Bone Disease in Myeloma
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Washington DC
August 8, 2009
Washington, DC
Bone Disease in Myeloma
Lytic Lesions
Spikep
Biology of Myeloma Vascular Microenvironment Lymphocytes/ Macrophages/ Hematopoietic Cytokines Hormones
Cells/ DNA/ RNA
p / / Chemicals Microbes Myeloma Cells Neuro Nor-adrenaline Bone osteoclasts/ osteoblasts/ matrix
Other organs – Liver/ lymphatic/ brain… matrix
Bone Lesions in Myeloma
80% of patients have:
Lytic lesions and/or Diffuse osteoporosis
Bone lesions cause:
Bone lesions cause:
Pain
Fractures Fractures
Pressure on nerves/spine
I i bl d l i
Diagnosis of Bone Lesions
X-ray: full skeletal survey
X ray: full skeletal survey
CT scan or MRI
Whole body CT/PET
Bone density
Bone turnover studies, e.g.
Bone Disease Classification
Based upon Focal Lesions on X-ray
Staging With FDG-PET and CT
FL PET & MRI
Multiple Myeloma FDG PET:
Severe Diffuse (D) and Focal (F) Disease
FL on PET & MRI: Severe Diffuse (D) and Focal (F) Disease
F F F F D D D D F F F F D D D D D D FF D D MRI – STIR weighted of thoracic spine FDG PET scan of thoracic spine
Serial PET Shows Early Response
X-ray January
JAN APRIL JUNE
MRI M-protein T1 STIR MRI November January April
MRI-CR “lags” Behind Clinical Response
Incidence of nCR/CR and Incidence of MRI-CR
Patients with 1+ Baseline FL detectable by PET and by MRIPET Shows Earlier Evidence of Responsey y
80% 100%
60% 80%
PET & actual
MRI 40% 12-Month 0% 20% MRI-CR nCR/CR Events / N 12 / 59 33 / 59 12 Month Estimate 17% 61% P<0.001 0% 0 6 12 18 24
Months After Starting VAD
Treatment for Bone Disease
Treat the myeloma
Treat the myeloma
Chemotherapy Radiation
Radiation
Treat the bone
Bisphosphonates Bisphosphonates Calcium/Vitamin D S ti Supportive care Kyphoplasty
Radiotherapy
May be useful in specific
it ti
situations
Pain control Pain control
Spinal cord compression
Prevent or treat pathologic fractures
However, radiation damages
normal marrow
normal marrow
Vertebroplasty
Balloon Kyphoplasty: A Minimally
Invasive Fracture Reduction Procedure
KyphX Introducer Tool
Kit KyphX IBT inflation:R d th f t
KyphX IBT Removal:
• Leaves a defined cavity
Kit:
• Allows precise,
minimally invasive access to the vertebral body.
P o ides o king
• Reduces the fracture. • Compacts the bone. • May elevate endplates
• Leaves a defined cavity
and trabecular dam that can be filled with an
approved bone void filler of the physician’s choice
• Provides working
channel
Balloon Kyphoplasty Case Studyyp p y y
Patient: 61 YO Female
Diagnosis: g Multiple Myelomap y
Fracture Reduced: T11, L2, 1 ½ yrs old
Lieberman and Reinhardt Study Myeloma Patient Outcomes: Pain Improvement
Visual Analog Scale Visual Analog Scale
6.18 7 0 ) 4 5 6 P a in (0 to 1 0 2.84 2 3 4 S el f-R a te d P 0 1 pre-op post-op Me a n S 0 = no pain pre op post op
Source: Lieberman and Reinhardt. Clinical Orthopaedics and Related Research. 2003;415(S):176-186.
Bisphosphonates
Primary Therapy
for myeloma
Primary Therapy
for myeloma
bone disease to reduce skeletal
related events (SREs)
related events (SREs)
Recommended
as ongoing
therapy for all myeloma patients
with bone disease
Bisphosphonate Use Guidelines
Starting BP Duration of therapy Duration of therapy Choice of BP R l i Renal issues Dental evaluationSee both Mayo and IMWG Guidelines See both Mayo and IMWG Guidelines
Starting Bisphosphonates
Lesions on x-ray? Yes or No? Lesions on x ray? Yes or No?
Positive findings on MRI and/or CT PET?
MRI: > 7 lesions and/or progression/ pain MRI: > 7 lesions and/or progression/ pain PET: high SUV; CT abnormal
R d d b i l d it ?
Reduced bone mineral density? Urinary NTX increased?
Duration of Bisphosphonates
Not indefinite
Minimum 2 years
Can consider stopping early if > VGPR Can consider stopping early if > VGPR
AND
N ti b di
No active bone disease
Stop or reduce frequency at 2 years if
no active bone disease
Stopping versus Reduced
Dose/ Schedule
Consider both renal/ ONJ issues
No data on Q2 or 3 months
Clinical trials needed
Clinical trials needed
Choice of Bisphosphonate
Consensus that “efficacy equivalent” for Consensus that efficacy equivalent for
available drugs:
Aredia (Pamidronate)( )
Zometa (Zoledronic Acid)
Concern that there is higher risk of toxicities
with Zometa
Jaw osteonecrosis and renal toxicity both potential issues
issues.
BUT toxicities preventable with proper awareness … BUT toxicities preventable with proper awareness
Current Bisphosphonates
Aredia Aredia 90 mg over 2-4 hrs. monthly Zometa Zometa4 mg over 15-45 minutes monthly
Questions:
I f i ti
Infusion times
Time to Onset of Osteonecrosis in Myeloma 25% 36-Month Zometa vs Aredia 20% 25% Zometa Aredia Events / N 10 / 211 10 / 413 36 Month Estimate 10% 4% P = .002
15% Data censored at 36 months
5% 10% 0% 5% 0 12 24 36 0 12 24 36
Management Recommendations for ONJ
Before starting bisphosphonates (BP)
Dental evaluation/ treatment Dental evaluation/ treatment
While On BP
Regular dental care/ check-upsegu a de ta ca e/ c ec ups
Avoid dental extraction/ procedures Review type/ schedule of BP with MD
d k “d h l d ”
? Reduce Frequency or take “drug holiday”
Established ONJ
Antibiotics Antibiotics
Minor dental procedures
Rinses/ supportive measurespp Stop BP Rx to allow healing Possible hyperbaric 02
New Approaches to Enhance Osteoblast Activity and Heal Bones
Activity and Heal Bones
