, an abnormally high serum
calcium level may appear to be normal.
74. Management in Renal Failure
The treatment of impaired kidney function is aimed at the specific
underlying cause.
Treatment usually includes:
intravenous fluids
Prednisone can indirectly lower blood calcium levels.
Allopurinol, a drug that can lower blood levels of uric acid.
Adequate Hydration
They should also avoid using NSAIDs and contrast media
Some patients may be candidates for hemodialysis treatment
75. Regimes Used In Renal Failure
Thalidomide/Dexa
VAD
Valcade /Dexa
Linilidamide/Dexa
76.
77.
78. A multicenter study suggested that a longer
fractionated regimen (30 Gy in 10 fractions or
higher) was associated with better neurologic
recovery than 20 Gy in five fractions or a
single 8 Gy fraction
79. For the spine, inclusion of two vertebral
bodies above and below the grossly involved
vertebra(e) is a common practice. As this is
based on relapse patterns seen following RT
for spinal metastases for solid tumors rather
than plasmacytomas, it may not be directly
applicable to solitary plasmacytoma.
80. Several studies have demonstrated durable
local control in >85% of tumors <5 cm with 35
to 40 Gy, and there is little evidence that
higher doses are necessary for small tumors,
regardless of bone or EMP locations. In
contrast, plasmacytomas >5 cm have worse
local control (90,117), and doses of 45 to 50
Gy are recommended in these bulkier
tumors, which also tend to be EMPs