Table 1.
Summary of selected phase 2 and 3 studies within reported outcome data within the past decade
| Trial name/date | Study design | Criteria for defining SMM patient inclusion | Intervention (I) and control (C) arms | Median follow-up | Key outcomes |
|---|---|---|---|---|---|
| QUIREDEX Mateos et al (2013, updated 2016)39,40 | Phase 3 Randomized, open label |
SMM (diagnosed <5 years) and either: • BM PC ≥10% and M-protein (IgG ≥3 g/dL, IgA ≥2 g/dL, Bence-Jones proteinuria >1 g/24 h) • BM PC ≥10% or M-protein (defined as above), with ≥95% aberrant PC and immunoparesis (≥1 uninvolved immunoglobulin >25% below LLN) |
• I: Lenalidomide and dexamethasone (n = 57)—Lenalidomide 25 mg × 21/28 days for 9 cycles, then 10 mg × 21/28 days for a 2-year total duration. Dexamethasonase 20mg days 1-4 and days 12–15 of first 9 cycles and days 1-4 at biochemical progression. • C: Observation (n = 62) |
75 months* | Primary outcome—TTP (progression defined as end-organ damage) • Median TTP (I vs C): NR vs 23 months (HR, 0.24; 95% CI, 0.14-0.41) Secondary outcome—OS • Median OS (I vs C): NR in both groups (HR, 0.43; 95% CI, 0.21-0.92) |
| ECOG-ACRIN E3A06 Lonial et al (2019)10 |
Phase 2/3 Randomized, open label |
SMM (diagnosed <5 years) with ≥10% PCs and abnormal sFLC ratio (<0.26 or >1.65) | • I: Lenalidomide (n = 90)—25 mg (days 1-21 of 28 days), until progression or toxicity • C: Observation (n = 92) |
35 months | Primary outcome—PFS (progression defined as biochemical progression in addition to end-organ damage): • 3-year PFS (I vs C)—91% vs 66%, (HR, 0.28; 95% CI, 0.12-0.65) Additional outcomes (I vs C): • PFS in high-risk SMM subgroup (n = 56)—HR, 0.09 (95% CI, 0.02-0.44) • OS—HR, 0.46 (95% CI, 0.08-2.53) |
| CENTAURUS Landgren et al (2020)41 | Phase 2 Randomized, open label |
SMM (diagnosed <5 years) with absence of SLiM or CRAB criteria and 1 of: • Serum M-protein ≥ 3 g/dL • iFLC/uFLC >8 if serum M-protein 1-3 g/dL • Urine M-protein >500 mg/24 h • Serum iFLC ≥100 mg/dL (if iFLC/uFLC between 8 and 99) |
3 arms based on daratumumab 16-mg/kg IV dosing schedule: • Intense (n = 41)— Q1W × 8, Q2W × 8, Q4W × 8, Q8W × 8 • Intermediate (n = 41)—Q1W × 8, Q8W × 19 • Short (n = 41)—Q1W × 8 |
25.8 months (prespecified primary analysis) | Co-Primary endpoint—≥ Complete response rate: • Intense arm—4.9% • Intermediate arm—9.8% • Short arm—0% Co-Primary endpoint—Progression† (progression defined as biochemical or end-organ damage) or death rate per patient year: • Intense arm—4.9% • Intermediate arm—9.8% • Short arm—0% |
*
Median follow-up for surviving patients.40
†
Progression was defined based on the IMWG 2014 diagnostic criteria for MM, as well as the IMWG FLC progression criteria (a ≥25% increase from nadir in the difference between involved and uninvolved FLC with absolute increase >10 mg/dL).
C, control arm; CRAB, C-hyperCalcemia, R-Renal impairment, A-Anemia, B-Bone lesions related to multiple myeloma; iFLC, involved FLC; I, intervention arm; IV, intravenous; LLN, lower limit of normal; NR, not reached; sFLCr, serum FLC ratio; uFLC, uninvolved FLC.