The document summarizes the best approaches to treating newly diagnosed multiple myeloma based on patient fitness level and risk profile. For fit patients, phase 3 trials show superior outcomes with bortezomib-containing triple-drug induction regimens followed by stem cell collection and autologous stem cell transplant compared to doublet regimens. For unfit patients, bortezomib-melphalan-prednisone or lenalidomide-low dose dexamethasone are standard first-line options. High-risk patients with genomic abnormalities may benefit from enrollment in clinical trials or bortezomib-containing consolidation/maintenance therapies with consideration of autologous stem cell transplant.
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.
According to my research, the best combined treatments for MM are botrezomib and thalidomide. Targeting the proteasome inside myeloma cells looks to be the most efficient way to fight this type of cancer
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.
According to my research, the best combined treatments for MM are botrezomib and thalidomide. Targeting the proteasome inside myeloma cells looks to be the most efficient way to fight this type of cancer
Role of Flow Cytometric Immunophenotyping in Plasma Cell DyscrasiasApollo Hospitals
Immunophenotyping is being routinely used for the diagnosis of leukemias. With the advent of specific markers for plasma cells, it has become possible to differentiate between benign and malignant plasma cells based on their immunophenotypic profile. The enhanced use of immunophenotyping in plasma cells dyscrasias may help to categorize the borderline cases which can not be done with morphology alone. Also the immunophenotypic profiling of plasma cells would help in Minimal Residual Disease (MRD) evaluation of patients on treatment of multiple myeloma (MM).
SEMINAR PRESENTATION ON CONTRAST INDUCED NEPHROPATHY BY PHARM D STUDENT
IT INCLUDES COMPLETE OVERVIEW OF THE TOPIC CIN.
POST CONTRAST ACUTE KIDNEY INJURY( PC-AKI) WITH TREATMENT AND MANAGEMENT.
Cells respond to nutrient deprivation a variety of ways. In addition to global down regulation of cap-dependent protein
synthesis mediated by the GCN2 and mTO RC1 signaling pathways, a catabolic process autophagy is upregulated to
provide internal building blocks and energy needed to sustain viability. It has recently been shown that during nutrient
deprivation tRNAs accumulate in the nucleus, but the functional role of this accumulation remains unknown. This study
investigates whether subcellular localization of tRNAs plays a role in signaling nutritional stress and autophagy. We report
that human fibroblasts that accumulate tRNA in the nucleus due to downregulation of their transportin, Xpo-t, show
reduced mTO RC1 activity and upregulated autophagy. This suggests that sub-cellular localization of tRNAs may regulate
an unicellular response to starvation independently of the cellular nutritional status.
Genetics of attention deficit hyperactivity disorder (adhd)Joy Maria Mitchell
Attention deficit hyperactivity disorder (ADHD) is a developmental disorder. ADHD is the commonly studied and
diagnosed as psychiatric disorder. Here we shall see the relation between extraversion and ADHD, neuroticism,
biological relation, Environmental factors and with diagnosis of ADHD. It is known that Genetics is one of the factors
that may contribute to, or exacerbate ADHD. Recent research probing towards the environmental and Genetic factors
causing ADHD differences is the main source for investigation
L’électrophorèse en champ pulsé est le résultat de la combinaison d’une digestion par des enzymes de restriction à faible nombre de sites de coupure et d’une électrophorèse adaptée à la grande taille des produits de digestion. Le résultat est un profil de restriction intéressant tout le génome du microorganisme
Real-World Treatment Patterns in Relapsed/Refractory Multiple Myeloma Patient...Howard Friedman
Goal: To describe patient characteristics, treatment patterns, and survival outcomes in RRMM patients with at least two prior lines of therapies, including lenalidomide (LEN), and at least one PI, in the real-world setting in Turkey.
Luciano J. Costa, MD, PhD, prepared useful Practice Aids pertaining to multiple myeloma for this CME activity titled "Exploring Clinical Decisions in the New Era of Myeloma Management: The Impact of Novel Platforms and Agent Classes Across the Spectrum of Care." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2Dypn7b. CME credit will be available until March 12, 2020.
Describes the emerging resistance of epithelial cancer of the ovary to current therapies and the role of PARP inhibitors in the management in view of the recent drug approvals.
Expert Guidance on Current Standards and New Directions in Newly Diagnosed Mu...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.
Presented by leading expert Urvi Shah, MD, Assistant Attending in the Myeloma Service at Memorial Sloan Kettering Cancer Center, this slide deck will explore guidance on current standards and new directions in newly diagnosed multiple myeloma.
STATEMENT OF NEED
An estimated 35,730 new cases of multiple myeloma are diagnosed in the United States annually, and 12,590 people die of the disease (Siegel et al, 2023). Characterized by clonal proliferation of malignant plasma cells in the bone marrow, multiple myeloma is associated with anemia, renal insufficiency, bone destruction, and hypercalcemia, all of which significantly impact patients’ quality of life. The development of novel therapies and combinations in recent years, including anti-CD38 antibodies, has provided numerous therapeutic options for newly diagnosed multiple myeloma. However, the optimal selection of induction therapy and subsequent treatment sequencing for individual patients remains a challenge. Additionally, factors including age, frailty, comorbidities, transplant eligibility, treatment-related toxicities, and supportive care needs complicate treatment decisions (Costello et al, 2022). This hematology/oncology fellows lecture series will explore expert guidance on current standards and new directions in newly diagnosed multiple myeloma.
TARGET AUDIENCE
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with multiple myeloma.
LEARNING OBJECTIVES
Upon completion of this activity, participants should be able to:
Assess guideline-recommended treatment combination and sequencing strategies in NDMM
Evaluate the role of minimal residual disease (MRD) assessment in NDMM treatment
Review the mechanism of action, efficacy, and safety of anti-CD38 monoclonal antibodies in the treatment of NDMM
Discuss strategies to monitor and manage treatment-related toxicities and optimize survivorship care
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
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
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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
1. Best approach to newly
diagnosed multiple myeloma
Elisabet Manasanch M.D., M.H.Sc.
Assistant Professor, Department of Lymphoma/Myeloma
Division of Cancer Medicine
4. Overview
103,826 new cases
72,453 deaths
worldwide
Incidence rate
3-5/100,000
Kihyun Kim et al. Clinical profiles of multiple myeloma in Asia – An Asian Myeloma Network Study. 2014. AJH.
JH Lee et al. Multiple myeloma in Korea: past, present, and future perspectives. 2010. Int J Hematol.
Blacks
Age 70 years
Incidence rate
0.5-3/100,000
Age 62 years
5. Overview
Plasma cell malignancy – molecular heterogeneity
Natural history progression from MGUS/SMM
Evidence of end-organ damage
GROUPS Associated translocations
7 -> MF t(14;16) and t(14;20)
6 -> CD-2
CCND1/CCND3
t(11;14) and t(6;14) activating
Cyclin D 1 and Cyclin D3
5 -> CD-1
CCND1/CCND3
t(11;14) and t(6;14) activating
Cyclin D 1 and Cyclin D3
4 -> HY Hyperdiploidy
3 -> MS t(4;14), activation of FGFR3 and
MMSET
2 -> LB
Low Bone
Underexpression of DKK1
1 -> PR
PRoliferation
Increased proliferation index
Zhan et al. The molecular classification of multiple myeloma. Blood. 2006 / Lohr et al. Widespread genetic heterogeneity in multiple myeloma:
Implications for targeted therapy. Cancer Cell. 2014.
6. Treatment History
Dex VAD Thal+Dex CTD VD PAD Rd VTD RVD CRd
Melphalan/
prednisone
High-dose therapy with
autologous stem cell
HD dexamethasone
VAD
HD melphalan
Autologous BM
transplants
support
Lenalidomide
Thalidomide
Bortezomib
Carfilzomib
Pomalidomide
Elotuzumab
Daratumumab
100
80
60
40
20
0
Sarcolysine
1958 1962 1983-86 1996 1999 2003 2006 2012
Patients with ≥ VGPR (%)
S Kumar et al. Cancer Treatment Reviews 2010; Korde et al. ASH 2013.
7. Overview
DIAGNOSTIC APPROACH
Blood CBC with differential
Complete chemistries
LDH
Serum quantitative immunoglobulins
SPEP/IFE
Serum β2-M and albumin
Serum free light chain assay
Urine 24 hour UPEP/IFE
Pathology/Molecular Bone marrow biopsy (core and aspirate – unilateral)
Metaphase cytogenetics
FISH
BM aspirate flow cytometry
Gene expression profiling*
Imaging Skeletal survey
MRI/PETCT
RA Kyle and SV Rajkumar. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009. Manasanch
et al. Flow cytometric sensitivity and characteristics of plasma cells in patients with multiple myeloma or its precursor disease: influence of biopsy site
and anticoagulation method. Leukemia and Lymphoma. 2014. In press.
9. Fit patients
Absence of comorbidities, even if advanced age
IFM 2005/01 GIMEMA HOVON-GMMG PETHEMA/GEM
Harousseau
VD vs VAD
(n= 240 vs 242)
JCO 2010
Cavo
VTD vs TD
(n=241 vs 239)
Blood 2012
Sonneveld
PAD vs VAD
(n=417 vs 416)
JCO 2012
Rosinol
VTD vs VBCMP/VBAD+V
vs TD
(n=130 vs 129 vs 127)
Blood 2012
Results post-ASCT
CR
(nCR+sCR)
40% vs 18.4% 73.1% vs 60.9% 31% vs 15% 46% vs 38% vs 24%
PFS (months) 36 vs 29.7 (S) NR vs 32 35 vs 28 (S) 56.2 vs 35.5 vs 28.2 (S)
OS (months)
Not reached (32
months follow up)
90% vs 88% at 3
years
Not reached (66
months follow up)
74% vs 70% vs 65% (4
years) (NS)
Most patients are treated with ASCT
Phase III trials with bortezomib induction regimens
10. Combinations novel agents
Phase II studies with small numbers of patients
VRD
CyBorD
Richardson et al. Lenalidomide, bortezomib and dexamethasone combination therapy in patients with newly diagnosed mutiple
myeloma. Blood. 2010. / Reeder et al. Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed
Multiple myeloma: high response rates in a phase II clinical trial. Leukemia. 2009.
11. Combinations novel agents
Randomized phase II study EVOLUTION (140 patients)
8 x 3 week cycles initial therapy followed by 6-week cycles of bortezomib maintenance
Small numbers of patients
PFS at one year: 86 vs 83 vs 93 vs 100 (%)
OS at one year: 94% vs 100% in all other arms
S Kumar et al. Randomized, multicenter, phase 2 study(EVOLUTION). Blood. 2012
12. CRd in newly diagnosed MM
Jakubowiak et al
(Phase I/II, n = 53)
Korde et al
(Phase II, n = 45)
Combination
therapy
CRd (Phase II Cfz 20/36 mg/m2)
8 cycles
CRd (Cfz 20/36 mg/m2)
8 cycles
Extended
dosing
CRd (Cfz every other week) 16 cycles, off-protocol
Ln at last tolerated dose d1-21
after 16 cycles
Ln 10 mg d1-21,
24 cycles
Transplant ≥PR stem cell collection, HDM optional Stem cell collection
Jakubowiak et al
(Phase I/II, n = 53)
Korde et al
(Phase II, n = 45)
ORR
62% nCR/CR, 81% VGPR, 98% PR after 12
cycles
51% CR/nCR, all MRD
negative (without ASCT)
PFS 92% (at 24 months) 97% (at 12 months)
A Jakubowiak et al. A phase ½ study of carfilzomib in combination with lenalidomide and low-dose dexamethasone
as a frontline treatment for multiple myeloma. Blood. 2012 / N Korde et al. Phase II Clinical and Correlative Study of
Carfilzomib, Lenalidomide, and Dexamethasone Followed by Lenalidomide Extended Dosing (CRD-R) Induces High Rates
of MRD Negativity in Newly Diagnosed Multiple Myeloma (MM) Patients. ASH abstract 538. 2013.
13. New agents in NDMM
RANDOMIZED PHASE 3 STUDIES
1.- IFM/DFCI: RVD with upfront or delayed autologous stem cell
transplant
2.- RVD vs CRd
EARLY PHASE TRIALS
1.- Carfilzomib, cyclophosphamide, dexamethasone
2.- Carfilzomib, bendamustine, dexamethasone
3.- Ixazomib, lenalidomide, dexamethasone
4.- Ixazomib, cyclophosphamide, dexamethasone
5.- RVD+ panabinostat
6.- Cyclophosphamide, lenalidomide, dexamethasone
15. Velcade as initial treatment in newly diagnosed
myeloma not eligible for transplant
Randomized, international, phase III trial of VMP vs MP in 682 previously untreated patients
with symptomatic MM who were not candidates for HDT-ASCT due to age (≥65 yrs) or
co-morbid conditions
VMP
Cycles 1–4
Bortezomib 1.3 mg/m2 IV: d 1,4,8,11,22,25,29,32
Melphalan 9 mg/m2 and prednisone 60 mg/m2:
d 1–4
Cycles 5–9
Bortezomib 1.3 mg/m2 IV: d 1,8,22,29
Melphalan 9 mg/m2 and prednisone 60 mg/m2:
d 1–4
MP
Cycles 1–9
Melphalan 9 mg/m2 and prednisone 60 mg/m2:
d 1–4
R
A
N
D
O
M
I
Z
E
9 x 6-week cycles (54 weeks) in both arms
• Primary end
point: TTP
• Secondary end
points: CR rate,
ORR, time to
response
J San Miguel et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. NEJM. 2008
16. VISTA trial
Time to progression Overall survival
VMP: 24.0 months
MP: 16.6 months
P < .000001
100
80
60
40
20
0
VMP
MP
Time (months)
Median follow-up: 25.9 months
3-year OS:
VMP: 72%
MP: 59%
P = .0032
VMP
MP
Time (months)
0 3 6 9 12 15 18 21 24 27
100
80
60
40
20
0
0 4 8 12 16 20 24 28 32 36 40
682 patients
RR: 71% VMP versus 35% MP
Rate of CR: 30% VMP versus 4% MP
J San Miguel et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. NEJM. 2008
17. HD vs LD lenalidomide. ECOG E4A03
Four 28-day cycles
1-yr OS 2-yr OS
HD/lenalidomide 87% 75%
LD/lenallidomide 96% 87%
Transplant-eligible
patients can
proceed to SCT
Continue therapy until
disease progression
Lenalidomide + High-Dose Dexamethasone (RD)a
Len: 25 mg/day, days 1-21
Dex: 40 mg/day, days 1-4, 9-12, 17-20
(n = 223)
Lenalidomide + Low-Dose Dexamethasone (Rd)
Len: 25 mg/day, days 1-21
Dex: 40 mg/day, days 1, 8, 15, 22
(n = 222)
Rajkumar et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as
initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2010.
21. High risk MM
Genomic abnormalities
FISH
- del 17p
- t(14:16)
- t(14:20)
GEP
- High risk signature
Laboratory abnormalities
Renal failure
Circulating plasma cells
Increased LDH or B2M
Moreau et al. Combination of International Scoring System 3, High Lactate Dehydrogenase, and t(4;14)
and/or del(17p) Identifies Patients With Multiple Myeloma (MM) Treated With Front-Line Autologous
Stem-Cell Transplantation at High Risk of Early MM Progression–Related Death. JCO. 2014
22. High risk MM
* Bortezomib containing regimens as initial treatment
* Use of bortezomib consolidation/maintenance
* Use of ASCT as consolidation
* Explore tandem ASCT
* Enroll in clinical trials if this is a possibility
AK Nooka et al. Consolidation and maintenance therapy with lenalidomide,
bortezomib and dexamethasone (RVD) in high-risk myeloma patients. Leukemia. 2014.
23. Conclusions
* Fit patients:
*3 drug combination as initial therapy.
*Stem cell collection and evaluation for ASCT.
* Unfit patients:
*VMP (other MPR, MPT)
*Rd continuous treatment
* High risk patients:
*Refer for clinical trials
*Use bortezomib (proteasome inhibitors) in
consolidation/maintenance
*Evaluate for ASCT/tandem ASCT
24. MDACC Myeloma Center
Dr. Robert Orlowski
Dr. Jatin Shah
Dr. Donna Weber
Dr. Sheeba Thomas
Dr. Michael Wang
Dr. Parmar
Dr. Qazilbash
Dr. Shah
Dr. Bashir
Stem Cell Transplant Department
Support staff, nurses, coordinators
Patients
Editor's Notes
Reeder: Thirty-three newly diagnosed, symptomatic patients with MM
received bortezomib 1.3 mg/m2 intravenously on days 1, 4, 8
and 11, cyclophosphamide 300 mg/m2 orally on days 1, 8, 15
and 22 and dexamethasone 40 mg orally on days 1–4, 9–12 and
17–20 on a 28-day cycle for four cycles.
All patients undergoing stem cell harvest
Richardson:
Abstract
This phase 1/2 study is the first prospective evaluation of lenalidomide-bortezomib-dexamethasone in front-line myeloma. Patients (N = 66) received 3-week cycles (n = 8) of bortezomib 1.0 or 1.3 mg/m2 (days 1, 4, 8, 11), lenalidomide 15 to 25 mg (days 1-14), and dexamethasone 40 or 20 mg (days 1, 2, 4, 5, 8, 9, 11, 12). Responding patients proceeded to maintenance or transplantation. Phase 2 dosing was determined to be bortezomib 1.3 mg/m2, lenalidomide 25 mg, and dexamethasone 20 mg. Most common toxicities included sensory neuropathy (80%) and fatigue (64%), with only 27%/2% and 32%/3% grade 2/3, respectively. In addition, 32% reported neuropathic pain (11%/3%, grade 2/3). Grade 3/4 hematologic toxicities included lymphopenia (14%), neutropenia (9%), and thrombocytopenia (6%). Thrombosis was rare (6% overall), and no treatment-related mortality was observed. Rate of partial response was 100% in both the phase 2 population and overall, with 74% and 67% each achieving very good partial response or better. Twenty-eight patients (42%) proceeded to undergo transplantation. With median follow-up of 21 months, estimated 18-month progression-free and overall survival for the combination treatment with/without transplantation were 75% and 97%, respectively. Lenalidomide-bortezomib-dexamethasone demonstrates favorable tolerability and is highly effective in the treatment of newly diagnosed myeloma. This study is registered at http://clinicaltrials.gov as NCT00378105.
had a successful collection. Twenty-three patients underwent
stem cell transplantation (SCT) and are evaluable through day
100 with CR/nCR documented in 70% and XVGPR in 74%.
VRD:
Bz 1.3 1,4,8,11
Dex 40 mg weekly
Cyclophosphamide 500 mg/m2 days 1 and 8 and 15 in vdc-mod
Vdcr len 15 mg 1-14
Vdr len 25 mg 1-14
VMP
Cycles 1–4
Bortezomib 1.3 mg/m2 IV: d 1,4,8,11,22,25,29,32
Melphalan 9 mg/m2 and prednisone 60 mg/m2:
d 1–4
Cycles 5–9
Bortezomib 1.3 mg/m2 IV: d 1,8,22,29
Melphalan 9 mg/m2 and prednisone 60 mg/m2:
d 1–4
MP
Cycles 1–9
Melphalan 9 mg/m2 and prednisone 60 mg/m2:
d 1–4
This ECOG trial is well recognized for determining that dexamethasone dosing of 40 mg/day on a 4-days-on, 4-days-off schedule is too high. This randomized trial of lenalidomide and dexamethasone compared the then-standard dosing of dexamethasone to a once-weekly dosage of 40 mg and found that survival was significantly improved in the low-dose dexamethasone arm -- 1-year OS was 87% with len/high-dose dex vs 96% with len/low-dose dex.
Objective: to assess if a reduced dose of dex decreases toxicity while maintaining efficacy
Primary endpoint: ORR after first 4 cycles
aBased on the superiority of the Rd regimen, the study was stopped at a median follow-up of 12.5 months and patients in the RD arm crossed over to Rd therapy.
* Half of the patients start with VMP and half with Rd.
Treatment duration: 74 weeks