Consensus Panel 1:
Guidelines for Bone Disease
IMW 2011
Use of BPs in MGUS
ˇ Guidelines for the use of bisphosphonates in
MGUS are not yet clear except for patients with
osteoporosis.
ˇ Dexa's should be considered for patients with
MGUS or SMM because of the reported
increase in skeletal related events in these
patients.
ˇ If the Dexa shows osteoporosis (T score<2)
consider treating in a similar manner as patients
with osteoporosis.
BPs in SMM
ˇ For low and intermediate risk SMM, if
osteoporosis is identified by Dexa, consider
treating with bisphosphonates as for
osteoporosis.
ˇ For high risk SMM and if one can not differentiate
between MMrelated versus agerelated bone
loss, providers should consider using dosing and
schedule of bisphosphonates as for symptomatic
myeloma, especially in patients with abnormal
MRIs.
Plasmacytoma
ˇ If solitary plasmacytomano BP therapy is
indicated.
ˇ If osteoporosis is present then treat as
osteoporosis.
ˇ If multiple plasmacytomastreat like MM
MM without lytic bone lesions
ˇ It is still unclear if bisphosphonates should be
used in patients without bone lesions.
ˇ The MRC IX trial demonstrated benefit of
zoledronate in patients without bone disease.
ˇ MM with diffuse osteopenia and active
myeloma use bisphosphonates as
recommended by the ASCO guidelines for
myeloma bone disease.
BP's in patients with
MM and bone lesions
ˇ IV bisphosphonates are preferred based on
MRC IX trial which showed the superiority of
zoledronate over an oral bisphosphonate.
ˇ The Nordic trial compared 30 mg versus 90 mg
of pamidronate IV in 500 newly diagnosed
MM patients and found these doses to be
equivalent. Low dose treatment with
zoledronate has not been shown to be
effective in MM.
Frequency and Duration of BPs
ˇ No data yet available to warrant changing q 3
4 week schedule for IV BPs.
ˇ There is no randomized prospective data on
using bisphosphonates beyond two years.
Consideration for discontinuing
bisphosphonates after 2 years should be
based on an assessment of risk and benefit by
the treating physician.
Monitoring Toxicity of BPs
ˇ It is clear that dental screening prior to starting
bisphosphonates and maintaining good dental hygiene
while on bisphosphonates decreases the incidence of
ONJ.
ˇ The current practice is to stop bisphosphonates for 90
days before and after invasive dental procedures (tooth
extraction, dental implants and surgery to the jaw).
Other dental procedures do not require holding BPs.
There are no randomized prospective data
demonstrating that holding bisphosphonates for three
months impacts the development of ONJ.
Monitoring toxicity of BPs
ˇ Providers should ask patients about dental procedures
every month when the creatinine is checked.
ˇ Creatinine should be checked prior to each
administration of IV BP.
ˇ The risk for development of atypical femoral fractures
that has been reported in patients with osteoporosis
on very long term oral bisphosphonates is extremely
low and the association has not been confirmed.
ˇ Metatarsal fractures in 6 patients on long term BPs
have been reported recently.
Antimyeloma effects of BPs
ˇ There is emerging data that bisphosphonates
have antimyeloma activity both in vitro and in
patient studies.
ˇ Their use as a single agent for their anti
myeloma activity is not indicated.
Use of Vitamin D and Calcium
ˇ 60% of Myeloma patients are Vit D deficient
or insufficient.
ˇ It is very important that patients be calcium
and vitamin D sufficient.
ˇ Calcium supplementation should be used with
caution in patients with renal insufficiency.
Use of New Agents
ˇ There are a variety of new agents in
development to block osteoclastic bone
resorption or stimulate bone formation
Denosumab, an Activin A receptor antagonist,
antiDKK1 etc. Current data on these agents
are not adequate to recommend their routine
use.
Surgery for MM Bone Disease
ˇ The CAFÉ study has shown that kyphoplasty is an
effective and safe treatment that reduces pain
and improves function.
ˇ The role of vertebroplasty for myeloma patients
is less clear. Case series have reported benefits of
vertebroplasty. Two randomized trials have failed
to show a benefit of vertebroplasty compared to
sham operation for patients with osteoporotic
fractures. No similar randomized data is available
for myeloma.
Radiotherapy
ˇ Radiotherapy for local disease control and palliation
should be used judiciously and sparingly depending
on patient's presentation, need for urgent response,
and prior treatment history and response.
ˇ It should be limited as much as possible to spare the
patient's marrow function.
ˇ Current novel agents work rapidly and should
decrease the need for palliative XRT.