Brentuximab Vedotin and Crizotinib in Anaplastic Large-Cell Lymphoma

Abstract

Systemic anaplastic large-cell lymphoma (ALCL) is a rare, mature T-cell non-Hodgkin lymphoma. Anaplastic large-cell lymphoma cells express the surface antigen CD30, and more than half express the anaplastic lymphoma kinase (ALK) protein. These 2 proteins provide unique therapeutic targets in ALCL. Remission rates in ALCL with combination chemotherapy are approximately 80%, but relapse after first-line therapy is common. Brentuximab vedotin is a US Food and Drug Administration-approved, antibody-drug conjugate that combines an anti-CD30 antibody with monomethylauristatin E, a potent antimicrotubule agent. Response rates to brentuximab vedotin in patients with relapsed/refractory ALK and ALK ALCL have exceeded 80% with frequent complete responses and a median duration of response greater than 1 year. Brentuximab vedotin in combination with chemotherapy is being explored as a first-line therapy in ALCL. Crizotinib is an inhibitor of ALK tyrosine kinase that has been approved for the treatment of ALK non-small cell lung cancer. Successful treatment of ALK ALCL with crizotinib has been reported in pediatric patients and small case series leading to ongoing trials in relapsed/refractory ALCL. Brentuximab vedotin and crizotinib represent major advances in the treatment of ALK and ALK ALCL and will likely result in marked improvement in prognosis for this subset of aggressive lymphomas.