Ofatumumab: a novel monoclonal anti-CD20 antibody

Figures & data

Table 1 Preclinical characteristics of ofatumumab

Ofatumumab is a type I antibody (lipid rafts)

Epitope on CD20 is distinct from rituximab’s epitope

Epitope encompasses both the small and large loops of CD20

Ofatumumab binds CD20 more tightly with slower off-rate

Ofatumumab induces complement-dependent cytotoxicity (CDC)

Ofatumumab induces antibody-dependent cytotoxicity (ADCC)

Ofatumumab caused prolonged B-cell depletion in animal studies

Table 2 Clinical studies of weekly single-agent ofatumumab

Phase	N	Disease	Dosing schedule	Response rate	Median PFS
I/II	27^a	CLL (relapsed)	500 mg week 1	48%	Not reported
			2000 mg weeks 2–4
II	59	CLL (FA-REF)	300 mg week 1	58%	5.7 months
	79	CLL (BFR)	2000 mg weeks 2–8	47%	5.9 months
			2000 mg monthly × 4
I/II	38^b	FL (relapsed)	300–1000 mg weeks 1–4	43%	8.8 months
II	116	FL (refractory)	300 mg week 1	11%	6.0 months
			500–1000 mg weeks 2–8

a Patients in cohort 3;

b Patients who were evaluable for response.

Abbreviations: N, number of patients; PFS, progression-free survival; CLL, chronic lymphocytic leukemia; FA-REF, fludarabine and alemtuzumab refractory; BFR, bulky fludarabine refractory; FL, follicular lymphoma.

Table 3 Potential role of pharmacogenomics in ofatumumab

Antibody-dependent cellular cytotoxicity (ADCC)

FCGR3a polymorphisms

158 V/V (high affinity)

158 F/F (low affinity)

158 V/F (intermediate affinity)

Complement-dependent cytotoxicity (CDC)

CD55 and CD59

High expression (resistant to CDC)

Low expression (sensitive to CDC)

Exposure to drug–drug clearance

Increased metabolism of antibody (lower exposure/activity)

Increased antibody clearance (lower exposure/activity)