Novel targets in aggressive lymphoma.

Targeting CD20 with the monoclonal antibody rituximab has improved survival in patients with aggressive B-cell lymphomas, the majority of which are cured with chemoimmunotherapy. Patients progressing through or relapsing after their treatment have a poor prognosis. Despite a number of promising novel agents with efficacy in relapsed disease, randomized trials building on the chemoimmunotherapy backbone have failed to show further survival benefit. Significant progress has been made in the last few years in relapsed or refractory disease with the emergence of therapies that harness the patient's immune system to fight disease. The approval of 2 chimeric antigen receptor T-cell products has provided potential for curative therapy, although challenges remain with toxicities and access. The approval of the antibody drug conjugate polatuzumab in combination with chemoimmunotherapy has offered survival benefit to patients who are not candidates for more aggressive approaches and has the potential to change the standard of care for initial management. Several targeted agents have proven effective, but the majority do not produce durable responses, requiring development in combination with other targeted or conventional therapies. Herein, promising targets in aggressive lymphoma with the greatest potential for improving outcomes in these patients are discussed. Novel therapies, their toxicities, and their potential role in initial or subsequent treatment are highlighted.