Robert Z. Orlowski, MD, PhD, prepared useful practice aids pertaining to multiple myeloma management for this CME/CNE activity titled "Driving Change in Multiple Myeloma: Updates on Novel Agent Classes and Next-Generation Therapeutics." For the full presentation, monograph, complete CME/CNE information, and to apply for credit, please visit us at http://bit.ly/2SPKaZZ. CME/CNE credit will be available until August 7, 2020.

1. Access the activity, “Driving Change in Multiple Myeloma: Updates on Novel
Agent Classes and Next-Generation Therapeutics,” at PeerView.com/TXD40.
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.3.2019. https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Accessed July 1, 2019.
Please consult NCCN guidelines for additional information regarding the regimens listed here, including summary of indications for use.
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 1
Bortezomib/doxorubicin/
dexamethasone
Category 2B
Ixazomib/lenalidomidea
/
dexamethasone
Category 2A
Carfilzomibc,d
/lenalidomidea
/
dexamethasone
Category 1
• Bortezomib/dexamethasonee
• Bortezomib/thalidomide/
dexamethasone
• Lenalidomidea
/dexamethasonee
Category 2A
• Dexamethasone/thalidomide/
cisplatin/doxorubicin/
cyclophosphamide/etoposide/
bortezomib (VTD-PACE)
• Cyclophosphamide/
lenalidomidea
/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

2. Access the activity, “Driving Change in Multiple Myeloma: Updates on Novel
Agent Classes and Next-Generation Therapeutics,” at PeerView.com/TXD40.
The Multiple Myeloma Treatment Pyramid:
Recommendations for Non–ASCT-Eligible
Patients1
PRACTICE AID
a
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. b
Continuously until progression.
Benboubker L et al. N Engl J Med. 2014;371:906-917. c
Preferred initial treatment in patients with acute renal insufficiency. Consider switching to bortezomib/lenalidomide/dexamethasone after renal
function improves. d
May interfere with serological testing and cause false-positive indirect Coombs test. e
Can potentially cause cardiac and pulmonary toxicity, especially in elderly patients.
ASCT: autologous stem cell transplant.
1. NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma. V.3.2019. https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Accessed July 1, 2019. 2. https://www.fda.gov/drugs/
resources-information-approved-drugs/fda-approves-daratumumab-multiple-myeloma-ineligible-autologous-stem-cell-transplant. Accessed July 5, 2019.
Please consult NCCN guidelines for additional information regarding the regimens listed here, including summary of indications for use.
Other
recommended
regimens
Preferred
regimens
Useful in certain
circumstances
Newly Diagnosed Transplant-Ineligible Patients
Category 2A
Bortezomib/cyclophosphamide/
dexamethasonec
Category 1
Category 2A
• Bortezomib/dexamethasonea
• Cyclophosphamide/
lenalidomide/dexamethasone
Category 2A
• Carfilzomibe
/lenalidomide/
dexamethasone
• Carflizomibe
/cyclophosphamide/
dexamethasone
• Ixazomib/lenalidomide/
dexamethasone
• Bortezomib/lenalidomide/
dexamethasone
• Lenolidomide/low-dose
dexamethasonea,b
• Daratumumabd
/bortezomib/
melphalan/prednisone
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
Daratumumab/lenalidomide/
dexamethasone recently
approved for use in
transplant-ineligible patients2

3. Access the activity, “Driving Change in Multiple Myeloma: Updates on Novel
Agent Classes and Next-Generation Therapeutics,” at PeerView.com/TXD40.
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.3.2019. https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Accessed July 1, 2019. 2. Richardson PG et al. 2019
American Society of Clinical Oncology Annual Meeting (ASCO 2019). Abstract 8004. 3. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-selinexor-
multiple-myeloma. Accessed July 1, 2019.
Please consult NCCN guidelines for additional information regarding the regimens listed here, including summary of indications for use.
PRACTICE AID
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
/pomalidomide/
dexamethasone
• Elotuzumab/bortezomib/
dexamethasone
• Elotuzumab/pomalidomide/
dexamethasone
• Ixazomib/dexamethasoneb
• Ixazomib/pomalidomide/
dexamethasone
• Panobinostat/carfilzomiba,b
• Panobinostat/lenalidomide/
dexamethasone
• Pomalidomide/cyclophosphamide/
dexamethasone
• Pomalidomide/bortezomib/
dexamethasone
• Pomalidomide/carfilzomiba
/
dexamethasone
Category 2A
• Bendamustine
• High-dose cyclophosphamide
Generally reserved for aggressive disease
• Dexamethasone/
cyclophosphamide/etoposide/
cisplatin (DCEP)
• Dexamethasone/thalidomide/
cisplatin/doxorubicin/
cyclophosphamide/etoposide
(DT-PACE) ± bortezomib (VTD-PACE)
• In phase 3 ICARIA-MM trial, the addition of
the next-generation anti-CD38 antibody
isatuximab to pomalidomide and
dexamethasone substantially improved PFS
vs doublet therapy in patients with R/R MM2
• 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 a CD38 antibody)3
Category 2A
• Bortezomib/lenalidomide/dexamethasone
• Carfilzomib (weekly)a
/dexamethasoneb
Category 1
• Bortezomib/liposomal
doxorubicin/dexamethasone
• Bortezomib/dexamethasoneb
• Lenalidomide/
dexamethasoneb,e
• Panobinostat/bortezomib/
dexamethasone
• Pomalidomide/
dexamethasoneb,e
Category 1
• Carfilzomib (2 x wk)a
/
dexamethasoneb
• Carfilzomiba
/lenalidomide/
dexamethasonec
• Daratumumabd
/bortezomib/
dexamethasone
• Daratumumabd
/lenalidomide/
dexamethasone
• Elotuzumab/lenalidomide/
dexamethasonec
• Ixazomib/lenalidomide/
dexamethasonec
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
Recent updates in R/R MM