Clinical Binding Properties, Internalization Kinetics, and Clinicopathologic Activity of Brentuximab Vedotin: An Antibody-Drug Conjugate for CD30-Positive Lymphoid Neoplasms

center dot Brentuximab vedotin (b-vedotin), a CD30-directed antibody-drug conjugate, has shown activity in treating CD30-positive (CD30+) neoplasms (classical Hodgkin lymphoma [CHL] and systemic anaplastic large cell lymphoma [ALCL]); however, its in vivo saturation, internalization kinetics, and pathologic findings are unknown. center dot We quantified antigen density on CD30+ cell lines cultured with b-vedotin and demonstrated the greatest expression of CD30 and bound b-vedotin at 24 to 48 hours, reaching a nadir by 120 hours. Similarly, serial tumor biopsies from a patient with relapsed ALCL revealed maximal CD30 expression (1.01x105 molecules/cell) at baseline. After treatment, CD30 (7.83x104 molecules/cell at 24 hours; 5.08x104 molecules/cell at 48 hours) and bound b-vedotin (2.26x103 molecules/cell at 24 hours and 1.40x103 molecules/cell at 48 hours) antigen density rapidly declined, consistent with internalization. Histologic evaluation showed a dense infiltrate of neoplastic CD30+ cells before treatment, apoptosis at 48 hours, and no neoplastic cells at day 21. center dot These results demonstrate the potent and rapid antitumor properties and support the mechanism of action of b-vedotin. Additionally, as relatively few b-vedotin molecules are required for clinical efficacy, these results suggest that this drug should be evaluated in neoplasms with relatively low expression of CD30.