Top advances in lymphoma for 2021.

Chimeric antigen receptor (CAR) T-cell therapy, antibody-drug conjugates, bispecific T-cell redirectors, and agents targeting tonic B-cell receptor signaling have altered the paradigm for three of the most common lymphomas in the year 2021. For diffuse large B-cell lymphoma, the POLARIX study has shown improvement on the standard backbone of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in the frontline setting, a feat that had not been achieved despite great efforts over the past 20 years. In the relapsed and refractory setting, two unique CAR T-cell products have displaced autologous transplantation to the third line, and they allow patients with chemotherapy-resistant disease to receive approved therapy earlier. CAR T-cell products, once used exclusively in the aggressive lymphoma arena, are now showing high response rates and durable activity against indolent lymphomas. The investigation of mosunetuzumab in indolent lymphomas offers another option for patients who have received multiple lines of cytotoxic drugs. On the basis of these trends, PI3K inhibitors are being displaced in favor of safer and more durable constructs. In addition, within the past year, the approval and implementation of zanubrutinib for marginal zone lymphoma have filled a need for later line therapy, especially for less fit and elderly patients.