Table 1.

Completed clinical trials of blinatumomab in the treatment of B-cell malignancies

Study, NCT number (publication[s])	Phase	Objective(s)	No. of patients /age	Indication	BLI treatment regimen	Comparator	Efficacy outcomes	AEs with BLIf
								Any grade	Grade ≥ 3	AEs of special interest
NCT01209286 Topp et al. (2014)	II	Dose-finding	36/adults	R/R B-ALL	Continuous IVI for 4 wks of 6-wk cycle 5 μg/m2/day for 1 wk, then 15 μg/m2/day	None	CR/CRh: 69% [MRD: 88%; HSCT: 52%] mOS: 9.8 mo mRFS: 7.6 mo	Pyrexia 81% Fatigue 50% Headache 47% Tremor 36% Leukopenia 19%	Leukopenia 4% Thrombocytopenia 9%	Neuro AEsa 17% G4 CRS 6%
NCT01466179 Topp et al. (2015)	II	Efficacy and safety	189/adults	Ph–R/R B-ALL	Continuous IVI for 4 wks of 6-wk cycle 9 μg/day for the first 7 days, then 28 μg/day for 21 days	None	CR/CRh: 43% [MRD: 82%; HSCT: 40%] mOS: 6.1 mo mRFS: 5.9 mo	Pyrexia 60% Headache 34% Febrile neutropenia 28% Peripheral oedema 26% Nausea 24% Hypokalaemia 24% Constipation 21% Anaemia 20%	Febrile neutropenia 25% Neutropenia 16% Anaemia 14%	G3 neuro AEs 11% G3 CRS 2%
TOWER, NCT02013167 Kantarjian et al. (2017)	III	Efficacy and safety	405/adults	Ph–R/R B-ALL	Induction and consolidation: Continuous IVI for 4 wks of 6-wk cycle 9 μg/day for the first 7 days, then 28 μg/day for 21 days Maintenance: Continuous IVI for 4 wks every 12 wks	Standard CTx (SC)b	mOS: BLI: 7.7 mo; SC: 4.0 mo P = 0.01 CR/CRh: BLI: 42%; SC: 20% P < 0.001	Pyrexia 60% Headache 29% Anaemia 26% Febrile neutropenia 24% Diarrhoea 22% Neutropenia 20% Nausea 19% Thrombocytopenia 18% Hypokalaemia 17%	Febrile neutropenia 21% Neutropenia 18%	≥ G3 neuro AEs 9%  ≥ G3 CRS 3%C
NCT02393859 Locatelli et al. (2021)	III	Efficacy and safety	108/ < 18 yr	Relapsed B-ALL (consolidation therapy)	Continuous IVI for 4 weeks (1 cycle only) 15 μg/m2/day	CTx	EFS:d BLI 69%; chemotherapy 43% P < 0.001 ACM: BLI 15%; chemotherapy 30%	Pyrexia 81% Nausea 41% Headache 35% Stomatitis 35% Vomiting 30% Serious AEs: 24% [Chemotherapy: 43%]	Overall: 57.4% [Chemotherapy: 82.4%] Thrombocytopenia 19% Stomatitis 19% Neutropenia 17% Anaemia 15%	Neuro AEs 48% [≥ G3 6%]
NCT02101853 Brown et al. (2021)	III	Efficacy and safety	208/ ≤ 30 yr	Relapsed B-ALL (consolidation therapy pre-HSCT)	Continuous IVI for 4 weeks (two cycles separated by 7-day break) 15 μg/m2/day	CTx	2-yr DFS: BLI 54% CTx 39% 2-yr OS: BLI 71% CTx 58%	First cycle: Anaemia 76% WBC decreased 66% ALT increased 64% Fever 53% Neutrophil count decreased 50% Serious AEs:e Infection 15% Febrile neutropenia 5% Sepsis 2% Mucositis 1%	First cycle: Anemia 15% WBC decreased 25% Neutrophil count decreased 33% Lymphocyte count decreased 36%	First cycle: CRS 22% [≥ G3 1%] Encephalopathy 11% [≥ G3 6%] Seizure 4% [≥ G3 1%]

ACM all-cause mortality, AE adverse event, ALT alanine aminotransferase, B-ALL B-cell acute lymphoblastic leukaemia, BLI blinatumomab, CR complete remission/response, CRh CR with partial haematological recovery, CRS cytokine release syndrome, CTx chemotherapy, DFS disease-free survival, EFS event-free survival, FLAG Fludarabine, cytarabine (Ara-C) and Granulocyte colony-stimulating factor, GX Grade X, HSCT haematopoietic stem cell transplantation, IVI intravenous infusion, mo months, (m)OS (median) overall survival, MRD minimal residual disease, mRFS median relapse-free survival, neuro neurological, Ph– Philadelphia chromosome-negative, R/R relapsed/refractory, WBC white blood cell, wk week, yr year(s)

^aNervous system or psychiatric disorders requiring treatment interruption or permanent discontinuation

^bInvestigator’s choice between FLAG (± anthracycline), high-dose cytarabine, high-dose methotrexate, and clofarabine

^cCRS of any grade was reported in 14% of blinatumomab recipients

^dEvents: relapse, death, second malignancy or failure to achieve complete remission over a median follow-up period of 22.4 mo

^eCorresponding rates in the chemotherapy arm were: infection, 65%; febrile neutropenia, 58%; sepsis, 27%; and mucositis, 28%

^fSelected AEs only. For full details, refer to the original publication