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. 2017 Jul 19;10:3567–3578. doi: 10.2147/OTT.S103470

Table 1.

Published clinical trials on blinatumomab

Study indication, phase, clinical trial identifier, sponsor Patient characteristics Blinatumomab dosing Outcome data Rate of cytokine-release syndrome and neurotoxic events
Adult R/R B-ALL, randomized controlled (blinatumomab vs chemotherapy), multicenter international, Phase III, TOWER, NCT02013167, Amgen30 405 patients, blinatumomab =271 patients, chemotherapy =134 patients
• Relapse within 12 mo after CR1 or allogenic HSCT or nonresponse to first salvage therapy or ≥2 relapse
• Bone marrow ≥5% blasts
• Only Ph-neg. patients
• No active CNS disease
• 140/403 (35%) patients had previous allogenic HSCT
• Mean age 40.9 years
Blinatumomab:
• Continuous infusion with 9 µg/d for 1 week followed by 28 µg/d for 3 weeks, next cycle after 2 weeks off starting with 28 µg/d (for 4 weeks)
• Prior dexamethasone
Both groups:
• Up to 5 cycles/blocks blinatumomab/chemotherapy for induction and consolidation, maintenance therapy when indicated
Primary outcome for blinatumomab vs chemotherapy:
• Median OS 7.7 mo vs 4.0 mo after median follow-up of 11.7 mo, P=0.01
Secondary outcomes for blinatumomab vs chemotherapy:
• CR/CRh in 44% vs 25%, P<0.001
• 33% vs 12% became MRD negative
• Median RFS 7.3 mo vs 4.6 mo
• 6 mo EFS 31% vs 12%
• In both groups, 24% of the patients proceeded to allogenic HSCT
• OS curves are separating within 3 mo with longer survival for blinatumomab and are converging again after 15 mo
Blinatumomab vs chemotherapy:
• All AEs > grade (°)II=87% vs 92%
• CRS >°II=13/267 (5%) vs 0/109
• Neurotoxicity >°II=25/267 (9%) vs 9/109 (8%)
Adult R/R B-ALL, single arm, multicenter international, Phase II, NCT01466179, NCT02003612, Amgen28,29 189 patients
• Relapse within 12 mo after CR1 or allogenic HSCT or nonresponse to first salvage therapy or ≥2nd relapse
• Bone marrow ≥10% blasts
• Only Ph-neg. patients
• No previous/active CNS disease
• 64/189 (34%) patients had previous allogenic HSCT
• Median age of 39 years
Continuous infusion with 9 µg/d for 1 week followed by 28 µg/d for 3 weeks, next cycle after 2 weeks off starting with 28 µg/d (for 4 weeks)
In case of high leukemic burden prior dexamethasone
Primary outcome:
• 81/189 (43%) patients achieved CR/CRh within 2 treatment cycles
Secondary outcomes:
• 60/181 (33%) patients became MRD negative within 2 treatment cycles (59 after the first, 1 patient after the second cycle)
• 32/81 (40%) patients with CR/CRh proceeded to allogenic HSCT
After follow-up of a median of 8.9 mo:
• In 81 patients with CR/CRh, median RFS was 5.9 mo with 6.9 mo for MRD responders vs 2.3 mo for MRD nonresponders
• Median OS for all 189 patients: 6.1 mo with a median follow-up of 9.8 mo
• CRS >°II=2/189 (2%)
• Neurotoxicity >°II=20/189 (11%); 87% of neurological events occurred in first cycle
Pediatric R/R B-ALL, single arm, multicenter international, Phase I/II, NCT01471782, Amgen7 46 Phase I, 44 patients Phase II
• Bone marrow ≥25% blasts
• <18 years
• 70 patients received final dosing = eligible for response evaluation
 ○ Median age of 8 years
Phase I: escalating dosing;
Phase II: continuous infusion with 5 µg/m2/d for 1 week followed by 15 µg/m2/d for 3 weeks, second cycle after 2 weeks off starting with 15 µg/m2/d (for 4 weeks)
Prior dexamethasone
Primary outcome Phase I:
• 4 DLT: 3 CRS °IV, 1 respiratory failure
Primary outcome for the 70 patients who received final dosing:
• 27/70 (39%) patients achieved CR within two cycles
Secondary outcomes:
• 14/70 (20%) became MRD negative within two cycles
After follow-up of a median of 23.1 mo:
• Median RFS =4.4 mo in the CR group
• Median RFS =7.3 mo in MRD response group
• 2/3 patients with Ph+ ALL achieved CR
• Median OS =7.5 mo
Phase I:
• CRS >°II=3/49 (6%)
Phase II:
• CRS >°II=5/70 (7%)
• Neurotoxicity >°II=0/70
• 2 patients (3%) with II° seizure
Adult R/R B-ALL, single arm, multicenter in Germany (GMALL group), Phase I/II, NCT01209286, Amgen37,53 36 patients evaluable
• M2/3 bone marrow with >5% blasts
• Only Ph-neg. patients
• No previous/active CNS disease
• 15/36 (42%) patients had previous allogenic HSCT
• Median age of 32 years
Phase I: escalating dosing;
Phase II: continuous infusion with 5 µg/m2/d for 1 week followed by 15 µg/m2/d for 3 weeks, next cycle after 2 weeks off starting with 15 µg/m2/d (for 4 weeks)
Phase II: prior dexamethasone
Primary outcome:
• 25/36 (69%) patients achieved CR/CRh
• 8 of 15 (52%) patients achieved CR/CRh after allogeneic HSCT
Secondary outcomes:
• 22/36 (61%) patients became MRD negative
• 13/25 (52%) responders underwent allogeneic HSCT (2 relapses afterwards, 6 TRM)
• 12/25 (48%) responders did not proceed to allogeneic HSCT (8 relapses)
After follow-up of a median of 28.9 mo:
• 12 patients in CR, resulting in an estimated RFS of 61%
• Of 9 patients after allogenic HSCT, 6 were in CR, 2 had relapsed, 1 died due to TRM
CRS >°II=2/36 (6%)
Neurotoxicity >°II=5/36 (14%); 4/5 within the first treatment week
• 3 encephalopathy (tremor, aphasia, confusion)
• 2 seizures
• 1 patient with II° seizure
• All events were reversible
Adult B-ALL with CR but persisting/relapsing MRD, single arm, multicenter in Germany (GMALL group), Phase II, NCT00198991, NCT00198978, Amgen26,42,54 20/21 patients evaluable
• 15 with persisting MRD
• 5 with relapsed MRD
• Including 5 cases of Ph+ ALL nonresponding to TKI
• No prior HSCT
• Median age of 47 years
15 µg/m2/d for 4 weeks, next cycle after 2 weeks off, up to
4 cycles
4 initial cycles, followed by up to
3 additional cycles
No prior dexamethasone
Primary outcome:
• 16/20 (80%) patients became MRD negative, all within the first treatment cycle
• 3/5 patients with Ph+ ALL responded
• 9 patients underwent allogenic HSCT
After follow-up of a median of 50.8 mo:
• 10 patients in CR, resulting in long-term RFS of 50%
• Of 9 patients after allogenic HSCT, 5 were in CR, 3 had relapsed, 1 died due to TRM
• Of 11 patients w/o allogenic HSCT, 5 were in CR, 5 had relapsed, 1 withdrew from trial
• In 2/6 relapses patients the ALL became CD19 neg.
• 2/6 relapses were extramedullary (CD19+)
CRS >°II=0
Neurotoxicity >°II=1 (generalized seizure, completely reversible)

Abbreviations: AE, adverse event; ALL, acute lymphoblastic leukemia; CNS, central nervous system; CR, complete remission; CRh, complete remission with incomplete hematological recovery; CRS, cytokine-release syndrome; DLT, dose limiting toxicity; EFS, event-free survival; GMALL, German Multicenter Study Group for Adult ALL; HSCT, hematopoietic stem cell transplantation; mo, months; MRD, minimal residual disease; OS, overall survival; Ph, Philadelphia chromosome; RFS, relapse-free survival; R/R ALL, relapsed or refractory acute lymphoblastic leukemia; TKI, tyrosine kinase inhibitors (imatinib and/or dasatinib); TRM, therapy-related mortality.