Safety of newer agents: summary of adverse events
| Agent (Reference) . | Summary . |
|---|---|
| Pomalidomide (40, 41) | Major toxicity: neutropenia (27%-66% grade 3-4), grade 3-4 anemia and thrombocytopenia less common (30%) |
| Nonhematologic toxicity: thromboembolic events similar to other IMIDs. Less constipation fatigue, skin rash than with thalidomide | |
| Treatment-emergent neuropathy: rare | |
| Carfilzomib (42) | Most frequent AEs any grade: fatigue, 55.5%; anemia, 47%; nausea, 45% |
| Hematologic toxicity grade 3-4: thrombocytopenia, 23%; anemia, 22%; lymphopenia, 18%; pneumonia, 10% | |
| Peripheral neuropathy: 14% any grade, 6% grades 2-3 (85% previous neuropathy) | |
| Cardiac AEs: 22% (leading to 4.4% treatment interruption) including: CHF, 7%; HTA, 14% | |
| Renal AEs: 13% worsening renal function; 5.5% renal failure | |
| Panobinostat (43, 44) | In phase 1 studies, grade 3-4: anemia, 18%; neutropenia, 21-32%; thrombocytopenia, 26-42%; fatigue, 21% |
| In combination with bortezomib, the major nonhematologic AEs was diarrhea | |
| Elotuzumab (32, 45) | Well tolerated in phase 1 trial (MTD not reached), mostly grade 1-2 AEs (chills, fatigue, pyrexia, cough, headache) |
| Phase 2 studies performed in combination with other agents | |
| Ixazomib (46, 47) | Common AEs in phase 1 studies: nausea, 38%-42%; thrombocytopenia, 42%; fatigue, 37%-40% |
| Grade 3 or more: thrombocytopenia, 37%; neutropenia, 17%-26%; diarrhea, 23% | |
| Peripheral neuropathy: grade 1-2, 12%-20% | |
| Daratumumab (33-35) | Most frequent nonhematologic AE (mostly grade 1-2): fatigue, nausea, cough |
| Grade 3-4 hematologic AEs: anemia, 17%; thrombocytopenia, 8%; neutropenia, 7% | |
| Infusion-related reactions (60%-70% mostly during first infusion, usually grade 1-2): nasal congestion, cough, bronchospasm, pyrexia, chills, nausea, fatigue | |
| Interference with response assessment and blood typing |
| Agent (Reference) . | Summary . |
|---|---|
| Pomalidomide (40, 41) | Major toxicity: neutropenia (27%-66% grade 3-4), grade 3-4 anemia and thrombocytopenia less common (30%) |
| Nonhematologic toxicity: thromboembolic events similar to other IMIDs. Less constipation fatigue, skin rash than with thalidomide | |
| Treatment-emergent neuropathy: rare | |
| Carfilzomib (42) | Most frequent AEs any grade: fatigue, 55.5%; anemia, 47%; nausea, 45% |
| Hematologic toxicity grade 3-4: thrombocytopenia, 23%; anemia, 22%; lymphopenia, 18%; pneumonia, 10% | |
| Peripheral neuropathy: 14% any grade, 6% grades 2-3 (85% previous neuropathy) | |
| Cardiac AEs: 22% (leading to 4.4% treatment interruption) including: CHF, 7%; HTA, 14% | |
| Renal AEs: 13% worsening renal function; 5.5% renal failure | |
| Panobinostat (43, 44) | In phase 1 studies, grade 3-4: anemia, 18%; neutropenia, 21-32%; thrombocytopenia, 26-42%; fatigue, 21% |
| In combination with bortezomib, the major nonhematologic AEs was diarrhea | |
| Elotuzumab (32, 45) | Well tolerated in phase 1 trial (MTD not reached), mostly grade 1-2 AEs (chills, fatigue, pyrexia, cough, headache) |
| Phase 2 studies performed in combination with other agents | |
| Ixazomib (46, 47) | Common AEs in phase 1 studies: nausea, 38%-42%; thrombocytopenia, 42%; fatigue, 37%-40% |
| Grade 3 or more: thrombocytopenia, 37%; neutropenia, 17%-26%; diarrhea, 23% | |
| Peripheral neuropathy: grade 1-2, 12%-20% | |
| Daratumumab (33-35) | Most frequent nonhematologic AE (mostly grade 1-2): fatigue, nausea, cough |
| Grade 3-4 hematologic AEs: anemia, 17%; thrombocytopenia, 8%; neutropenia, 7% | |
| Infusion-related reactions (60%-70% mostly during first infusion, usually grade 1-2): nasal congestion, cough, bronchospasm, pyrexia, chills, nausea, fatigue | |
| Interference with response assessment and blood typing |
AE, adverse event; CHF, cardiac heart failure; HTA, hypertension; MTD, maximum tolerated dose.