Selected clinical studies of strategies to prevent progression of SMM, MGUS, and early-stage multiple myeloma
| Reference . | Study design . | Intervention . | No. of patients . | Outcome/comment . |
|---|---|---|---|---|
| Hjorth 199348 | Randomized controlled trial | Initial vs deferred MP therapy | 50 SMM and IMM (25/25) | Similar response rate, response duration, and survival |
| Rajkumar 200156 | Single-arm pilot study | Thalidomide | 16 SMM and IMM | MR or better in 11/16; microvessel density did not predict response |
| Musto 200850 | Open-label, randomized controlled trial | Zoledronate | 163 SMM (81/82) | Zoledronate for 1 y decreased risk of skeletal-related disease, but TTP was similar (P = .83) |
| Barlogie 200849 | Single-arm phase 2 trial | Thalidomide/pamidronate | 76 SMM | Median TTP 7 y; PR identifies subset requiring earlier salvage therapy for symptomatic disease |
| Lust 200957 | Single-arm phase 2 trial | Anakinra (IL-1 receptor antagonist) | 47 SMM and IMM (25 received anakinra and DEX) | Median PFS was 37.5 mo MR (n = 3), PR (n = 5); 8 patients stable on drug for 4 y |
| Golombick 200958 | Single-blind, randomized, crossover pilot study | Curcumin vs placebo | 26 MGUS | 5 of 10 patients with M-protein > 2 g/dL had decreased M-protein (12%-30% reduction) |
| Kalaycio 2004-ongoing59 | Double-blind, randomized controlled trial | Celoxicib vs placebo | 36 MGUS and SMM | Aim: to test whether celoxicib reduces the M-protein concentration |
| Mateos 2007-ongoing60 | Open-label randomized controlled trial | Lenalidomide + DEX vs observation | 120 “high-risk” SMM | Aim: to evaluate whether lenalidomide + DEX extends TTP |
| Ballester 2009-ongoing61 | Unblinded, nonrandomized trial | Omega-3 fatty acids | 48 MGUS, SMM, or CLL* | Aim: to assess whether omega-3 fatty acids reduce activated NF-κB levels in peripheral blood lymphocytes |
| Zonder 2009-ongoing62 | Single-arm pilot study | Green tea extract | 17 MGUS or SMM* | Aim: to test whether green tea extract reduces the M-protein concentration |
| Lonial 2010-ongoing63 | Open-label randomized controlled trial | Lenalidomide vs observation | 370 “high-risk” SMM* | Aim: to evaluate whether lenalidomide extends TTP |
| Landgren 2010-ongoing64 | Single-arm phase 2 trial | Anti-KIR monoclonal antibody | 21 SMM | Aim: to evaluate whether anti-KIR reduces the M-protein concentration > 50% from baseline |
| Reference . | Study design . | Intervention . | No. of patients . | Outcome/comment . |
|---|---|---|---|---|
| Hjorth 199348 | Randomized controlled trial | Initial vs deferred MP therapy | 50 SMM and IMM (25/25) | Similar response rate, response duration, and survival |
| Rajkumar 200156 | Single-arm pilot study | Thalidomide | 16 SMM and IMM | MR or better in 11/16; microvessel density did not predict response |
| Musto 200850 | Open-label, randomized controlled trial | Zoledronate | 163 SMM (81/82) | Zoledronate for 1 y decreased risk of skeletal-related disease, but TTP was similar (P = .83) |
| Barlogie 200849 | Single-arm phase 2 trial | Thalidomide/pamidronate | 76 SMM | Median TTP 7 y; PR identifies subset requiring earlier salvage therapy for symptomatic disease |
| Lust 200957 | Single-arm phase 2 trial | Anakinra (IL-1 receptor antagonist) | 47 SMM and IMM (25 received anakinra and DEX) | Median PFS was 37.5 mo MR (n = 3), PR (n = 5); 8 patients stable on drug for 4 y |
| Golombick 200958 | Single-blind, randomized, crossover pilot study | Curcumin vs placebo | 26 MGUS | 5 of 10 patients with M-protein > 2 g/dL had decreased M-protein (12%-30% reduction) |
| Kalaycio 2004-ongoing59 | Double-blind, randomized controlled trial | Celoxicib vs placebo | 36 MGUS and SMM | Aim: to test whether celoxicib reduces the M-protein concentration |
| Mateos 2007-ongoing60 | Open-label randomized controlled trial | Lenalidomide + DEX vs observation | 120 “high-risk” SMM | Aim: to evaluate whether lenalidomide + DEX extends TTP |
| Ballester 2009-ongoing61 | Unblinded, nonrandomized trial | Omega-3 fatty acids | 48 MGUS, SMM, or CLL* | Aim: to assess whether omega-3 fatty acids reduce activated NF-κB levels in peripheral blood lymphocytes |
| Zonder 2009-ongoing62 | Single-arm pilot study | Green tea extract | 17 MGUS or SMM* | Aim: to test whether green tea extract reduces the M-protein concentration |
| Lonial 2010-ongoing63 | Open-label randomized controlled trial | Lenalidomide vs observation | 370 “high-risk” SMM* | Aim: to evaluate whether lenalidomide extends TTP |
| Landgren 2010-ongoing64 | Single-arm phase 2 trial | Anti-KIR monoclonal antibody | 21 SMM | Aim: to evaluate whether anti-KIR reduces the M-protein concentration > 50% from baseline |
Adapted from Waxman et al.54
SMM indicates smoldering multiple myeloma; MGUS, monoclonal gammopathy of undetermined significance; MP, melphalan/prednisone; IMM indolent multiple myeloma (asymptomatic but with evidence of end-organ damage); MR, minor response (25%-50% decrease in M-protein); TTP, time to progression; DEX, dexamethasone; PFS, progression-free survival; and PR, partial response (≥ 50% decrease in M-protein).
Estimated enrollment