Targeted treatment for chronic lymphocytic leukemia: clinical potential of obinutuzumab

Figures & data

Table 1 Targeted agents for the treatment of CLL

Agent	Mechanism of action	Phase of development
Obinutuzumab (GA101)	Glycoengineered type II anti-CD20 antibody	Approved; Phase III
Ibrutinib (PCI-32765)	Bruton tyrosine kinase inhibition	Approved; Phase III
CC-292	Bruton tyrosine kinase inhibition	Phase I/II
ONO-4059	Bruton tyrosine kinase inhibition	Phase I/II
Idelalisib (GS-1101)	Phosphatidylinositol-3-kinase δ inhibition	Approved; Phase III
IPI-145	Phosphatidylinositol-3-kinase δ inhibition	Phase II/III
Lenalidomide	Complex – microenvironment	Phase III
Venetoclax (ABT-199, GDC-0199)	Bcl-2 inhibition	Phase II/III
CAR T-cells	T cells with chimeric anti CD19 receptor	Phase II

Abbreviation: CLL, chronic lymphocytic leukemia.

Figure 1 Mechanisms of action of anti-CD20 monoclonal antibodies.

Abbreviation: CLL, chronic lymphocytic leukemia.

Table 2 Comparison of commercially available anti-CD20 antibodies

Antibody	Obinutuzumab	Rituximab	Ofatumumab
Trade name (EU)	Gazyvaro	MabThera	Arzerra
Manufacturer	Roche	Roche	GlaxoSmithKline
Antibody type	II	I	I
IgG subclass	IgG1	IgG1	IgG1
Structure	Humanized	Chimeric	Fully human
Binding to CD20 epitope	Large loop	Large loop	Large and small loop
Binding to lipid rafts	−	++	++++
ADCC	++++	++	++
CDC	+	++	++++
Direct cell death induction	++++	+	+

Abbreviations: ADCC, antibody-dependent cellular cytotoxicity; CDC, complement-dependent cytotoxicity; l Ig, immunoglobulin.

Table 3 Comparison of patient characteristics, efficacy, and toxicity of anti-CD20 antibody–chlorambucil combinations from CLL11 study

	R–CLB	G–CLB	P-value
n	233	238	ns
Median age, years	73	74	ns
Males, %	64	59	ns
Binet stage C, %	36	36	ns
Median CIRS score	8	8	ns
Median creatinine clearance, mL/min	61	61	ns
Unmutated IGHV, %	62	61	ns
FISH del 11q/17 p, %	19/5	16/8	ns
B2M >3.5 mg/L, %	35	32	ns
Median cycles administered	6	6	ns
ORR%	65	78	<0.001
CR%	7	21	<0.001
MRD negativity in peripheral blood, %	3	38	<0.001
Median PFS, months	15.2	26.7	<0.001
Grade III/IV infusion-related reactions, %	4	20	NR
Grade III/IV neutropenia, %	28	33	NR
Grade III–V infections, %	14	12	ns

Abbreviations: ORR, overall response rate; CR, complete response; CLB, chlorambucil; G, obinutuzumab; R, rituximab; B2M, β2-microglobulin; IGHV, immunoglobulin heavy chain variable region; FISH, fluorescent in situ hybridization; MRD, minimal residual disease; ns, not significant (P>0.01); NR, not reported; PFS, progression-free survival; CIRS, Cumulative Illness Rating Scale.