There have been several recent developments in the treatment of B-cell lymphoma; however, one of the most significant advances has been the development of chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy is a type of personalized immunotherapy that can help cure some people with aggressive non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), the most common form of aggressive NHL . CAR T-cell therapy has revolutionized the treatment of hematologic malignancies over the past 5 years, with impressive response rates and durable remissions for patients who previously had no viable options. This strategy is highly effective in patients with relapsed/refractory DLBCL, as well as mantle cell lymphoma, follicular lymphoma, acute lymphoblastic leukemia (ALL), and multiple myeloma, as evidenced by recent regulatory approvals .
In 2021, the FDA also approved lisocabtagene maraleucel (liso-cel), a new CAR T-cell therapy for the treatment of adults with relapsed or refractory (nonresponsive) large B-cell lymphoma (LBCL) have been treated with at least 2 prior lines of therapy. These products have design differences, including differences in the costimulatory domain, mechanism of gene/transgene delivery, ability for cryopreservation, and need for T-cell selection.
The CAR T-cell therapy axi-cel demonstrated superior results in the ZUMA-7 clinical trial, which compared CAR T-cell therapy directly to traditional chemotherapy with intended autologous stem cell transplant (ASCT). About 55% of patients were still alive 4 years after receiving axi-cel, compared with 46% of those who initially received the standard treatment for relapsed disease. Based on these results, axi-cel is now the preferred treatment for people whose DLBCL has recurred with 12 months of front-line treatment or who are resistant to standard initial treatment.
Additionally, the BELINDA trial was a randomized phase 3 trial that compared CAR T-cell therapy with liso-cel with second-line chemotherapy with planned ASCT. Like ZUMA-7, this study also demonstrated an improvement in progression-free survival (PFS) compared to standard treatment. As such, CAR T-cell therapy represents the new standard of care for second-line treatment in appropriate patients with refractory or early relapsing LBCL.
There have been several other recent studies on the use of CAR T-cell therapy for B-cell lymphoma. One study, published in Blood Advances (2023), found that receiving a greater number of therapies prior to CAR T-cell therapy is associated with poorer outcomes in patients with aggressive relapsed/refractory B-cell NHL. The study, which included 514 patients from 13 centers treated with CAR-T for aggressive B-cell NHL between 2015 and 2021, found that a greater number of lines of therapy before CAR-T apheresis and bridging therapy were predictive of inferior PFS and overall survival.
Another study compared 2 CD19-targeting CAR T-cell treatments, axi-cel and tisa-cel, with ASCT in the second line setting for LBCL. The study found that axi-cel was superior to ASCT, with longer median event-free survival and a higher response rate. However, tisa-cel was not found to be superior to ASCT . Further studies will be needed to definitively characterize the relative benefits of CAR-T cell therapies and standard second-line treatments for different subgroups of patients with LBCL.