Developing anti-CD19 antibody-based combinations in lymphoma

Tafasitamab (MOR208, previously XmAb5574) is an antibody that is Fc-enhanced through two amino acid modifications within the Fc region, and has direct cytotoxic effects and additional antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.5,6 Monotherapy with tafasitamab in B-cell lymphomas showed acceptable activity, with objective response rates of 26% in diffuse large B-cell lymphoma and 29% in follicular lymphoma.7 In The Lancet Oncology, Gilles Salles and colleagues8 report the results of a phase 2 trial (L-MIND) that builds on the encouraging results reported with tafasitamab monotherapy. Recent trials in diffuse large B-cell lymphoma have led to the approval of treatments such as CAR T-cell therapy as outlined above, as well as the anti-CD79b-targeted antibody–drug conjugate polatuzumab vedotin, given in combination with bendamustine and rituximab.9 Clinicians and investigators face the challenge of doing appropriate clinical trials to identify the true benefit of these novel drugs and regimens in patients with diffuse large B-cell lymphoma. CAR T-cell therapy offers the opportunity for long-term disease control and potential cure, and thus is viewed as the new standard of care (where available) for eligible patients with relapsed and refractory diffuse large B-cell lymphoma after two lines of systemic therapy. Because tafasitamab targets CD19, crucial questions will include the effect of the antibody on CD19 expression at relapse (and the potential implications for CAR T-cell therapy if tumours have antigen loss or loss of antigen density) and the activity of tafasitamab-based approaches in patients with disease progression after anti-CD19 CAR T-cell therapy in whom the target antigen density might be low.