Table 1.
Selected Clinical Trials for Treatment of SMM
| Reference | Year of Publication | NCT No. | Trial Starting Year and Status | Study Design | Phase | Intervention | No. of Patients and Disease | Outcome/Comment | TTP (months) | ORR (%) |
|---|---|---|---|---|---|---|---|---|---|---|
| Alkylating agents | ||||||||||
| Alexanian et al41 | 1988 | Retrospective | Vincristine-doxorubicin-dexamethasone or melphalan-prednisone | 23 SMM; 10 IMM | Median OS: 105 months; deferral of treatment did not impact likelihood of remission or survival | 19 | 64 | |||
| Hjorth et al46 | 1993 | Randomized trial | Melphalan-prednisone; initial v deferred | 25 SMM and IMM | Median OS: 52 months; no significant difference in ORR or OS | 21 | 52-55 | |||
| Bisphosphonates only | ||||||||||
| Musto et al49 | 2008 | Randomized trial | III | Zoledronate v observation | 163 SMM | 1-year zoledronate decreased skeletal events; no significant difference in TTP or PFS | 67 | NA | ||
| Small molecules | ||||||||||
| Rajkumar et al50 | 2001 | Pilot single arm | Thalidomide | 16 SMM and IMM | MR or better: 69%; PR or better: 47.5% | NA | 69 | |||
| Barlogie et al43 | 2008 | Single arm | II | Thalidomide- pamidronate | 76 SMM | 4-year OS: 91%; high rates of dose reduction (86%) and discontinuation (50%) | 84 | 63 | ||
| Witzig et al51 | 2013 | Randomized trial | III | Thalidomide-zoledronate v zoledronate | 68 SMM | Median TTP: 2.4 (thalidomide and zoledronate) v 1.2 years (zoledronate only) (P = .02) | 29 | NR at 71 months | ||
| Mateos et al34 | 2013 | Randomized trial | III | Lenalidomide-dexamethasone v observation | 119 high-risk SMM | 3-year OS: 94% (treatment) v 80% (observation) (P = .03); high rate of discontinuation in patients given maintenance lenalidomide (30%) | NR at 40 months | 79-90 | ||
| NCT01169337 | 2010, ongoing | Randomized trial | III | Lenalidomide v observation | 370* high-risk SMM | End points: ORR, PFS, OS | — | — | ||
| NCT01572480 | 2012, ongoing | Single arm | II | Carfilzomib-lenalidomide-dexamethasone | 30 high-risk SMM | End points: ORR, PFS | — | — | ||
| NCT00983346 | 2009, ongoing | Pilot, single arm | Bortezomib | 20* SMM | End point: bone anabolic effect | — | — | |||
| Monoclonal antibodies or receptor antagonists | ||||||||||
| Lust et al52 | 2009 | Single arm | II | Anakinra | 47 SMM and IMM | Anakinra: IL-1 receptor antagonist; median PFS: 37.5 months; MR (n = 3), PR (n = 5) | 38† | NA | ||
| Korde et al52a | 2014 | Single arm | II | IPH2101 | 9* SMM | IPH2101: antiKIR Ab; MR (n = 1), stable disease (n = 6), progression (n = 2) | NA | 11 | ||
| NCT01222286 | 2010, completed | Randomized trial | II | IPH2101 | 30* SMM | IPH2101: anti-KIR Ab; results not published to date; end point: ORR | — | — | ||
| NCT01302886 | 2011, completed | Single arm | II | BHQ880 | 58* high-risk SMM | BHQ880: anti-DKK1 neutralizing Ab; results not published to date; end point: ORR | — | — | ||
| NCT01484275 | 2011, ongoing | Randomized trial | II | Siltuximab v placebo | 100* high-risk SMM | Siltuximab: anti-IL-6 mAb; end point: 1-year PFS | — | — | ||
| NCT01441973 | 2012, ongoing | Single arm | II | Elotuzumab | 58* high-risk SMM | Elotuzumab: anti-CS1 IgG1 mAb; end point: ORR | — | — | ||
| NCT01838369 | 2013, ongoing | Single arm | II | BI-505 | 10* SMM | BI-505: anti-intercellular adhesion molecule-1 mAb; end point: ORR | — | — |
Abbreviations: Ab, antibody; IgG1, immunoglobulin G1; IL-1, interleukin-1; IMM, indolent multiple myeloma; mAb, monoclonal antibody; MR, minor response (25%-50% decrease in M-protein); NA, not assessed; NR, not reached; ORR, overall response rate, including minor response; OS, overall survival; PFS, progression-free survival; PR, partial response (≥ 50% decrease in M-protein); SMM, smoldering multiple myeloma; TTP, time to progression.
*
Estimated number of enrolled participants.
†
Value for median PFS. TTP was not reported.