Mutiple Myeloma management notes from training!
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Martha Q. Lacy, MD
Professor of Medicine
Division of Hematology
Mayo Clinic College of Medicine
Rochester, Minnesota
At diagnosis, if patient had no high-risk molecular
markers and excellent renal function. In this setting, at Mayo, we
prefer to start with lenalidomide and dexamethasone because it has high
remission rates, is oral, well tolerated, and unlikely to induce
peripheral neuropathy. When using lenalidomide in patients
with no personal history of VTE, we favor prophylaxis with aspirin at
325 mg daily. We would use IV bisphosphonates monthly for 12 months and
quarterly for 1 additional year. In patients with low-risk disease, we consider
risks and benefits of maintenance therapy. If maintenance therapy is
chosen, consider limiting the duration to 12-24 months.
At relapse, if our patient had a good response and a long
duration of remission (> 12 months), we favor re-introduction of the
initial regimen. If the patient has suboptimal response or a short
remission duration, we would change the class of drug used (eg, if
initially treated with an immunomodulatory agent [thalidomide,
lenalidomide], we would switch to proteasome inhibitor [bortezomib,
carfilzomib]. If initially treated with a proteasome inhibitor, we would
switch to an immunomodulatory agent). In this particular case, we would
need to factor in that the patient now has renal failure and a new bone
lesion. We generally re-introduce bisphosphonates quarterly at relapse
in patients with new bone lesions. However, since this patient has renal
failure, we would wait for renal improvement and favor pamidronate over
zoledronic acid with a reduced dose of 30 mg (from 90 mg).
1
Also due to the renal status of this patient, full-dose lenalidomide
should not be used. I would favor switching to bortezomib because it can
be used at full dose. However, dose-adjusted lenalidomide is also an
option.
2 A second ASCT may also be considered, especially if the initial remission was extremely long (eg, > 4 years).
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SECOND OPINION
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Thomas G. Martin III, MD
Clinical Professor of Medicine
Multiple Myeloma Translational Initiative
UCSF Medical Center, University of California, San Francisco
San Francisco, California
References
- 1 McCarthy PL, et al. N Engl J Med. 2012;366(19):1770-1781.
- 2 Attal M, et al. N Engl J Med. 2012;366(19):1782-1791.
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tougher case
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Martha Q. Lacy, MD
Professor of Medicine
Division of Hematology
Mayo Clinic College of Medicine
Rochester, Minnesota
This patient has intermediate/high-risk molecular markers consisting of the t(4;14), high beta-2 microglobulin,
and a short duration of response following ASCT. Patients with the
t(4;14) translocation have high response rates to bortezomib, so we
prefer starting with a bortezomib-based regimen. If no maintenance
therapy is given after the ASCT, remission duration is generally short.
In addition, we would prefer bortezomib-based maintenance therapy for
this patient. The choice to use bortezomib, 1 dose every other week, as
maintenance is based on the HOVON-65/GMMG-HD4 trial that showed patients receiving bortezomib maintenance had improved PFS and OS.1 Since
the remission was a fairly short duration (< 12 months), we at Mayo
favor switching class to an immunomodulatory agent-based regimen. A
second ASCT generally would not be performed if the first remission was
less than 12 months.
This patient is now dual refractory, and historical outcomes
for this patient type are poor. Data by Kumar and colleagues found that
in 286 multiple myeloma patients refractory to bortezomib and relapsing following, refractory
to, or ineligible to receive lenalidomide or thalidomide, the median OS
was 9 months and median event-free survival was only 5 months.2 Recently, carfilzomib
was approved for patients who have failed at least 2 prior therapies
including bortezomib and an immunomodulatory agent. In a phase II trial
of heavily pre-treated myeloma, carfilzomib monotherapy resulted in 20%
overall response rate with a 7.4-month median duration of response in
214 bortezomib and lenalidomide refractory/intolerant patients. In
addition to carfilzomib, a clinical trial would also be a reasonable
approach for this patient.3 Agents in late stage trials
include combination therapy and the immunomodulatory agent,
pomalidomide, which produced a 26-29% response rate in patients
refractory to both bortezomib and lenalidomide.4 Alkylating agents may also be considered for this dual refractory patient.
During treatment, Mrs Anderson developed peripheral
neuropathy. There are a number of ways to reduce the risk of
treatment-induced peripheral neuropathy. The randomized French trial
found that subcutaneous bortezomib is not inferior to IV bortezomib and
significantly reduced the risk of peripheral neuropathy.
5 Efficacy with carfilzomib monotherapy is comparable to that of bortezomib but the risk of PN is greatly reduced.
3,6
Regimens containing melphalan or cyclophosphamide may be active and
would not contribute to PN. Thalidomide can cause treatment-induced
neuropathy and would not be an option to reduce the risk of neuropathy.
Thomas G. Martin III, MD
Clinical Professor of Medicine
Multiple Myeloma Translational Initiative
UCSF Medical Center, University of California, San Francisco
San Francisco, California
Mrs Anderson initially presented with high-risk disease based on high beta-2 microglubulin,
complex cytogenetics, and FISH (+) for t(4,14). She was appropriately
treated with a bortezomib-containing regimen and went on to receive an
ASCT. Unfortunately, she relapsed within 1 year of transplant, which
suggests very aggressive disease and poor OS. She was treated
appropriately with salvage RVD but only enjoyed remission for
approximately 5 months. At this point, one could consider using
carfilzomib since the patient has received 2 prior regimens including
both an immunomodulatory agent and proteasome inhibitor. Data recently
published in Blood suggests an anticipated response rate of 23.7% and median duration of response of approximately 8 months.1
A clinical trial would also be an excellent option for this patient.
Aggressive chemotherapy including alkylator-based therapy like hyperCAD
or PACE could also be considered in a robust patient.
Elizabeth Bilotti, MSN, RN, APN
Martha Q. Lacy, MD
Elizabeth Bilotti, MSN, RN, APN
Katherine Sanvidge Shah, PharmD, BCOP
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