Smoldering multiple myeloma - null regimens

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The purpose of this page is to provide references to "null therapy" such as placebo and observation. These references provide further insight into the historical development of the treatment landscape. See the main SMM page for regimens that include active anticancer treatment.
=All lines of therapy=
==Observation==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Hjorth et al. 1993 	1983-1988 	Phase 3 (C)	MP 	Did not meet endpoint of OS
Riccardi et al. 2000 (MM87/MM90)	1987-1993 	Phase 3 (C)	MP 	Did not meet endpoint of OS
Witzig et al 2012 (MC0289) 	2003-2008 	Phase 3 (C)	Thalidomide 	Shorter TTPMedian TTP: 1.2 vs 2.4 years(HR 2.04, 95% CI 1.10-3.85)
Mateos et al. 2013 (QUIREDEX) 	2007-2010 	Phase 3 (C)	Rd 	Shorter OS
Lonial et al. 2019 (ECOG E3A06) 	2011-2013 	Phase 3 (C)	Lenalidomide 	Shorter PFSPFS36: 66% vs 91%(HR 3.57, 95% CI 1.61-8.33)
Dimopoulos et al. 2024 (AQUILA) 	2017-12-10 to 2019-05-27	Phase 3 (C)	SC daratumumab	Shorter PFSSeems to have shorter OS
No myeloma-directed treatment.
===References===
# Hjorth M, Hellquist L, Holmberg E, Magnusson B, Rödjer S, Westin J; Myeloma Group of Western Sweden. Initial versus deferred melphalan-prednisone therapy for asymptomatic multiple myeloma stage I--a randomized study. Eur J Haematol. 1993 Feb;50(2):95-102. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# MM87/MM90: Riccardi A, Mora O, Tinelli C, Valentini D, Brugnatelli S, Spanedda R, De Paoli A, Barbarano L, Di Stasi M, Giordano M, Delfini C, Nicoletti G, Bergonzi C, Rinaldi E, Piccinini L, Ascari E; Cooperative Group of Study and Treatment of Multiple Myeloma. Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study. Br J Cancer. 2000 Apr;82(7):1254-60. link to original article dosing details in abstract have been reviewed by our editors link to PMC article EuroPMC
# 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
# 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
# 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
# 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 EuroPMC NCT03301220
Category:Smoldering multiple myeloma regimens
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Category:Plasma cell dyscrasias
Category:Null regimens