Sagar Lonial, MD, FACP, and Philippe Moreau, MD, prepared useful practice aids pertaining to multiple myeloma for this CME activity titled "Changing Perspectives on Multiple Myeloma and ASCT: Clinical Decision-Making, New Evidence, and Expanding Therapeutic Options." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/3crZvJz. CME credit will be available until March 30, 2021.

1. The Multiple Myeloma Treatment
Pyramid: Recommendations
for ASCT-Eligible Patients1
PRACTICE AID
a
Consider harvesting peripheral blood stem cells prior to prolonged exposure to lenalidomide. b
Preferred initial treatment in patients with acute renal insufficiency. Consider switching to bortezomib/
lenalidomide/dexamethasone after renal function improves. c
Optimal dosing in this regimen has not been defined. d
Can potentially cause cardiac and pulmonary toxicity, especially in elderly
patients. e
Triplet regimens should be used as the standard therapy for patients with multiple myeloma; however, elderly or frail patients may be treated with doublet regimens.
ASCT: autologous stem cell transplant; NCCN: National Comprehensive Cancer Network.
1. NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma. V.3.2020. https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Accessed March 16, 2020.
Access the activity, “Changing Perspectives on Multiple Myeloma and
ASCT: Clinical Decision-Making, New Evidence, and Expanding Therapeutic
Options,” at PeerView.com/JHF40
Other
recommended
regimens
Preferred
regimens
Useful in
certain
circumstances
Primary Therapy for Newly Diagnosed Transplant Candidates
Exposure to myelotoxic agents (including alkylating agents and nitrosoureas) should
be limited to avoid compromising stem cell reserve prior to stem cell harvest
in patients who may be candidates for transplant
Category 2A
Bortezomib/cyclophosphamide/
dexamethasoneb
Category 1
Bortezomib/lenalidomidea
/
dexamethasone
Category 2B
Ixazomib/lenalidomidea
/
dexamethasone
Category 2A
Carfilzomibc,d
/lenalidomidea
/
dexamethasone
Category 1
• Bortezomib/thalidomide/
dexamethasone
Clinical Notes
• Selected, but not inclusive of all regimens
• Herpes zoster prophylaxis for patients treated with proteasome inhibitors or daratumumab
• Subcutaneous bortezomib is the preferred method of administration
• Aspirin (81-325 mg) is recommended with immunomodulator-based therapy; therapeutic
anticoagulation is recommended for those at high risk for thrombosis
Category 2A
• Bortezomib/dexamethasonee
• Bortezomib/doxorubicin/
dexamethasone
• Carfilzomib/cyclophosphamide/
dexamethasone
• Cyclophosphamide/lenalidomidea/
dexamethasone
• Daratumumab/bortezomib/
thalidomide/dexamethasone
• Dexamethasone/thalidomide/
cisplatin/doxorubicin/
cyclophosphamide/etoposide/
bortezomib (VTD-PACE)
• Ixazomib/cyclophosphamide/
dexamethasone

2. PRACTICE AID
The Multiple Myeloma Treatment
Pyramid: Recommendations for Patients
With Relapsed/Refractory Disease1
a
Can potentially cause cardiac and pulmonary toxicity, especially in elderly patients. b
Triplet regimens should be used as the standard therapy for patients with multiple myeloma; however, elderly or
frail patients may be treated with doublet regimens. c
Clinical trials with these regimens primarily included patients who were lenalidomide-naïve or with lenalidomide-sensitive multiple myeloma.
d
May interfere with serological testing and cause false-positive indirect Coombs test. e
Consider single-agent lenalidomide or pomalidomide for steroid-intolerant individuals.
ASCT: autologous stem cell transplant; IMiD: immunomodulatory drug; MM: multiple myeloma; NCCN: National Comprehensive Cancer Network; R/R: relapsed/refractory; XPO1: exportin 1.
1. NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma. V.3.2020. https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Accessed March 16, 2020. 2. https://www.fda.gov/drugs/
resources-information-approved-drugs/fda-grants-accelerated-approval-selinexormultiple-myeloma. Accessed March 16, 2020.
Please consult NCCN guidelines for additional information regarding the regimens listed here, including summary of indications for use.
Access the activity, “Changing Perspectives on Multiple Myeloma and
ASCT: Clinical Decision-Making, New Evidence, and Expanding Therapeutic
Options,” at PeerView.com/JHF40
Other
recommended
regimens
Preferred
regimens
Useful in certain
circumstances
Therapy for Previously Treated Myeloma
(If a regimen listed here was used as a primary induction therapy and relapse is >6 mo, the same regimen may be repeated)
Category 2A
• Bendamustine/bortezomib/
dexamethasone
• Bendamustine/lenalidomide/
dexamethasone
• Bortezomib/cyclophosphamide/
dexamethasone
• Carfilzomiba
/cyclophosphamide/
dexamethasone
• Cyclophosphamide/lenalidomide/
dexamethasone
• Daratumumabd
• Daratumumabd
/carfilzomib/
dexamethasone
• Daratumumabd
/pomalidomide/
dexamethasone
• Elotuzumab/bortezomib/
dexamethasone
• Elotuzumab/pomalidomide/
dexamethasone
• lxazomib/cyclophosphamide/
dexamethasone
• Ixazomib/dexamethasoneb
• Ixazomib/pomalidomide/
dexamethasone
• Panobinostat/carfilzomiba,b
• Panobinostat/lenalidomide/
dexamethasone
• Pomalidomide/cyclophosphamide/
dexamethasone
• Pomalidomide/carfilzomiba
/
dexamethasone
Category 2A
• Bendamustine
• Carfilzomib/cyclophosphamide/
thalidomide/dexamethasone
• High-dose cyclophosphamide
• Selinexor/dexamethasone
Generally reserved for aggressive disease
• Dexamethasone/
cyclophosphamide/etoposide/
cisplatin (DCEP)
• Dexamethasone/thalidomide/
cisplatin/doxorubicin/
cyclophosphamide/etoposide
(DT-PACE) ± bortezomib (VTD-PACE)
Category 2A
• Bortezomib/lenalidomide/dexamethasone
• Carfilzomib (weekly)a
/dexamethasoneb
Category 1
• Bortezomib/liposomal
doxorubicin/dexamethasone
• Bortezomib/dexamethasoneb
• lsatuximab-irfc/pomalidomide/
dexamethasone
• Lenalidomide/
dexamethasoneb,e
• Panobinostat/bortezomib/
dexamethasone
• Pomalidomide/bortezomib/
dexamethasone
• Pomalidomide/
dexamethasoneb,e
Clinical Notes
• Selected, but not inclusive of all regimens
• Herpes zoster prophylaxis for patients treated with proteasome inhibitors or daratumumab
• Subcutaneous bortezomib is the preferred method of administration
• Aspirin (81-325 mg) is recommended with immunomodulator-based therapy; therapeutic anticoagulation is recommended for those
at high risk for thrombosis
• Consideration for appropriate regimen is based on the context of clinical relapse
• Based on results of the ICARIA-MM trial,
isatuximab was recently approved by the FDA
in combination with pom-dex, for the treatment
of adults with multiple myeloma who have
received ≥2 prior therapies, including
lenalidomide and a proteasome inhibitor.1
• XPO1 inhibitor selinexor recently approved for
use in patients with R/R MM who have received
≥4 prior therapies (including patients refractory
to ≥2 proteasome inhibitors or IMiDs and an
anti-CD38 monoclonal antibody)2
Recent updates in R/R MM
Category 1
• Carfilzomib (2 x wk)a
/
dexamethasoneb
• Carfilzomiba
/lenalidomide/
dexamethasonec
• Daratumumabd
/bortezomib/
dexamethasone
• Daratumumabd
/lenalidomide/
dexamethasone
• Elotuzumab/lenalidomide/
dexamethasonec
• Ixazomib/lenalidomide/
dexamethasonec

3. Clinical Tool for Defining MRD
Responses in Myeloma1
PRACTICE AID
a
Sustained MRD negativity when reported should also annotate the method used (eg, sustained flow MRD negative, sustained sequencing MRD negative). b
BM MFC should follow NGF guidelines. The NGF method
is an eight-color two-tube approach, which has been extensively validated. The two-tube approach improves reliability, consistency, and sensitivity, because of the acquisition of a greater number of cells. The eight-
color technology is widely available globally and the NGF method has already been adopted in many flow laboratories worldwide. The complete eight-color method is most efficient using a lyophilized mixture of
antibodies, which reduces errors, time, and costs. Five million cells should be assessed. The FCM method employed should have a sensitivity of detection of at least 1 in 105
plasma cells.2 c
DNA sequencing assay on BM
aspirate should use a validated assay. Baseline samples required for identification of the dominant clonotype; alternatively, a stored sample from a time point with detectable disease can be used to define baseline
status. Sample requirement is <1 million cells, higher numbers improve sensitivity. High sensitivity with NGS (≥10-5
); sample processing can be delayed, and both fresh and stored samples may be used.3,4 d
Criteria used
by Zamagni and colleagues and expert panel (IMPetUS). Baseline positive lesions were identified by presence of focal areas of increased uptake within bones, with or without any underlying lesion identified by CT
and present on at least two consecutive slices. Alternatively, an SUVmax = 2.5 within osteolytic CT areas>1 cm in size, or SUVmax = 1.5 within osteolytic CT areas = 1 cm in size were considered positive. Imaging should
be performed once MRD negativity is determined by MFC or NGS.5
ALL: acute lymphoblastic leukemia; ASCT: autologous stem cell transplant; BM: bone marrow; FCM: flow cytometry; HCT: hematopoietic cell transplant; IMPetUS: Italian Myeloma Criteria for PET Use; IMWG:
International Myeloma Working Group; MFC: multiparameter flow cytometry; MRD: minimal residual disease; NGF: next-generation flow; NGS: next-generation sequencing; NCCN: National Comprehensive
Cancer Network; SUV: standardized uptake value.
1. NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma. V.2.2020. https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Accessed February 4, 2020. 2. Paiva B et al. Blood.
2012;119:687-691. 3. Kumar S et al. Lancet Oncol. 2016;17:e328-346. 4. Anderson KC et al. Clin Cancer Res. 2017;23:3980-3993. 5. Zamagni E at al. Clin Cancer Res. 2015;21:4384-4390.
6. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm622004.htm. Accessed February 4, 2020.
Access the activity, “Changing Perspectives on Multiple Myeloma and
ASCT: Clinical Decision-Making, New Evidence, and Expanding Therapeutic
Options,” at PeerView.com/JHF40
MRD has been identified as an important prognostic factor in myeloma.
The NCCN recommends assessing for MRD as part of post-HCT follow-up.
The IMWG has provided a definition of treatment response in myeloma,
including for the achievement of MRD-negative disease; the latter requires a
complete response as defined below.
ClonoSEQ: in vitro NGS diagnostic assay; FDA-cleared for the detection and monitoring
of MRD in bone marrow samples from multiple myeloma and B-cell ALL patients6
Sustained
MRD negativity in the bone marrow
(NGS, NGF, or both) and by imaging, as
defined below, confirmed minimum of
1 year apart. Subsequent evaluations can be
used to further specify the duration of
negativity (eg, MRD negative at 5 years).a
Absence of clonal plasma cells by NGS on
bone marrow aspirate in which presence of
a clone is defined as less than two identical
sequencing reads obtained after DNA
sequencing of bone marrow aspirates using
a validated equivalent method with a
minimum sensitivity of 1 in 105
nucleated
cellsc
or higher.
Absence of phenotypically aberrant clonal
plasma cells by NGFb
on bone marrow
aspirates using the EuroFlow standard
operating procedure for MRD detection in
multiple myeloma (or validated equivalent
method) with a minimum sensitivity
of 1 in 105
nucleated cells or higher.
MRD negativity as defined by NGF or NGS
plus disappearance of every area of
increased tracer uptake found at baseline
or a preceding FDG PET/CT or decrease to
less mediastinal blood pool SUV or
decrease to less than that of surrounding
normal tissue.d
Sequencing
Flow
Imaging Plus
MRD
negative
T O O AC TC AT OC A