Development and Integration of Antibody-Drug Conjugate in Non-Hodgkin Lymphoma

Rituximab, a monoclonal antibody (MAb) against CD20, was the first MAb approved by the US Food and Drug Administration (FDA) for treatment of B cell non-Hodgkin lymphoma (B-NHL). Conjugating toxins to MAb was a technical challenge; however, with improvements in linker technology, immunoconjugates were constructed and revolutionized cancer treatment. Gemtuzumab ozogamicin was the first antibody drug conjugate (ADC) approved by the FDA. Because of the success of brentuximab vedotin and ado-trastuzumab emtansine in treating Hodgkin lymphoma (HL) and HER2-positive breast cancer, respectively, newer ADCs are being investigated. Brentuximab vedotin is approved for both HL and anaplastic large cell lymphoma. Newer ADCs, such as polatuzumab vedotin (targeting CD79b), pinatuzumab vedotin (targeting CD22), inotuzumab ozogamicin (targeting CD19), SAR3419 (targeting CD19), IMGN529 (targeting CD37), and SGN-CD19A (targeting CD19), have shown promising preclinical and early clinical activity. These findings will change the landscape of B-NHL treatment away from age-old "CHOP"-based chemotherapies.