Targeted therapy for Hodgkin lymphoma and systemic anaplastic large cell lymphoma: focus on brentuximab vedotin

Figures & data

Figure 1 Brentuximab vedotin mechanism of action.

Notes: Brentuximab vedotin is an ADC composed of a chimeric anti-CD30 antibody, covalently linked via valine-citrulline dipeptides to four MMAE molecules (on average) (1). The ADC first binds to CD30 on the target cell surface (2) and is internalized by receptor-mediated endocytosis (3 and 4). Fusion with lysosomes (5) results in the proteolytic cleavage of the dipeptide linker, yielding free MMAE in the cytoplasm. MMAE then binds tubulin (6), inhibiting tubulin polymerization, and causing growth arrest.
Abbreviations: ADC, antibody–drug conjugate; CD, cluster of differentiation; MMAE, monomethyl auristatin E.

Table 1 Clinical studies with anti-CD30 monoclonal antibodies

Drug	Phase	Disease	Patients	Response	Reference
MDX-060	I/II	HL, ALCL, CD30+ TCL	63 (HL), 7 (ALCL), 2 (CD30+ TCL)	ORR: 4 pts with HL, 2 with ALCL	Ansell et al^Citation4
SGN-30	II	HL and ALCL	38 (HL), 41 (ALCL)	ORR: 0 with HL, 17.1% with ALCL	Forero-Torres et al^Citation5
SGN-35 (q3)	I	HL and ALCL	42 (HL), 2 (ALCL), 1 (AITL)	ORR: 38%; CR: 24%	Younes et al^Citation75
SGN-35 (q1)	I	HL and ALCL	38 (HL), 5 (ALCL), 1 (PTCL)	ORR: 59%; CR: 34%	Fanale et al^Citation76
SGN-35 (q3)	II	HL	102	ORR: 75%; CR: 34%	Younes et al^Citation78
SGN-35 (q3)	II	ALCL	58	ORR: 86%; CR: 57%	Pro et al^Citation77
SGN-35	Ret	HL	45	ORR: 60%; CR: 22%	Rothe et al^Citation81
SGN-35	Ret	HL, ALCL, CD30+ TCL	18 (HL), 5 (ALCL), 1 (CD30+ TCL)	ORR: 67%; CR: 25%	Gibb et al^Citation82
SGN-35	CS	Relapsed HL after allo-SCT	25	ORR: 50%; CR: 38%	Gopal et al^Citation84

Abbreviations: AITL, angioimmunoblastic T-cell lymphoma; ALCL, anaplastic large cell lymphoma; allo-SCT, reduced-intensity stem cell transplant; CD, cluster of differentiation; CR, complete remission; CS, case series; HL, Hodgkin lymphoma; ORR, overall response rate; PTCL, peripheral T-cell lymphoma; pts, patients; q1, weekly administration; q3, administration once every 3 weeks; Ret, retrospective; TCL, T-cell lymphoma.

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