Introduction
Methods
Patients
Treatment
Efficacy assessment
Safety assessment
Statistical methods
Results
Patient characteristics
Arm A (plitidepsin plus DXM) (n = 171) | Arm B (DXM) (n = 84) | ||||
---|---|---|---|---|---|
n
| % |
n
| % | ||
Gender | Female | 74 | 43.3 | 49 | 58.3 |
Male | 97 | 56.7 | 35 | 41.7 | |
Age (years) | Median (range) | 64 (36–85) | 65 (42–85) | ||
ECOG PS at baseline | 0 | 68 | 39.8 | 31 | 36.9 |
1 | 74 | 43.3 | 42 | 50.0 | |
≥ 2 | 29a | 16.9 | 11 | 13.1 | |
MM type at diagnosis | Non-secretory | 6 | 3.5 | 1 | 1.2 |
Secretory | 165 | 96.5 | 83 | 98.8 | |
MM type at baselineb | Non-secretory | 17 | 10.1 | 2 | 2.4 |
Secretory | 151 | 89.9 | 80 | 97.6 | |
Durie-Salmon stage at diagnosis | I | 21 | 12.4 | 11 | 13.1 |
II | 48 | 28.1 | 21 | 25.0 | |
III | 101 | 59.1 | 51 | 60.7 | |
Cytogenetic risk group at baselinec | Standard risk | 47 | 27.5 | 22 | 26.2 |
High risk | 45 | 26.3 | 20 | 23.8 | |
Not available | 79 | 46.2 | 42 | 50.0 | |
Beta-2 microglobulin (mg/L) | Median (range) | 4.1 (0.0–27.3) | 4.2 (0.2–65.0) | ||
Hemoglobin (g/dL) | Median (range) | 10.4 (7.0–14.6) | 10.1 (7.4–14.6) | ||
Platelets (109/L) | Median (range) | 140 (11.0–517.0) | 154.0 (24.0–452.0) | ||
Neutrophils (109/L) | Median (range) | 2.2 (0.5–7.6) | 2.3 (0.5–10.3) | ||
CLCR (mL/min) | Median (range) | 72.9 (21.9–252.2) | 69.4 (23.0–137.0) | ||
% plasma cells | Median (range) | 40.0 (0.0–100.0) | 33.3 (0.0–100.0) | ||
Disease status | |||||
Relapsed and refractory to lenalidomide/thalidomide and bortezomib | 65 | 38.0 | 33 | 39.3 | |
Relapsed and refractory to lenalidomide/thalidomide but not to bortezomib | 39 | 22.8 | 24 | 28.6 | |
Relapsed and refractory to bortezomib but not to lenalidomide/thalidomide | 20 | 11.7 | 12 | 14.3 | |
Other than above | 47 | 27.5 | 15 | 17.9 | |
Disease status with respect to the last prior therapyd,e | Relapsed | 34 | 19.9 | 15 | 17.9 |
Total refractory | 126 | 73.7 | 62 | 73.8 | |
Refractory | 71 | 41.5 | 39 | 46.4 | |
Relapsed and refractory | 55 | 32.2 | 23 | 27.4 | |
Unknown | 11 | 6.4 | 7 | 8.3 | |
Prior stem cell transplantation | Number of SCT | ||||
0 | 56 | 32.7 | 29 | 34.5 | |
1 | 82 | 48.0 | 39 | 46.4 | |
≥ 2 | 33 | 19.3 | 16 | 19.0 | |
Type | |||||
Allogenic | 6 | 5.2 | 5 | 9.1 | |
Autologous | 115 | 100.0 | 54 | 98.2 |
Efficacy
Safety
Arm A (plitidepsin plus DXM) (n = 167) | Arm B (DXM) (n = 83)a | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
NCI-CTCAE grade | NCI-CTCAE grade | |||||||||||
All | 3 | 4 | All | 3 | 4 | |||||||
n
| % |
n
| % |
n
| % |
n
| % |
n
| % |
n
| % | |
Hematological abnormalities (regardless of relationship)b | ||||||||||||
Anemia | 157 | 98.1 | 48 | 30.0 | 2 | 1.3 | 77 | 97.5 | 26 | 32.9 | 2 | 2.5 |
Lymphopenia | 110 | 68.8 | 32 | 20.0 | 5 | 3.1 | 54 | 69.2 | 11 | 14.1 | 2 | 2.6 |
Thrombocytopenia | 95 | 59.4 | 21 | 13.1 | 14 | 8.8 | 53 | 67.1 | 9 | 11.4 | 13 | 16.5 |
Leukopenia | 84 | 52.5 | 14 | 8.8 | 2 | 1.3 | 37 | 46.8 | 2 | 2.5 | . | . |
Neutropenia | 76 | 47.5 | 22 | 13.8 | 3 | 1.9 | 33 | 42.3 | 3 | 3.8 | 1 | 1.3 |
Biochemical abnormalities (regardless of relationship)b | ||||||||||||
Increased ALT | 135 | 84.9 | 20 | 12.6 | 3 | 1.9 | 16 | 20.3 | . | . | . | . |
Increased creatinine | 132 | 82.5 | 2 | 1.3 | 1 | 0.6 | 70 | 88.6 | 2 | 2.5 | 1 | 1.3 |
Increased AST | 103 | 66.0 | 13 | 8.3 | 1 | 0.6 | 19 | 24.4 | . | . | . | . |
Increased CPK | 69 | 44.5 | 13 | 8.4 | 18 | 11.6 | 3 | 4.3 | . | . | . | . |
Increased ALP | 49 | 31.0 | 2 | 1.3 | 1 | 0.6 | 10 | 13.0 | . | . | . | . |
Increased bilirubin | 18 | 11.3 | 3 | 1.9 | . | . | 7 | 8.9 | . | . | . | . |
Adverse events (treatment-related or with unknown relationship) | ||||||||||||
Nausea | 62 | 37.1 | 6 | 3.6 | . | . | 9 | 10.8 | 1 | 1.2 | . | . |
Fatigue | 61 | 36.5 | 17 | 10.2 | 1 | 0.6 | 7 | 8.4 | 1 | 1.2 | . | . |
Myalgia | 24 | 14.4 | 7 | 4.2 | 2 | 1.2 | 2 | 2.4 | . | . | . | . |
Vomiting | 28 | 16.8 | 3 | 1.8 | . | . | 2 | 2.4 | 1 | 1.2 | . | . |
Diarrhea | 24 | 14.4 | 2 | 1.2 | . | . | 2 | 2.4 | . | . | . | . |
Peripheral edema | 20 | 12.0 | 2 | 1.2 | . | . | 2 | 2.4 | . | . | . | . |
Decreased appetite | 21 | 12.6 | 1 | 0.6 | . | . | 2 | 2.4 | . | . | . | . |