When treating patients with relapsed disease, it is helpful to distinguish between those who will definitely not be eligible for CAR T-cell therapy vs those for whom CAR T-cell therapy might be a possibility. It is also important to distinguish between bridging therapy and debulking therapy. 

When a patient has R/R DLBCL, their eligibility for CAR T-cell therapy is determined by a number of factors, including the individual’s recurrent disease burden, performance status, disease kinetics, and symptom burden. For those with too much disease or who are too sick from their lymphoma, debulking therapy is required. For these patients, the goal of debulking therapy is to produce a response and to improve their performance status and other parameters so that they might then be considered for CAR T-cell therapy. 

When we speak of bridging therapy, it is in the context of patients who have R/R DLBCL and are candidates for CAR T-cell therapy. Such individuals may have already been evaluated and deemed fit for CAR T-cell therapy, but there is additional time needed for them to undergo apheresis, and the process of cellular generation takes time as well. During this period, which typically lasts for weeks, patients with rapidly progressive disease may require intervening therapy to hold their disease at bay. In this situation, we try to control the disease with bridging therapy until the CAR T cells become available. As we are simply controlling the disease until the patient can be infused with CAR T cells, there is typically no response evaluation, scanning, or restaging after bridging therapy.

Because of these differences, treatments that may be appropriate for debulking may not be appropriate for bridging to CAR T-cell therapy, and vice versa. Bridging therapy should be given in such a way that it does not preclude the administration of CAR T-cell therapy or interfere with its effectiveness. 

Some of the therapies that are available for the treatment of R/R DLBCL target CD19, which is also the target of commercially available CAR T cells. Since therapies such as tafasitamab or loncastuximab tesirine target CD19, there is a theoretical concern that their use as bridging therapies prior to the administration of CAR T-cell therapy could interfere with the efficacy of the latter. Thus, in the absence of data showing that this is not the case, many of us gravitate toward bridging therapies that are effective against the lymphoma but do not target CD19. These include polatuzumab vedotin plus bendamustine and rituximab, simple chemoimmunotherapy, or even radiation to isolated sites of progressive disease. 

One could also consider Bruton tyrosine kinase inhibitors or immunomodulatory imide drugs for bridging. We know that Bruton tyrosine kinase inhibitors have a reasonable response rate in patients with R/R nongerminal center DLBCL; responses tend to be brief, but that is acceptable with bridging therapy.