How to Sequence Therapies in Diffuse Large B-Cell Lymphoma Post-CAR-T Cell Failure

Opinion statement Post CAR-T failures represent a new unmet need in R/R LBCL. The prognosis is usually very poor and standard treatment options that can guide clinicians are, unfortunately, not available. While polatuzumab, tafasitamab, selinexor, and loncastuximab tesirine are available as SOC since they are FDA approved, data is lacking in the post CAR-T setting. However, they could be used in the absence of other treatment options (clinical trials). A selected group of patients may be treated with checkpoint inhibitors, likely low tumor burden or low proliferative lymphomas or those with PD-L1 expression. For localized relapses, radiation therapy could be considered. A main consideration should be given to clinical trials. So far, it appears that bi-specific antibodies have the best encouraging data (high response rates) with manageable toxicities and logistics; thus, we recommend clinicians to enroll patients in clinical trials utilizing these agents. Other cell therapies (such as dual CAR-T or allogeneic products) should also be considered; however, challenges with logistics and further immunosuppression (especially if patients had prolonged cytopenias from prior CAR-T therapy) may affect its applicability right after CAR-T relapse. It is unclear whether these options will lead to long-term remissions; thus, consolidation with stem cell transplantation (either auto or allogeneic SCT) could be considered in eligible patients.

Automated summary

Post CAR-T failures in R/R LBCL present a new unmet need with very poor prognosis. Standard treatment options are lacking, although FDA-approved medications like polatuzumab, tafasitamab, selinexor, and loncastuximab tesirine are available, data in this setting is limited. Clinical trials with bi-specific antibodies show encouraging results with manageable toxicities, suggesting their potential in this scenario. Additional cell therapies like dual CAR-T or allogeneic products may also be considered, but challenges with logistics and further immunosuppression need to be addressed. Consolidation with stem cell transplantation could be an option for eligible patients.