Combining Biology and Chemistry for a New Take on Chemotherapy: Antibody-Drug Conjugates in Hematologic Malignancies

Abstract

Purpose of review: This review is about the antibody-drug conjugate (ADC), a form of drug delivery consisting of a monoclonal antibody, linker, and cytotoxic payload. We summarize the history of ADC development, highlighting the three FDA-approved ADCs currently available.

Recent findings: Gemtuzumab ozogamicin is a CD33-targeted ADC linked to calicheamicin. It is approved for CD33+ AML in the first line or the relapsed or refractory (R/R) setting. Brentuximab vedotin is a CD30-targeted ADC bound to MMAE. It is approved for the treatment of certain R/R CD30+ lymphomas. Recently, it has been approved for first line therapy with chemotherapy in advanced HL. Inotuzumab ozogamicin is a CD22-directed ADC attached to calicheamicin indicated for the treatment of adults with R/R B cell precursor ALL. Three ADCs have been approved for the treatment of various hematologic malignancies. We discuss the pertinent human trials that led to FDA approval. We include our perspectives about drug resistance, toxicities, and future development.

Keywords: ADC; Antibody-drug conjugate; Brentuximab vedotin; Gemtuzumab ozogamicin; Inotuzumab ozogamicin.