Guidelines Index
Multiple Myeloma TOC
Discussion, References
Practice Guidelines
in Oncology – v.3.2010
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NCCN Clinical Practice Guidelines in Oncology™
Multiple
Myeloma
V.3.2010
www.nccn.org
Guidelines Index
Multiple Myeloma TOC
Discussion, References
Practice Guidelines
in Oncology – v.3.2010
Version 3.2010, 04/20/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
NCCN
®
NCCN Multiple Myeloma Panel Members
George Somlo, MD † ‡ Þ
City of Hope Comprehensive Cancer Center
Keith Stockerl-Goldstein, MD †
Siteman Cancer Center at Barnes-Jewish
Hospital and Washington University School
of Medicine
Guido Tricot, MD, PhD ‡
Huntsman Cancer Institute at the University
of Utah
Julie M. Vose, MD ‡
UNMC Eppley Cancer Center at the
Nebraska Medical Center
Donna Weber, MD † ‡ Þ
The University of Texas M. D. Anderson
Cancer Center
Joachim Yahalom, MD §
Memorial Sloan-Kettering Cancer Center
Furhan Yunus, MD
St. Jude Children’s Research
Hospital/University of Tennessee Cancer
Institute
�
�
* Cristina Gasparetto, MD †
Duke Comprehensive Cancer Center
Carol Ann Huff, MD †
The Sidney Kimmel Comprehensive Cancer
Center at Johns Hopkins
Madan Jagasia, MD ‡
Vanderbilt-Ingram Cancer Center
Bruno C. Medeiros, MD ‡
Stanford Comprehensive Cancer Center
Ruby Meredith, MD, PhD §
University of Alabama at Birmingham
Comprehensive Cancer Center
Noopur Raje, MD † ‡
Dana-Farber/Brigham and Women’s Cancer
Center | Massachusetts General Hospital
Cancer Center
Jeffrey Schriber, MD ‡
City of Hope Comprehensive Cancer Center
Seema Singhal, MD ‡
Robert H. Lurie Comprehensive Cancer
Center of Northwestern University
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�
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Kenneth C. Anderson, MD/Chair ‡
Dana-Farber/Brigham and Women's
Cancer Center | Massachusetts General
Hospital Cancer Center
Melissa Alsina, MD ‡
H. Lee Moffitt Cancer Center & Research
Institute
William Bensinger, MD †
Fred Hutchinson Cancer Research
Center/Seattle Cancer Care Alliance
J. Sybil Biermann, MD ¶
University of Michigan Comprehensive
Cancer Center
Asher Chanan-Khan, MD †
Roswell Park Cancer Institute
Adam D. Cohen, MD
Fox Chase Cancer Center
Steven Devine, MD
The Ohio State University Comprehensive
Cancer Center - James Cancer Center and
Solove Research Institute
Benjamin Djulbegovic, MD , PhD † ‡
H. Lee Moffitt Cancer Center & Research
Institute
�
�
†
† Medical oncology
‡ Hematology
Bone marrow transplantation
¶ Surgery/Surgical oncology
§ Radiotherapy/Radiation oncology
€ Pediatric oncology
* Writing committee member
�
Þ Internal medicine
Multiple Myeloma
NCCN Guidelines Panel Disclosures
Guidelines Index
Multiple Myeloma TOC
Discussion, References
Practice Guidelines
in Oncology – v.3.2010
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Discussion
References
Table of Contents
Multiple Myeloma:
Waldenström’s Macroglobulinemia:
NCCN Multiple Myeloma Panel Members
Guidelines Index
Print the Multiple Myeloma Guidelines
Summary of Guidelines Updates
Osseous or Extraosseous Solitary Plasmacytoma: Primary Treatment (MYEL-2)
Multiple Myeloma: Induction Therapy and Follow-up (MYEL-3)
Definition of Multiple Myeloma (Smoldering and Active Myeloma) (MYEL-B)
Systemic Light Chain Amyloidosis (AL-1)
Workup and Primary Treatment (WALD-1)
Surveillance and Follow-up (WALD-2)
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Diagnostic Workup and Clinical Presentations (MYEL-1)
Follow-up and Surveilliance (MYEL-4)
Active Disease: Additional Treatment for Progression (MYEL-6)
Staging Systems for Multiple Myeloma (MYEL-A)
Response Criteria for Multiple Myeloma (MYEL-C)
Induction Therapy (MYEL-D)
Adjunctive Treatment (MYEL-E)
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These guidelines are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment.
Any clinician seeking to apply or consult these guidelines is expected to use independent medical judgment in the context of individual clinical
circumstances to determine any patient's care or treatment. The National Comprehensive Cancer Network makes no representations nor warranties
of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. These
guidelines are copyrighted by National Comprehensive Cancer Network. All rights reserved. These guidelines and the illustrations herein may not
be reproduced in any form without the express written permission of NCCN. ©2010.
Clinical Trials:
Categories of Evidence and
Consensus:
NCCN
All recommendations
are Category 2A unless otherwise
specified.
See
The
believes that the best management
for any cancer patient is in a clinical
trial. Participation in clinical trials is
especially encouraged.
NCCN
To find clinical trials online at NCCN
member institutions, click here:
nccn.org/clinical_trials/physician.html
NCCN Categories of Evidence
and Consensus
Multiple Myeloma
This section of
the guideline is
being updated.
Guidelines Index
Multiple Myeloma TOC
Discussion, References
Practice Guidelines
in Oncology – v.3.2010
Version 3.2010, 04/20/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
NCCN
®
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Summary of the Guidelines Updates
UPDATES
Multiple Myeloma
Summary of major changes in the 1.2010 version of the NCCN Multiple Myeloma Guidelines from the 2.2009 version include :
Initial Diagnostic Workup
Unilateral bone marrow aspirate + biopsy, added “including bone marrow immunohistochemistry and /or bone marrow flow cytometry.”
Deleted C-reactive protein from the “Useful under some circumstances” column.
Footnote g: Added the IFM 99-03 trial where no overall survival or progression free survival advantage was seen with autologous transplant
followed by mini allograft in high-risk myeloma patients (Garban et al, Blood 2006; 107:3474).
NCCN Categories of Evidence and Consensus were revised on the following therapies:
Primary induction therapy for transplant candidates:
Bortezomib/dexamethasone category 1 previously category 2B
Bortezomib/doxorubicin/dexamethasone category 1 previously category 2B
Bortezomib/thalidomide/dexamethasone category 1 previously category 2B
Dexamethasone category 2B previously category 2A
Thalidomide/dexamethasone category 2B previously category 2A
Primary induction therapy for non-transplant candidates:
Dexamethasone category 2B previously category 2A
Lenalidomide/low-dose dexamethasone category 1 previously category 2B
Thalidomide/dexamethasone category 2B previously category 2A
Vincristine/doxorubicin/dexamethasone (VAD) category 2B previously category 2A
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MYEL-1
MYEL-4
MYEL-D
�
�
�
Lenalidomide/dexamethasone category 1 previously category 2B
Liposomal doxorubicin/vincristine/dexamethasone (DVD) category 2B previously category 2A�
�
Summary of major changes in the 3.2010 version of the NCCN Multiple Myeloma Guidelines from the 2.2010 version include:
Summary of major c
Single agent lenalidomide was added as an option for maintenance therapy with a footnote.
The new footnote: “Lenalidomide as maintenance has been evaluated in three independent randomized clinical trials. Results from each of
these trials show improvements in TTP. The panel felt that this warranted inclusion however this recommendation remains Category 2A since
these results have not undergone full peer review and safety/efficacy data are still preliminary.”
The Discussion section has also been updated.
MYEL-D
�
�
�
�
hanges in the 2.2010 version of the NCCN Multiple Myeloma Guidelines from the 1.2010 version include:
The addition of the updated section.Discussion
Guidelines Index
Multiple Myeloma TOC
Discussion, References
Practice Guidelines
in Oncology – v.3.2010
Version 3.2010, 04/20/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
NCCN
®
See Primary
Treatment
(MYEL-3)
MYEL-1
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
�
�
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H&P
CBC, differential, platelets
BUN/creatinine, electrolytes
Skeletal survey
Unilateral bone marrow aspirate +
biopsy, including bone marrow
immunohistochemistry and/or bone
marrow flow cytometry
LDH
Calcium/albumin
microglobulin
24 h urine total protein
Serum quantitative immunoglobulins,
serum protein electrophoresis (SPEP),
serum immunofixation electrophoresis
(SIFE)
24 h urine for total protein, urine protein
electrophoresis (UPEP), urine
immunofixation electrophoresis (UIFE)
�
�
�
Beta-2
Cytogenetics
FISH [del 13, del 17, t(4;14), t(11;14),
t(14;16)]
a
b
c
d
Includes Durie-Salmon Stage l myeloma.
See Staging Systems for Multiple Myeloma (MYEL-A).
Smoldering AsymptomaticSee Myeloma ( ) (MYEL-B).
See Active Myeloma (Symptomatic) (MYEL-B).
CLINICAL
PRESENTATION
Smoldering
(a )symptomatic b,c
Active
(symptomatic)d
Solitary
plasmacytomaa
See Osseous:
Primary Treatment
(MYEL-2)
See Extraosseous:
Primary Treatment
(MYEL-2)
Useful Under Some Circumstances
�
�
�
�
�
MRI for suspected
compression
CT scan (avoid contrast)
Tissue biopsy to diagnose a solitary
osseous or extraosseous plasmacytoma
�
�
�
�
�
PET/CT scan
Bone densitometry
Plasma cell labeling index
Staining of marrow and fat pad for
amyloid
Serum free light chain assay
Serum viscosity
HLA typing
vertebral
INITIAL DIAGNOSTIC WORKUP
Multiple Myeloma
Guidelines Index
Multiple Myeloma TOC
Discussion, References
Practice Guidelines
in Oncology – v.3.2010
Version 3.2010, 04/20/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
NCCN
®
MYEL-2
Solitary
Osseous
Solitary
Extraosseous
RT ( 45 Gy) to
involved field
�
RT ( 45 Gy) to
involved field
and/or surgery
�
Restage
with
myeloma
workup
See Active
(symptomatic)
(MYEL-3)
Primary
progressivee
or
Response
followed by
progressione
e .See Response Criteria for Multiple Myeloma (MYEL-C)
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
CLINICAL
PRESENTATION
PRIMARY
TREATMENT
FOLLOW-UP/SURVEILLANCE
�
�
�
�
�
�
�
�
CBC
Serum chemistry for creatinine,
albumin, LDH, calcium, beta-2
microglobulin
Consider serum free light chain
assay
24 h urine for total protein, urine
protein electrophoresis (UPEP),
urine immunofixation
electrophoresis (UIFE)
Consider bone marrow biopsy as
clinically indicated
Consider bone survey as clinically
indicated or annually
Consider MRI and or CT and or
PET/CT as clinically indicated or
every 6-12 mo
Serum quantitative
immunoglobulins, serum protein
electrophoresis (SPEP), serum
immunofixation electrophoresis
(SIFE)
Multiple Myeloma
Guidelines Index
Multiple Myeloma TOC
Discussion, References
Practice Guidelines
in Oncology – v.3.2010
Version 3.2010, 04/20/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
NCCN
®
MYEL-3
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Observe at 3-
6 mo intervals
(category 1)
See Active (symptomatic)
Myeloma below
Progression to stage II
or higher diseasee
Induction therapy ,
bisphosphonates
+ adjunctive
treatment
as indicated
f
g
g Response
e
No
responsee
Stem-cell harvest
(adequate for 2
transplants), if
candidate for
transplantation
(Refer for evaluation
by stem cell transplant
center)
See
Additional
Treatment
(MYEL-4)
See
Additional
Treatment
(MYEL-6)
a
b
f
g
c
d
Includes Durie-Salmon Stage l myeloma.
e
See Staging Systems for Multiple Myeloma (MYEL-A
Smoldering
See Active (Symptomatic) Myeloma (MYEL-B)
).
.
See (Asymptomatic) Myeloma (MYEL-B
See Response Criteria for Multiple Myeloma (MYEL-C
See Myeloma Therapy (MYEL-D
See Adjunctive Treatment (MYEL-E
).
).
).
).
CLINICAL
PRESENTATION
INDUCTION
THERAPY
FOLLOW-UP/SURVEILLANCE
Smoldering
(a )symptomatic b,c
Active
(symptomatic)d
�
�
�
�
�
Quantitative immuno-
globulins + quantitation
of M protein
CBC, differential, platelets
BUN, creatinine, calcium
Bone survey annually or
for symptoms
Bone marrow biopsy as
clinically indicated
Consider free light chain
Consider MRI
Consider PET/CT scan
�
�
�
(serum and
urine)
Multiple Myeloma
Guidelines Index
Multiple Myeloma TOC
Discussion, References
Practice Guidelines
in Oncology – v.3.2010
Version 3.2010, 04/20/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
NCCN
®
�
�
�
�
�
Quantitative immunoglobulins + quantitation
of M protein at least every 3 mo
CBC, differential, platelets
BUN, creatinine, calcium
Bone survey annually or for symptoms
Bone marrow biopsy as clinically indicated
�
�
�
Consider free light chain
Consider MRI
Consider PET/CT scan
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Active
(symptomatic)
myeloma:
Response after
induction therapy
h
i
A prospective trial by Bruno, et al. NEJM 356:1110-1120, found improved survival for patients receiving an autologous transplant followed by non-myeloablative
allograft compared to patients who received tandem autologous grafts. The IFM trial (99-03) by Garban et al, Blood 2006; 107:3474, reported no overall survival or
progression free survival with autologous transplant followed by mini allograft in high-risk myeloma patients. Allogeneic stem cell transplant may include
nonmyeloablative (mini) following autologous stem cell transplant or fully myeloablative on a clinical trial (off-trial category 3).
Single autologous transplantation: Category 1 evidence supports proceeding straight after induction therapy to high dose therapy and stem cell transplant versus saving
the stem cell transplant for salvage therapy. Evidence suggests equivalent overall survival although progression free survival can be prolonged by an early transplant.
Fermand JP, Katsahian S, Divine M, et al. High dose therapy and autologous blood stem cell transplantation compared with conventional treatment in myeloma patients
aged 55 to 65 years: Long term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol 2005;23:9227-9233.
Barlogie B, Kyle RA, Anderson KC, et al. Comparable survival of patients with multiple myeloma treated with autotransplant-supported melphalan - TBI or standard
VBMCP consolidation and no role of interferon maintenance: final results of US Intergroup Trial S9321. J Clin Oncol 2006;929-936.
Renal dysfunction and advanced age are not contraindications to transplant.
2007;
Current data do not support
miniallografting alone.
j
Continue induction
therapy to plateau
Allogeneic stem cell
transplant in clinical trial
h
Autologous stem
cell transplant
i,j
OR
OR
Monitor as above and/or maintenance
therapy (clinical trial preferred)
MYEL-4
FOLLOW-UP/SURVEILLANCE
Multiple Myeloma
Post-allogeneic and
Post-autologous stem
cell transplant See
Additional Treatment
(MYEL-5)
Post-induction
therapy See
Additional Treatment
(MYEL-6)
Guidelines Index
Multiple Myeloma TOC
Discussion, References
Practice Guidelines
in Oncology – v.3.2010
Version 3.2010, 04/20/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
NCCN
®
Response or
stable disease
e
Refractory diseasee
Progressive diseasee
Observe or maintenance
therapyf
Observe
or
Second tandem transplant
or
Maintenance therapyf
Salvage therapy on or off clinical trial
or
Donor lymphocyte infusion
f
Salvage therapy on or off clinical trial
or
Allogeneic stem cell transplant on clinical trial
or
Additional autologous stem cell transplant on
clinical trial (category 2B)
f
k
Progressive diseasee
Post-allogeneic stem cell transplant:
Post-autologous stem cell transplant:
e
k
.
Allogeneic stem cell transplant may include nonmyeloablative (mini) following autologous stem cell transplant or fully myeloablative on a clinical trial (off-trial category 3).
f
Current data do not support miniallografting alone.
See Response Criteria of Multiple Myeloma (MYEL-C
See Myeloma Therapy (MYEL-D
)
).
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Progressive diseasee
MYEL-5
ADDITIONAL TREATMENT
Salvage therapy on or off clinical trial
or
Allogeneic stem cell transplant on clinical trial
(category 3 for conventional vs clinical trial)
f
k
Stable diseasee
Multiple Myeloma
Guidelines Index
Multiple Myeloma TOC
Discussion, References
Practice Guidelines
in Oncology – v.3.2010
Version 3.2010, 04/20/10 © 2010 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.
NCCN
®
ADDITIONAL TREATMENT
MYEL-6
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Active (symptomatic)
myeloma:
Progressive diseasee
Autologous stem cell transplant on or off clinical trial
Salvage therapy on or off clinical trial
or
Allogeneic stem cell transplant on a clinical trial
i
f
k
or
e
k
.
Allogeneic stem cell transplant may include nonmyeloablative (mini) following autologous stem cell transplant or fully myeloablative on a clinical trial (off-trial category 3).
.
Single autologous transplantation: Category 1 evidence supports proceeding straight after induction therapy to high dose therapy and stem cell transplant versus saving
the stem cell transplant for salvage therapy. Evidence suggests equivalent overall survival although progression free survival can b