Table 2.
Clinical advances of blinatumomab in the treatment of B-cell malignancies
| Study/NCT identifier | Phase | Indications | Number of patients | Blinatumomab dosing | Efficacy | Toxicity | Reference |
|---|---|---|---|---|---|---|---|
| GMALL (original study NCT00198991, follow-up study NCT00198978) | 2 | Adults (≥18 years) with MRD-positive B- ALL | 21 (20 evaluable for response) | Continuous IV infusion at a dose of 15 μg/m2 /d | MRD-negative response rate: 80% (16/20) 5-year RFS rate: 50% (10/20) Median RFS: 19.1 months in 16 MRD responders; 3.2 months in 4 nonresponders CR in HSCT patients: 5/9 CR in non-HSCT patients: 5/11 | Grade ≥ 3 AEs: 81% Grade 3 CNS AEs: 19% | [32–34] |
| BLAST (NCT01207388). | 2 | Adults with MRD-positive B-ALL | 116 (113 evaluable for response) | Continuous IV infusion at a dose of 15 μg/m2 /d | MRD-negative response rate: 78% (88/113) 18 months RFS rate: 54% Median RFS: 18.9 months Median OS: 36.5 months 25% patients without HSCT after blinatumomab remained in continuous CR 49% with HSCT remained in continuous CR |
Grade ≥ 3 AEs: 60% Any grade CRS: 3% Grade ≥ 3 CRS: 2% Any grade CNS AEs: 53% Grade ≥ 3 CNS AEs: 13% |
[35, 36] |
| NCT02412306 | 1/2 | Japanese adults with R/R Ph-negative B-ALL | 26 | Continuous IV infusion at a dose of 9 μg/m2 /d for the first 7 days and 28 μg/m2 /d thereafter |
Phase 1b: CR/CRh rate: 80% (4/5) MRD-negative response rate in responders: 100% (4/4) Phase 2: CR/CRh rate: 38% (8/21) MRD-negative response rate in responders: 38% (3/8) Median RFS: 5 months |
Grade ≥ 3 AEs: 96% Any grade CRS: 46% Grade ≥ 3 CRS: 4% Any grade CNS AEs: 46% Grade ≥ 3 CNS AEs: 5% |
[37] |
| NCT01209286 | 2 | Adults with R/R Ph-negative B-ALL | 36 | Continuous IV infusion at a dose of 5–30 μg/m2 /d | CR/CRh rate: 69%(25/36) MRD-negative response rate in responders: 88% (22/25) Median OS: 9.8 months Median RFS: 7.6 months |
CNS AEs requiring intervention: 17% Grade ≥ 3 CRS: 6% |
[38] |
| NCT01466179 | 2 | Adults (≥18 years) with R/R Ph-negative B-ALL | 189 | Continuous IV infusion from 9 to 28 μg/m2/d | CR/CRh rate: 43%(81/189) MRD-negative response rate in responders: 82% (60/73) Median OS: 6.1 months Median RFS: 5.9 months |
Grade ≥ 3 AEs: 83% Grade ≥ 3 CRS: 2% Any grade CNS AEs: 52% Grade ≥ 3 CNS AEs: 13% |
[39] |
| TOWER (NCT02013167) | 3 | Adults (≥18 years) with R/R Ph-negative B-ALL | 405 (271 for blinatumomab, 134 for chemotherapy) | Continuous IV infusion from 9 to 28 μg/m2/d | Median OS: 7.7 vs. 4.0 months CR rate: 34% vs. 16%; CR/CRh/CRi rate: 44% vs. 25% 6-month EFS: 31% vs. 12% Median DOR: 7.3 vs. 4.6 months |
Grade ≥ 3 AEs: 87% vs. 92% Grade ≥ 3 CNS AEs: 9.4% vs.8.3% Grade ≥ 3 CRS: 4.9% vs. 0% (blinatumomab vs. chemotherapy) |
[40] |
| RIALTO (NCT02187354) | Expanded Access | Children (≤17 years) with R/R B-ALL | 110 (98 evaluable for response) |
≤ 25% blasts: 15 μg/m2/d > 25% blasts: 5 μg/m2/d for first 7 days, 15 μg/m2/d thereafter, |
CR rate: 59% (58/98) MRD-negative response rate in responders: 79% (46/58) Median OS:13.1 months Median RFS: 8.5 months 62% (36/58) proceeded to HSCT after achieving CR |
Grade ≥ 3 AEs: 65% Grade ≥ 3 CRS: 3% Any grade CNS AEs: 42% Grade ≥ 3 CNS AEs: 5.5% |
[41] |
| MT103–205 (NCT01471782) | 1/2 | Children (≤17 years) with R/R B-ALL | 94 (70 evaluable for response) | Continuous IV infusion from 5 to 15 μg/m2/d | CR rate: 39% (27/70) MRD-negative response rate in responders: 52% (14/27) 48% (13/27) proceeded to HSCT after achieving CR |
Grade ≥ 3 AEs: 87% Any grade CRS: 11% Grade ≥ 3 CRS: 6% Any grade CNS AEs: 24% Grade ≥ 3 CNS AEs: 4% |
[42] |
| NCT02000427 | 2 | Adults (≥18 years) with R/R Ph-positive B-ALL | 45 | Continuous IV infusion from 9 to 28 μg/m2/d | CR/CRh rate: 36%(16/45) MRD-negative response rate in responders: 88% (14/16) Median OS: 7.1 months Median RFS: 6.7 months 44% (7/16) proceeded to HSCT after achieving CR |
Grade ≥ 3 AEs: 82% Any grade CRS: 7% Grade ≥ 3 CNS AEs: 7% |
[43] |
| MT103–104 (NCT00274742) | 1 | Adults (≥18 years) with R/R B-NHL | 76 | Dose-escalation: 0.5–90 μg/m2/d Dose-expansion: 60 μg/m2/d |
Patients with dose of 60 μg/m2/d: ORR: 69% across NHL subtypes and 55% for DLBCL Median DOR: 404 days Median OS in overall population: 4.6 years Median OS in responders: 7.7 years Median OS in nonresponders: 1.1 years |
Grade 3, 4, and 5 AEs: 90, 66, and 4%, respectively Any grade CNS AEs: 71% Grade 3 CNS AEs: 22% |
[44, 45] |
| NCT02910063 | 2 | Adults with R/R B-NHL | 41 | Continuous IV infusion from 9 to 28 to 112 μg/d |
ORR: 37% (15/41) including CMR: 22% (9/41) and PMR: 15% (6/41) HSCT was performed in 53.3% (8/15) responders. |
Grade ≥ 3 AEs: 71% Grade ≥ 3 CRS: 2% Any grade CNS AEs: 56% Grade ≥ 3 CNS AEs.: 24% |
[46] |
| NCT01741792 | 2 | Adults with R/R B-DLBCL | 25 (21 evaluable for response) |
Cohort I + III: Stepwise dose 9 to 28 to 112 μg/d Cohort II: Flat dose 112 μg/d |
Patients with dose of 112 μg/d at least 1 week: ORR: 43% (9/21) CR rate: 19% (4/21) |
Cohort I: n = 23 Grade ≥ 3 AEs: 95.7% Any grade CRS: 0% Grade ≥ 3 CNS AEs: 22% Cohort II: n = 2 Grade ≥ 3 CNS AEs: 100% |
[47] |
MRD Minimal residual disease, B-ALL B-precursor acute lymphoblastic leukemia, IV Intravenous, HSCT Allogeneic hematopoietic stem cell transportation, AEs Adverse events, R/R Refractory/relapsed, CRS Cytokine release syndrome, OS Overall survival, RFS Relapse-free survival, CR Complete remission, CRh Complete remission with partial hematologic recovery, CRi Complete remission with incomplete hematological recovery, Ph Philadelphia chromosome, NHL Non- Hodgkin lymphoma, DLBCL Diffuse large B cell lymphoma, DLT Dose-limiting toxicity, DOR Duration of remission, EFS Event-free survival, ORR Objective response rate, CMR Complete metabolic response