Unique toxicities of novel agents for B-cell ALL
| Drug . | Toxicity . | Clinical trials . | ||||||
|---|---|---|---|---|---|---|---|---|
| Inotuzumab | Phase 212 | Phase 1/213 | Phase 314 | |||||
| N = 90; median 39.5 y (range, 4-84 y) | N = 72; median 45 y (range, 20-79 y) | N = 109; median 47 y (range, 18-78 y) | ||||||
| Hyperbilirubinemia | Grade 1-2: 5% (w); 24% (sd) | Grade 1-2: 10% | Grade 1-2: 11% | |||||
| Grade ≥3: 0 (w); 41% (sd) | Grade ≥3: 0 | Grade ≥3: 4% | ||||||
| Liver enzyme elevation | Grade 1-2: 22% (w); 55% (sd) | Grade 1-2: 32% | Grade 1-2: 33% | |||||
| Grade ≥3: 5% (w); 2% (sd) | Grade ≥3: 6% | Grade ≥3: 8% | ||||||
| SOS | 7% (w) and 23% (sd) undergoing HCT | 8% undergoing HCT; 4% not undergoing HCT | 22% undergoing HCT; 8% not undergoing HCT | |||||
| Blinatumomab | Phase 235 | Phase 237 | Phase 236 | Phase 338 | Phase 239 | |||
| N = 21; median age 47 y (range, 20-77 y) | N = 36; median age 32 y (range, 18-77 y) | N = 189; median age 39 y (range, 18-79 y) | N = 267; mean age 40.8 y (range, 18-80 y) | N = 45; median age 55 y (range, 23-78 y) | ||||
| CRS | NA | Grade 1-2: NA | Grade 1-2: NA | Grade 1-2: 9% | Grade 1-2: 7% | |||
| Grade ≥3: 6% | Grade ≥3: 2% | Grade ≥3: 5% | Grade ≥3: 0 | |||||
| Neurotoxicity | 20% (grades not specified) | Grade 1-2: 22% | Grade 1-2: 39% | Grade 1-2: 36% | Grade 1-2: 44% | |||
| Grade ≥3: 14% | Grade ≥3: 13% | Grade ≥3: 9% | Grade ≥3: 7% | |||||
| Hypogammaglobulinemia | 24% | 8% | NA | 6% | NA | |||
| CAR-T | Phase 249 | Phase 150 | Phase 259 | Phase 151 | ||||
| N = 30; median age 14 y (range, 5-16 y) | N = 92 (treated =75); median age 11 y(range, 3-23 y) | N = 21; median age 13 y (range, 5-27 y) | N = 30; median age 39.5 y (range, 20-73 y) | N = 83 (treated =53); median age 44 y(range, 23-74 y) | ||||
| CRS | Grade 1-2: 73% | Grade 1-2: 43% | Grade 1-2: 48% | Grade 1-2: 60% | Grade 1-2: 59% | |||
| Grade ≥3: 27% | Grade ≥3: 36% | Grade ≥3: 28% | Severe: 23% (grade 5 = 3%) | Grade ≥3: 26% (grade 5 = 2%) | ||||
| Neurotoxicity | 43% (grades not specified) | Grade 1-2: 27% | Grade 1-2: 38% | Grade 1-2: 0 | Grade 2: 2% | |||
| Grade ≥3: 13% | Grade ≥3: 5% | Grade ≥3: 50% (grade 5 = 3%) | Grade ≥3: 42% | |||||
| Hypogammaglobulinemia | 90% (100% responders) | 81% (100% responders) | NA | NA | NA | |||
| Drug . | Toxicity . | Clinical trials . | ||||||
|---|---|---|---|---|---|---|---|---|
| Inotuzumab | Phase 212 | Phase 1/213 | Phase 314 | |||||
| N = 90; median 39.5 y (range, 4-84 y) | N = 72; median 45 y (range, 20-79 y) | N = 109; median 47 y (range, 18-78 y) | ||||||
| Hyperbilirubinemia | Grade 1-2: 5% (w); 24% (sd) | Grade 1-2: 10% | Grade 1-2: 11% | |||||
| Grade ≥3: 0 (w); 41% (sd) | Grade ≥3: 0 | Grade ≥3: 4% | ||||||
| Liver enzyme elevation | Grade 1-2: 22% (w); 55% (sd) | Grade 1-2: 32% | Grade 1-2: 33% | |||||
| Grade ≥3: 5% (w); 2% (sd) | Grade ≥3: 6% | Grade ≥3: 8% | ||||||
| SOS | 7% (w) and 23% (sd) undergoing HCT | 8% undergoing HCT; 4% not undergoing HCT | 22% undergoing HCT; 8% not undergoing HCT | |||||
| Blinatumomab | Phase 235 | Phase 237 | Phase 236 | Phase 338 | Phase 239 | |||
| N = 21; median age 47 y (range, 20-77 y) | N = 36; median age 32 y (range, 18-77 y) | N = 189; median age 39 y (range, 18-79 y) | N = 267; mean age 40.8 y (range, 18-80 y) | N = 45; median age 55 y (range, 23-78 y) | ||||
| CRS | NA | Grade 1-2: NA | Grade 1-2: NA | Grade 1-2: 9% | Grade 1-2: 7% | |||
| Grade ≥3: 6% | Grade ≥3: 2% | Grade ≥3: 5% | Grade ≥3: 0 | |||||
| Neurotoxicity | 20% (grades not specified) | Grade 1-2: 22% | Grade 1-2: 39% | Grade 1-2: 36% | Grade 1-2: 44% | |||
| Grade ≥3: 14% | Grade ≥3: 13% | Grade ≥3: 9% | Grade ≥3: 7% | |||||
| Hypogammaglobulinemia | 24% | 8% | NA | 6% | NA | |||
| CAR-T | Phase 249 | Phase 150 | Phase 259 | Phase 151 | ||||
| N = 30; median age 14 y (range, 5-16 y) | N = 92 (treated =75); median age 11 y(range, 3-23 y) | N = 21; median age 13 y (range, 5-27 y) | N = 30; median age 39.5 y (range, 20-73 y) | N = 83 (treated =53); median age 44 y(range, 23-74 y) | ||||
| CRS | Grade 1-2: 73% | Grade 1-2: 43% | Grade 1-2: 48% | Grade 1-2: 60% | Grade 1-2: 59% | |||
| Grade ≥3: 27% | Grade ≥3: 36% | Grade ≥3: 28% | Severe: 23% (grade 5 = 3%) | Grade ≥3: 26% (grade 5 = 2%) | ||||
| Neurotoxicity | 43% (grades not specified) | Grade 1-2: 27% | Grade 1-2: 38% | Grade 1-2: 0 | Grade 2: 2% | |||
| Grade ≥3: 13% | Grade ≥3: 5% | Grade ≥3: 50% (grade 5 = 3%) | Grade ≥3: 42% | |||||
| Hypogammaglobulinemia | 90% (100% responders) | 81% (100% responders) | NA | NA | NA | |||
CRS, cytokine release syndrome; HCT, allogeneic stem cell transplantation; NA, not available; sd, single dose; w, weekly