Table 1.
Baseline characteristics
| Characteristic | Part A (n = 63) |
Part B phase 1 (n = 14) |
Part B phase 2 (n = 36) |
|||
|---|---|---|---|---|---|---|
| Median age, y (range) | 69 (38-80) | 70 (47-79) | 70 (46-80) | |||
| <65, n (%) | 20 (31.7) | 5 (35.7) | 10 (27.8) | |||
| 65 to <75, n (%) | 30 (47.6) | 6 (42.9) | 15 (41.7) | |||
| ≥75, n (%) | 13 (20.6) | 3 (21.4) | 11 (30.6) | |||
| Sex, n (%) | ||||||
| Female | 24 (38.1) | 4 (28.6) | 17 (47.2) | |||
| Male | 39 (61.9) | 10 (71.4) | 19 (52.8) | |||
| WHO performance score, n (%) | ||||||
| 0 | 29 (46.0) | 8 (57.1) | 15 (41.7) | |||
| 1 | 25 (39.7) | 5 (35.7) | 16 (44.4) | |||
| 2 | 7 (11.1) | 1 (7.1) | 5 (13.9) | |||
| Unknown | 2 (3.2) | 0 | 0 | |||
| Extramedullary plasmacytomas, n (%) | ||||||
| No | 53 (84.1) | 12 (85.7) | 32 (88.9) | |||
| Yes | 8 (12.7) | 2 (14.3) | 3 (8.3) | |||
| Type of monoclonal heavy chain, n (%) | ||||||
| IgG | 36 (57.1) | 4 (28.6) | 26 (72.2) | |||
| IgA | 7 (11.1) | 1 (7.1) | 5 (13.9) | |||
| Light chain only | 13 (20.6) | 6 (42.9) | 3 (8.3) | |||
| Bence-Jones | 7 (11.1) | 3 (21.4) | 2 (5.6) | |||
| Type of light chain, n (%) | ||||||
| Kappa | 40 (63.5) | 2 (14.3) | 29 (80.6) | |||
| Lambda | 23 (36.5) | 12 (85.7) | 7 (19.4) | |||
| Time since start first treatment, median years (range) | 6.8 (1.5-16.0) | 7.1 (2.5-16.0) | 5.5 (1.9-14.8) | |||
| Prior lines of treatment, median (range) | 4 (2-11) | 8 (4-11) | 5 (3-12) | |||
| >3 prior lines, n (%) | 41 (65.1) | 14 (100) | 32 (88.9) | |||
| Autologous SCT, n (%) | 38 (60.3) | 10 (71.4) | 18 (50.0) | |||
| Allogeneic SCT, n (%) | 8 (12.7) | 2 (14.3) | 3 (8.3) | |||
| Double-class refractory, n (%)* | 42 (66.7) | 10 (71.4) | 27 (75.0) | |||
| Triple-class refractory, n (%)† | 2 (3.2) | 10 (71.4) | 27 (75.0) | |||
| Prior IMID, n (%) | Exposed | Refractory‡ | Exposed | Refractory‡ | Exposed | Refractory‡ |
| Thalidomide | 32 (50.8) | 11 (17.5) | 9 (64.3) | 5 (35.7) | 16 (44.4) | 5 (13.9) |
| Lenalidomide | 63 (100) | 51 (81.0) | 14 (100) | 11 (78.6) | 36 (100) | 27 (75.0) |
| Pomalidomide | 23 (36.5) | 22 (34.9) | 6 (42.9) | 6 (42.9) | 13 (36.1) | 13 (36.1) |
| Prior PI, n (%) | Exposed | Refractory‡ | Exposed | Refractory‡ | Exposed | Refractory‡ |
| Bortezomib | 61 (96.8) | 37 (58.7) | 14 (100) | 10 (71.4) | 34 (94.4) | 24 (66.7) |
| Carfilzomib | 7 (11.1) | 7 (11.1) | 0 | 0 | 5 (13.9) | 5 (13.9) |
| Ixazomib | 2 (3.2) | 2 (3.2) | 0 | 0 | 2 (5.6) | 2 (5.6) |
| Prior monoclonal antibody, n (%) | Exposed | Refractory‡ | Exposed | Refractory‡ | Exposed | Refractory‡ |
| Daratumumab | 3 (4.8)§ | 2 (3.2) | 14 (100) | 14 (100) | 36 (100) | 36 (100) |
| Elotuzumab | 2 (3.2) | 2 (3.2) | 0 | 0 | 2 (5.6) | 2 (5.6) |
| Durvalumab | 6 (9.5) | 6 (9.5) | 0 | 0 | 6 (16.7) | 6 (16.7) |
| ISS at registration, n (%) | ||||||
| I | 14 (22.2) | 5 (35.7) | 8 (22.2) | |||
| II | 30 (47.6) | 2 (14.3) | 22 (61.1) | |||
| III | 14 (22.2) | 6 (42.9) | 2 (5.6) | |||
| Unknown | 5 (7.9) | 1 (7.1) | 4 (11.1) | |||
| Cytogenetic abnormalities¶, n (%) | ||||||
| t(4;14) | 1 (1.6) | 0 | 0 | |||
| t(14;16) | 1 (1.6) | 1 (7.1) | 0 | |||
| t(14;20) | 0 | 0 | 0 | |||
| del(17p) | 11 (17.5) | 2 (14.3) | 3 (8.3) | |||
| amp(1q) | 25 (39.7) | 7 (50.0) | 13 (36.1) | |||
| del(1p) | 5 (7.9) | 3 (21.4) | 2 (5.6) | |||
| del(13q) | 17 (27) | 7 (50.0) | 7 (19.4) | |||
| Cytogenetic risk profile#, n (%) | ||||||
| High-risk | 36 (57.1) | 8 (57.1) | 18 (50.0) | |||
| Standard-risk | 14 (22.2) | 2 (14.3) | 11 (30.6) | |||
| Not available | 13 (20.6) | 4 (28.6) | 7 (19.4) | |||
| Laboratory values at baseline, median (range) | ||||||
| Absolute neutrophil count, ×109/L | 2.92 (0.60-8.87) | 2.89 (1.67-8.00) | 3.36 (0.90-8.27) | |||
| Hemoglobin level, mmol/L | 7.0 (4.8-8.9) | 7.1 (5.0-8.4) | 7.3 (6.0-9.3) | |||
| Platelet count, ×109/L | 168 (34-479) | 146 (50-445) | 181 (32-600) | |||
| Creatinine, µmol/L | 88 (53-228) | 91 (61-140) | 88 (62-140) | |||
| Calcium, mmol/L** | 2.41 (2.05-2.95) | 2.35 (2.19-2.56) | 2.42 (2.15-2.60) | |||
| LDH, U/L | 204 (119-1356) | 199 (145-279) | 179 (142-641) | |||
| Bone marrow plasma cell percentage in biopsy (median, range)†† | 50 (0-100) | NA | NA | |||
Double-class refractory is defined as both IMiD and PI refractory disease.
Triple-class refractory is defined as IMID, PI, and CD38-targeting antibody refractory disease.
Refractory disease is defined as PD during therapy, no response (<PR), or PD within 60 days of stopping treatment, according to the International Uniform Response Criteria for Multiple Myeloma.
3 patients had previously been treated with daratumumab 16, 42, and 48 months before registration.
As determined by fluorescence in situ hybridization or single nucleotide polymorphism array on purified MM cells before start of daratumumab treatment.
According to the criteria proposed by Sonneveld et al. Blood 2016.46 High risk disease is defined by the presence of t(4;14), t(14;16), t(14;20), del(17/17p), and/or gain(1q).
Calcium corrected for serum albumin using the following formula: corrected calcium = calcium measured + ((40 − albumin) × 0.02).
Based on data from 39 patients (62%).