Selected phase 2 and 3 clinical trials for treatment of SMM with reported outcomes
| Trial . | Phase . | SMM risk inclusion criteria . | Intervention . | Control arm . | Results . | Toxicity . |
|---|---|---|---|---|---|---|
| QuiRedex29,30 | 3 | Both BMPC ≥10% and IgG ≥3 g/dL (or IgA ≥2 g/dL or urine M-protein >1 g/24 h) OR only 1 of the criteria above plus ≥95% aberrant PC and immunoparesis | Lenalidomide (25 mg) and dexamethasone for 9 cycles followed by lenalidomide (10 mg) maintenance for 2 years (n = 57) | Observation (n = 62) | Median TTP (progression defined as end-organ damage) not reached vs 23 months (HR, 0.24), median OS not reached (HR, 0.43) | 16 cases of grade 3 toxicities in intervention arm, 1 treatment-associated death. Second cancers more common in treatment arm (10% vs 2%). |
| ECOG E3A0631 | 3 | BMPC ≥10%-60% and abnormal FLC ratio (<0.26 or >1.65) | Lenalidomide (25 mg per day on days 1-21 every 28-day cycle) until progression (n = 90) | Observation (n = 92) | 3-year PFS (progression defined as biochemical or end-organ damage) 91% vs 66% (HR, 0.28) | Grade 3 or 4 toxicity in 36 (41%) patients; 18 patients discontinued treatment because of toxicities. One treatment-associated death; 3-year cumulative incidence of second cancers 5.2% vs 3.5%. |
| CENTAURUS37 | 2 | BMPC 10%-60% and 1 of the following: IgG ≥3 g/dL, IgA ≥2 g/dL, urine M-protein >500 mg/24 h, FLC ratio <0.126 or >8 (and serum M-protein <3 g/dL but ≥1 g/d) | Daratumumab monotherapy in 3 different regimens: intense (n = 41), intermediate (n = 41), and short (n = 41) | No | ORR of 56%, 53.7%, and 37.5% in the intensive, intermediate, and short arms, respectively | Grade 3 or 4 toxicities in 44% of patients in the intense arm, 26.8% in the intermediate arm, and 15.0% in the short arm |
| GEM-CESAR35 | 2 | Both ≥10% BMPC and M-protein ≥3 g/dL OR 1 of the criteria above plus ≥95% aberrant PC and immunoparesis | Carfilzomib, lenalidomide, and dexamethasone for 6 cycles (induction), HDT and ASCT, carfilzomib, lenalidomide, and dexamethasone for 2 cycles (consolidation) and lenalidomide and dexamethasone maintenance for 2 years (n = 90) | No | ORR of 100%. MRD negativity of 67% at 1 year posttreatment | 46 cases of grade 3 or 4 toxicities have been reported |
| Kazandjian 202134 | 2 | High risk per Mayo Clinic 2018 model or PETHEMA OR both BMPC ≥10% and 1 of the following: M-protein ≥3 g/dL, IgA isotype, immunoparesis, FLC ratio >8, progressive increase in M-protein, BMPC 50%-60%, t(4;14) or del(17p) or 1q gain, increased circulating PC, MRI with diffuse abnormalities or 1 focal lesion, PET/CT with focal lesion with increased uptake | Carfilzomib, lenalidomide, and dexamethasone for 8 cycles followed by 24 cycles of lenalidomide (n = 54) | No | ORR of 100%. MRD negativity was 70% with a median duration of 5.5 years. | Nonhematologic grade 3 toxicities in 21 patients (38.9%) |
| Mailankody 201938 | 2 | Mayo Clinic 2018 model or Spanish PETHEMA criteria | Isatuximab until disease progression or unacceptable toxicity (n = 61) | No | ORR of 62.5% | 5 cases of grade 3 toxicities |
| Trial . | Phase . | SMM risk inclusion criteria . | Intervention . | Control arm . | Results . | Toxicity . |
|---|---|---|---|---|---|---|
| QuiRedex29,30 | 3 | Both BMPC ≥10% and IgG ≥3 g/dL (or IgA ≥2 g/dL or urine M-protein >1 g/24 h) OR only 1 of the criteria above plus ≥95% aberrant PC and immunoparesis | Lenalidomide (25 mg) and dexamethasone for 9 cycles followed by lenalidomide (10 mg) maintenance for 2 years (n = 57) | Observation (n = 62) | Median TTP (progression defined as end-organ damage) not reached vs 23 months (HR, 0.24), median OS not reached (HR, 0.43) | 16 cases of grade 3 toxicities in intervention arm, 1 treatment-associated death. Second cancers more common in treatment arm (10% vs 2%). |
| ECOG E3A0631 | 3 | BMPC ≥10%-60% and abnormal FLC ratio (<0.26 or >1.65) | Lenalidomide (25 mg per day on days 1-21 every 28-day cycle) until progression (n = 90) | Observation (n = 92) | 3-year PFS (progression defined as biochemical or end-organ damage) 91% vs 66% (HR, 0.28) | Grade 3 or 4 toxicity in 36 (41%) patients; 18 patients discontinued treatment because of toxicities. One treatment-associated death; 3-year cumulative incidence of second cancers 5.2% vs 3.5%. |
| CENTAURUS37 | 2 | BMPC 10%-60% and 1 of the following: IgG ≥3 g/dL, IgA ≥2 g/dL, urine M-protein >500 mg/24 h, FLC ratio <0.126 or >8 (and serum M-protein <3 g/dL but ≥1 g/d) | Daratumumab monotherapy in 3 different regimens: intense (n = 41), intermediate (n = 41), and short (n = 41) | No | ORR of 56%, 53.7%, and 37.5% in the intensive, intermediate, and short arms, respectively | Grade 3 or 4 toxicities in 44% of patients in the intense arm, 26.8% in the intermediate arm, and 15.0% in the short arm |
| GEM-CESAR35 | 2 | Both ≥10% BMPC and M-protein ≥3 g/dL OR 1 of the criteria above plus ≥95% aberrant PC and immunoparesis | Carfilzomib, lenalidomide, and dexamethasone for 6 cycles (induction), HDT and ASCT, carfilzomib, lenalidomide, and dexamethasone for 2 cycles (consolidation) and lenalidomide and dexamethasone maintenance for 2 years (n = 90) | No | ORR of 100%. MRD negativity of 67% at 1 year posttreatment | 46 cases of grade 3 or 4 toxicities have been reported |
| Kazandjian 202134 | 2 | High risk per Mayo Clinic 2018 model or PETHEMA OR both BMPC ≥10% and 1 of the following: M-protein ≥3 g/dL, IgA isotype, immunoparesis, FLC ratio >8, progressive increase in M-protein, BMPC 50%-60%, t(4;14) or del(17p) or 1q gain, increased circulating PC, MRI with diffuse abnormalities or 1 focal lesion, PET/CT with focal lesion with increased uptake | Carfilzomib, lenalidomide, and dexamethasone for 8 cycles followed by 24 cycles of lenalidomide (n = 54) | No | ORR of 100%. MRD negativity was 70% with a median duration of 5.5 years. | Nonhematologic grade 3 toxicities in 21 patients (38.9%) |
| Mailankody 201938 | 2 | Mayo Clinic 2018 model or Spanish PETHEMA criteria | Isatuximab until disease progression or unacceptable toxicity (n = 61) | No | ORR of 62.5% | 5 cases of grade 3 toxicities |
ASCT, autologous stem cell transplantation; HDT, high-dose chemotherapy; HR, hazard ratio; ORR, overall response rate; OS, overall survival; PC, plasma cells; PET/CT, positron emission tomography/computed tomography; PFS, progression-free survival; TTP, time to progression.