Table 2.
Toxicities according to study periods: induction therapy, high-dose melphalan and maintenance therapy.
| Events | S1 n/% | S2 n/% | S3 n/% | p |
|---|---|---|---|---|
| Induction therapy | N = 349 | N = 108 | N = 141 | |
| Any AE/SAE | 205/58.7 | 78/72.2 | 96/68.1 | 0.02 |
| Infections and infestations (≥2°, SOC) | 56/16.0 | 24/22.2 | 30/21.3 | 0.20 |
| Blood and lymphatic system disorders (≥3°, SOC) | 66/18.9 | 28/25.9 | 35/24.8 | 0.16 |
| Gastrointestinal disorders (≥3°, SOC) | 16/4.6 | 8/7.4 | 18/12.8 | 0.008 |
| Cardiac disorders (≥2°, SOC) | 4/1.1 | 3/2.8 | 3/2.1 | 0.40 |
| Renal and urinary disorders (≥3°, SOC) | 11/3.2 | 2/1.9 | 4/2.8 | 0.89 |
| Neuropathy (≥2°, specific term) | 25/7.2 | 9/8.3 | 8/5.7 | 0.70 |
| Thromboembolic events (≥2°, specific term) | 9/2.6 | 5/4.6 | 6/4.3 | 0.44 |
| Leukocyto- and/or neutropenia (≥3°, specific term) | 73/20.9 | 35/32.4 | 32/22.7 | 0.05 |
| Thrombocytopenia (≥3°, specific term) | 14/4.0 | 7/6.5 | 8/5.7 | 0.45 |
| Anemia (≥3°, specific term) | 15/4.3 | 6/5.6 | 7/5.0 | 0.80 |
| Any SAE | 74/21.2 | 41/38.0 | 57/40.4 | <0.001 |
| SAE due to infections and infestations (SOC) | 20/5.7 | 16/14.8 | 14/9.9 | 0.01 |
| First MEL200/ASCT | N = 302 | N = 96 | N = 123 | |
| Any SAE | 43/14.2 | 16/16.7 | 42/34.1 | <0.001 |
| SAE due to infections and infestations (SOC) | 22/7.3 | 10/10.4 | 19/15.4 | 0.04 |
| Second MEL200/ASCT | N = 104 | N = 22 | N = 29 | |
| Any SAE | 20/19.2 | 6/27.3 | 9/31.0 | 0.33 |
| SAE due to infections and infestations (SOC) | 11/10.6 | 4/18.2 | 3/10.3 | 0.52 |
| Lenalidomide maintenance | N = 273 | N = 87 | N = 107 | |
| Any AE/SAE | 188/68.9 | 62/71.3 | 78/72.9 | 0.74 |
| Infections and infestations (≥2°, SOC) | 118/43.2 | 37/42.5 | 57/53.3 | 0.18 |
| Blood and lymphatic system disorders (≥3°, SOC) | 92/33.7 | 27/31.0 | 37/34.6 | 0.88 |
| Gastrointestinal disorders (≥3°, SOC) | 13/4.8 | 6/6.9 | 11/10.3 | 0.13 |
| Cardiac disorders (≥2°, SOC) | 1/0.4 | 0/0.0 | 3/2.8 | 0.07 |
| Renal and urinary disorders (≥3°, SOC) | 2/0.7 | 1/1.1 | 2/1.9 | 0.48 |
| Neuropathy (≥2°, specific term) | 12/4.4 | 3/3.4 | 4/3.7 | 1.0 |
| Thromboembolic events (≥2°, specific term) | 7/2.6 | 6/6.9 | 5/4.7 | 0.14 |
| Leukocyto- and/or neutropenia (≥3°, specific term) | 92/33.7 | 29/33.3 | 30/28.0 | 0.56 |
| Thrombocytopenia (≥3°, specific term) | 23/8.4 | 7/8.0 | 18/16.8 | 0.05 |
| Anemia (≥3°, specific term) | 5/1.8 | 2/2.3 | 2/1.9 | 0.90 |
| Any SAE | 81/29.7 | 30/34.5 | 50/46.7 | 0.01 |
| SAE due to infections and infestations (SOC) | 48/17.6 | 13/14.9 | 31/29.0 | 0.02 |
Detailed listing of (serious) adverse events according to treatment phases: induction therapy, MEL200/ASCT and maintenance therapy with respect to the three age groups ≤60 years (S1), 61–65 years (S2) and 66–70 years (S3). Adverse events were recorded applying the NCI CTCAE criteria (version 4.0, ≥2° for infections, cardiac disorders, neuropathy or thromboembolic events or if an serious adverse event occurred, otherwise, only if ≥3°) and systematically analyzed using the MedDRA terminology. For MEL200/ASCT, only SAE were available. Specific AE/SOC terms are presented if considered relevant and may subsummarize different primary terms according to MedDRA.
Bold p values are statistically significant.
AE adverse event, SAE serious AE, NCI CTCAE National Cancer Institute Common Terminology Criteria for Adverse Events, SOC System Organ Class (according to MedDRA terminology).