Lori A. Leslie, MD, assistant professor, Hackensack Meridian School of Medicine, director, Indolent Lymphoma and Chronic Lymphocytic Leukemia Research Programs, John Theurer Cancer Center, and Andre H. Goy, MD, Hackensack Meridian Chief Medical Officer Health Oncology Care Transformation Services, President and Chief Medical Officer of John Theurer Cancer Center at Hackensack University Medical Center, and Lymphoma Division Chief at John Theurer Cancer Center, share strategies when CAR T-cell therapy is not an option .
The population of patients ineligible for CAR T-cell therapy is shrinking due to improved toxicity management and intervention, Leslie says. Now, referring providers may be surprised which patients are eligible for CAR T-cell therapy. As such, it is important to evaluate patients at a CAR T-cell therapy center. However, for patients who are not eligible for CAR T-cell therapy, more options have become available. For example, in diffuse large B-cell lymphoma, agents such as tafasitamab-cxix (Monjuvi), selinexor (Xpovio), and loncastuximab tesirine-lpyl (Zynlonta) are approved for use. Currently, these agents are not curative, although they have shown high response rates, Goy says.
For patients eligible for both CAR T-cell therapy and new agents, treatment is usually sequenced so that new agents are used after CAR T-cell therapy fails, Leslie says. However, regimens that incorporate new agents into the initial therapy are also being explored. For example, the phase 3 POLARIX trial (NCT03274492) evaluated the addition of the antibody-drug conjugate polatuzumab vedotin-piiq (Polivy) to rituximab (Rituxan), cyclophosphamide, doxorubicin and prednisone. These agents are also being incorporated into existing treatment regimens as a gateway to CAR T-cell therapy, Leslie says.
In terms of experimental therapeutics, bispecific T-cell engagers have generated considerable excitement and shown encouraging responses after CAR T-cell therapy, says Leslie. However, because these agents are more easily administered than CAR T cell therapy, a key question is whether these agents will replace CAR T cell therapy in certain scenarios, Leslie concludes.