Blinatumomab, a bispecific B-cell and T-cell engaging antibody, in the treatment of B-cell malignancies

Figures & data

Table 1. Reported clinical trials.

Primary Investigator	Indication	Phase	No. of patients	Treatment regimen	Response	Overall Survival
Goebeler et al. 2016^Citation23	Adult R/R B-NHL	I	76	Continuous infusion, escalating doses. MTD 60µg/m^2/day given in n = 35	At MTD: ORR FL = 80% MCL = 71% DLBCL = 55% Other = 50%	Not available (Median response duration 404 days)
Viardot et al. 2016^Citation24	Adult R/R DLBCL	II	25	Continuous infusion with weekly dose escalation, to target 112 µg/day	ORR 43%	5.0 months
Topp et al. 2011^Citation25	Adult MRD positive B-ALL	II	21	Continuous infusion 15 µg/m^2/day	80% MRD response	Not available (At median follow-up 50.8 months 50% still in remission)
Gökbuget et al. 2017^Citation28	Adult MRD positive B-ALL	II	116	Continuous infusion 15 µg/m^2/day	78% MRD response post cycle 1, 80% MRD response overall	36.4 months
Topp et al. 2014^Citation29	Adult R/R B-ALL	II	36	5–30 µg/m^2/day	69% CR/CRh (88% MRD response post cycle 1)	9.8 months
Topp et al. 2015^Citation31	Adult R/R B-ALL	II	189	9 µg/day for first week cycle 1, 28 µg/day thereafter	43% CR/CRh (82% MRD response)	6.1 months
Martinelli et al. 2015^Citation35	Adult Ph-positive R/R B-ALL	II	45	9 µg/day for first week cycle 1, 28 µg/day thereafter	CR/CRh 36% (86% MRD response)	7.1 months
Kantarjian et al. 2017^Citation33	Adult R/R B-ALL	III	405 (B: 271, SOC 134)	9 µg/day for first week cycle 1, 28 µg/day thereafter	B: 46% CR/CRh SOC: 28% CR/CRh	B: 7.8 months SOC: 4.0 months
Von Stackelberg et al. 2016^Citation36	Paediatric R/R B-ALL	I/II	70 (at recommended dosage)	In phase II: 5 µg/m^2/day for first week, 15 µg/m^2/day thereafter	38.6% CR	7.5 months

B-NHL: B-cell non Hodgkin lymphoma, B-ALL: B-cell precursor acute lymphoblastic leukaemia; FL: follicular lymphoma; MCL: mantle cell lymphoma; DLBCL: diffuse large B-cell lymphoma; R/R: relapsed or refractory; MRD: minimal residual disease; Ph: Philadelphia chromosome; ORR: overall response rate; CR: complete response; CRh: complete response with incomplete haematologic recovery; SOC: standard of care;

Table 2. Ongoing/planned clinical trials for B-NHL.

Phase	Sponsor	Clinical trial identifier	Condition	Concomitant medication	Primary end point
I	NCI	NCT02568553	R/R B-NHL	Lenalidomide	MTD
I	Washington University School of Medicine	NCT03072771	DLBCL post ASCT	BEAM ASCT	DLT/AE
Ib	Amgen	NCT02961881	R/R indolent B-NHL	None	DLT/AE
Ib	Amgen	NCT03340766	R/R DLBCL	Pembrolizumab	DLTs
II	Amgen	NCT02811679	R/R indolent B-NHL	None	ORR
II	Amgen	NCT03023878	High-risk DLBCL	Following up-front chemotherapy	Incidence/Severity AE
II	MDACC	NCT03121534	Richter’s transformation	Dexamethasone	ORR
II	Amgen	NCT03298412	MRD positive DLBCL post ASCT	None	MRD negativity
II/III	Amgen	NCT02910063	R/R aggressive B-NHL	None vs. IC chemotherapy	CMR

B-NHL: B-cell non Hodgkin lymphoma, DLBCL: diffuse large B-cell lymphoma; NCI: National Cancer Institute; MDACC: MD Anderson Cancer Centre; R/R: relapsed or refractory; MRD: minimal residual disease; IC: Investigator’s choice; ASCT: Autologous stem cell transplant; MTD: maximum tolerated dose; DLT: dose limiting toxicities; AE: adverse events ORR: overall response rate; CMR: complete metabolic response;

Table 3. Ongoing/Planned Clinical Trials for B-ALL.

Phase	Sponsor	Clinical trial identifier	Condition	Concomitant medication	Primary end point
Pilot study	SKCCC John Hopkins	NCT03114865	Adult B-ALL post ASCT	None	OS
I	NCI	NCT02879695	R/R B-ALL	Nivolumab or nivolumab + ipilimumab	Safety MTD
I/II	Amgen	NCT02412306	R/R B-ALL Japanese adults	None	Phase I: DLT Phase II: CR
I/II	City of Hope Medical Centre	NCT03512405	R/R adult B-ALL	Pembrolizumab	Phase I: safety Phase II: CR/CRh
I/II	University of California	NCT03160079	R/R B-ALL	Pembrolizumab	Phase I: safety Phase II: ORR
II	MDACC	NCT02877303	De novo B-ALL ≥ 14 yr.	Hyper-CVAD	RFS
II	MDACC	NCT02458014	Adult B-ALL in CR1/CR2 MRD positive	None	RFS
II	MDACC	NCT02807883	B-ALL post ASCT in adults	None	GvHD, NRM, graft failure
II	MDACC	NCT03263572	de novo Ph positive B-ALL	Ponatinib	CR
II	NCI	NCT02143414	De novo B-ALL ≥ 65 yr	Combination chemotherapy or dasatinib	CR
II	University of California	NCT02997761	R/R B-ALL	Ibrutinib	CR
II	GIMEMA	NCT02744768	Adults de novo Ph positive B- ALL	Dasatinib	CR
II	Goethe University	NCT03480438	De novo older adult B-ALL	Standard chemotherapy	CR MRD
II	JWG University Hospital	NCT03109093	Adults MRD positive B-ALL	None	MRD
II	MDACC	NCT03518112	R/R adult B-ALL	Mini-Hyper-CVD	EFS
II	PETHEMA	NCT03523429	De novo adult B-ALL	Standard chemotherapy	MRD
II	GIMEMA	NCT03367299	De novo adult B-ALL	Standard chemotherapy	MRD
II	HOVON	NCT03541083	De novo adult B-ALL	Standard chemotherapy	MRD
II/III	St Jude Children’s Research Hospital	NCT03117751	Refractory B-ALL	Standard combination chemotherapy	EFS
III	Amgen	NCT02393859	Paediatric B-ALL in first relapse	Chemotherapy Comparison with standard chemotherapy	EFS
III	NCI	NCT02101853	Patients 1–30 yr. B-ALL in first relapse	Comparison with standard chemotherapy ± ASCT	DFS
III	NCI	NCT02003222	De novo adult B-ALL	± standard chemotherapy	OS
III	Amgen	NCT03476239	R/R B-ALL Chinese adults	None	CR/CRh
III	Novartis	NCT03628053	R/R adult B-ALL	Tisagenlecleucel vs IC Blinatumomab/Inotuzumab	OS
III	Martin Schrappe	NCT03643276	De novo paediatric B-ALL	Standard chemotherapy	EFS/DFS

NCI: National Cancer Institute; MDACC: MD Anderson Cancer Centre; GIMEMA: Gruppo Italiano Malattie EMatologiche dell’Adulto; SKCCC: Sidney Kimmel Comprehensive Cancer Centre; JWG: Johann Wolfgang Goethe; HOVON: Stichting Hemato-Oncologie Volwassenen Nederland; PETHEMA: Programa para el Tratamiento de Hemopatías Malignas; B-ALL: B-cell precursor acute lymphoblastic leukaemia; R/R: relapsed or refractory; CR: complete response; MRD: minimal residual disease; Ph: Philadelphia chromosome; ASCT: Allogeneic stem cell transplant; IC: Investigator’s choice; DLT: dose limiting toxicities; ORR: overall response rate; MTD: maximum tolerated dose; RFS: relapse free survival; GVHD: graft versus host disease; NRM: non-relapse mortality; OS: overall survival; EFS: event free survival; DFS: disease free survival; CRh: complete response with incomplete haematologic recovery

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