Smoldering multiple myeloma

Back to Top
Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
Note: due to its size/complexity, multiple myeloma has been split into sub-pages:
*Induction (transplant eligible and ineligible)
*First-line consolidation and maintenance
*Relapsed/refractory, including subsequent consolidation and maintenance 
*Smoldering multiple myeloma [this page]
Last updated on 2024-12-02:3 regimens on this page
5 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Multiple Myeloma.
=All lines of therapy=
==Daratumumab and hyaluronidase monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Dimopoulos et al. 2024 (AQUILA)	2017-12-10 to 2019-05-27	Phase 3 (E-esc)	Observation	Longer PFS (primary endpoint)PFS60: 63.1% vs 40.8%(HR 0.49, 95% CI 0.36-0.67)Seems to have longer OS (secondary endpoing)OS60: 93% vs 86.9%(HR 0.52, 95% CI 0.27-0.98)
====Targeted therapy====
*Daratumumab and hyaluronidase (Darzalex Faspro) as follows:
**Cycles 1 & 2: 1800 mg SC once per day on days 1, 8, 15, 22
**Cycles 3 to 6: 1800 mg SC once per day on days 1 & 15
**Cycles 7 to 39: 1800 mg SC once on day 1
28-day cycle for 39 cycles (3 years)
===References===
# AQUILA: Dimopoulos MA, Voorhees PM, Schjesvold F, Cohen YC, Hungria V, Sandhu I, Lindsay J, Baker RI, Suzuki K, Kosugi H, Levin MD, Beksac M, Stockerl-Goldstein K, Oriol A, Mikala G, Garate G, Theunissen K, Spicka I, Mylin AK, Bringhen S, Uttervall K, Pula B, Medvedova E, Cowan AJ, Moreau P, Mateos MV, Goldschmidt H, Ahmadi T, Sha L, Cortoos A, Katz EG, Rousseau E, Li L, Dennis RM, Carson R, Rajkumar SV; AQUILA Investigators. Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma. N Engl J Med. 2024 Dec 9. Epub ahead of print. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03301220
==Lenalidomide monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Lonial et al. 2019 (ECOG E3A06)	2011-2013 	Phase 3 (E-esc)	Observation	Longer PFS (primary endpoint)PFS36: 91% vs 66%(HR 0.28, 95% CI 0.12-0.62)
====Targeted therapy====
*Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
====Supportive therapy====
*Aspirin 325 mg PO once per day
28-day cycles
===References===
# ECOG E3A06: Lonial S, Jacobus S, Fonseca R, Weiss M, Kumar S, Orlowski RZ, Kaufman JL, Yacoub AM, Buadi FK, O'Brien T, Matous JV, Anderson DM, Emmons RV, Mahindra A, Wagner LI, Dhodapkar MV, Rajkumar SV. Randomized trial of lenalidomide versus observation in smoldering multiple myeloma. J Clin Oncol. 2020 Apr 10;38(11):1126-1137. Epub 2019 Oct 25. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01169337
==Lenalidomide & Dexamethasone (Rd)==
Rd: Revlimid (Lenalidomide) & low-dose dexamethasone
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Mateos et al. 2013 (QUIREDEX)	2007-2010 	Phase 3 (E-esc)	Observation	Longer TTP (primary endpoint)Median TTP: NYR vs 21 mo(HR 0.18, 95% CI 0.09-0.32)Longer OS (secondary endpoint)OS36: 94% vs 80%(HR 0.31, 95% CI 0.10-0.91)
Note: QUIREDEX did not require modern imaging modalities (such as MRI) to rule out active myeloma, and therefore it is probable that many patients on this study had active as opposed to smoldering multiple myeloma.
====Targeted therapy====
*Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4, 12 to 15
====Supportive therapy====
*Aspirin 100 mg PO once per day
28-day cycle for 9 cycles
====Subsequent treatment====
*Lenalidomide maintenance
===References===
# QUIREDEX: Mateos MV, Hernández MT, Giraldo P, de la Rubia J, de Arriba F, López Corral L, Rosiñol L, Paiva B, Palomera L, Bargay J, Oriol A, Prosper F, López J, Olavarría E, Quintana N, García JL, Bladé J, Lahuerta JJ, San Miguel JF. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med. 2013 Aug 1;369(5):438-47. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00480363
##Update: Mateos MV, Hernández MT, Giraldo P, de la Rubia J, de Arriba F, Corral LL, Rosiñol L, Paiva B, Palomera L, Bargay J, Oriol A, Prosper F, López J, Arguiñano JM, Quintana N, García JL, Bladé J, Lahuerta JJ, Miguel JS. Lenalidomide plus dexamethasone versus observation in patients with high-risk smouldering multiple myeloma (QuiRedex): long-term follow-up of a randomised, controlled, phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1127-1136. Epub 2016 Jul 9. link to original article EuroPMC
##Update: Mateos MV, Hernández MT, Salvador C, Rubia J, de Arriba F, López-Corral L, Rosiñol L, Paiva B, Palomera L, Bargay J, Oriol A, Prosper F, López J, Arguiñano JM, Bladé J, Lahuerta JJ, San-Miguel J. Lenalidomide-dexamethasone versus observation in high-risk smoldering myeloma after 12 years of median follow-up time: A randomized, open-label study. Eur J Cancer. 2022 Oct;174:243-250. Epub 2022 Sep 5. link to original article EuroPMC
#DETER-SMM: NCT03937635
#EFC15992: NCT03941860
#ITHACA: NCT04270409
==Thalidomide monotherapy==
===Regimen variant #1, 200 mg/d, indefinite therapy===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Barlogie et al. 2008 (UARK 98-036)	1998 to not reported	Phase 2 	 	
Witzig et al. 2012 (MC0289) 	2003-2008 	Phase 3 (E-esc)	Observation	Longer TTP (primary endpoint)Median TTP: 2.4 vs 1.2 y(HR 0.49, 95% CI 0.26-0.91)
Note: Zoledronic acid was received in both the control and experimental arms.
====Targeted therapy====
*Thalidomide (Thalomid) 200 mg PO once per day
====Supportive therapy====
*Zoledronic acid (Zometa) 4 mg IV once every three months
Continued indefinitely
===Regimen variant #2, 200 -> 600 mg/d, indefinite therapy===
Study 	Dates of enrollment	Evidence
Weber et al. 2003	1999-2001 	Phase 1/2
Note: The median maximal tolerated dose in this study for patients with smoldering myeloma was 400 mg PO once per day
====Targeted therapy====
*Thalidomide (Thalomid) as follows: 
**Cycle 1: 200 mg PO once per day on days 1 to 7, then 300 mg PO once per day on days 8 to 14, then 400 mg PO once per day on days 15 to 21, then 500 mg PO once per day on days 22 to 28
**Cycle 2 onwards: 600 mg PO once per day on days 1 to 28
28-day cycles
===Regimen variant #3, 200 -> 800 mg/d, indefinite therapy===
Study 	Dates of enrollment	Evidence
Rajkumar et al. 2001	Not reported 	Phase 2
====Targeted therapy====
*Thalidomide (Thalomid) as follows: 
**Cycle 1: 200 mg PO once per day on days 1 to 14, then 400 mg PO once per day on days 15 to 28
**Cycle 2: 600 mg PO once per day on days 1 to 14, then 800 mg PO once per day on days 15 to 28
**Cycle 3 onwards: 800 mg PO once per day on days 1 to 28
28-day cycles
===References===
# Rajkumar SV, Dispenzieri A, Fonseca R, Lacy MQ, Geyer S, Lust JA, Kyle RA, Greipp PR, Gertz MA, Witzig TE. Thalidomide for previously untreated indolent or smoldering multiple myeloma. Leukemia. 2001 Aug;15(8):1274-6. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# Weber D, Rankin K, Gavino M, Delasalle K, Alexanian R. Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol. 2003 Jan 1;21(1):16-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# UARK 98-036: Barlogie B, van Rhee F, Shaughnessy JD Jr, Epstein J, Yaccoby S, Pineda-Roman M, Hollmig K, Alsayed Y, Hoering A, Szymonifka J, Anaissie E, Petty N, Kumar NS, Srivastava G, Jenkins B, Crowley J, Zeldis JB. Seven-year median time to progression with thalidomide for smoldering myeloma: partial response identifies subset requiring earlier salvage therapy for symptomatic disease. Blood. 2008 Oct 15;112(8):3122-5. Epub 2008 Jul 31. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00083382
# MC0289: Witzig TE, Laumann KM, Lacy MQ, Hayman SR, Dispenzieri A, Kumar S, Reeder CB, Roy V, Lust JA, Gertz MA, Greipp PR, Hassoun H, Mandrekar SJ, Rajkumar SV. A phase III randomized trial of thalidomide plus zoledronic acid versus zoledronic acid alone in patients with asymptomatic multiple myeloma. Leukemia. 2013 Jan;27(1):220-5. Epub 2012 Aug 20. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00432458
##Update: Abdallah N, Witzig TE, Kumar SK, Lacy MQ, Hayman SR, Dispenzieri A, Roy V, Gertz MA, Bergsagel PL, Rajkumar SV. Phase III randomized trial of Thal+ZLD versus ZLD in patients with asymptomatic multiple myeloma - updated results after 18-year follow-up. Leukemia. 2024 May;38(5):1169-1171. Epub 2024 Feb 28. link to original article EuroPMC
Category:Smoldering multiple myeloma regimens
Category:Disease-specific pages
Category:Plasma cell dyscrasias