Dr Danilov on Sequencing CAR T-Cell Therapy and Bispecific Antibodies in DLBCL

"In terms of sequencing, there is now an emerging question of whether we should be using bispecifics or CAR T-cells first. Some of this will be driven by logistical issues; some will be driven by whether there is easy accessibility to a tertiary care center that can [administer] CAR T-cell therapy; and some will be driven by patient comorbidities, cost, and other factors."

Alexey Danilov, MD, PhD, the Marianne and Gerhard Pinkus Professor of Early Clinical Therapeutics at City of Hope and co-director of the Toni Stephenson Lymphoma Center, outlined key considerations and remaining questions surrounding treatment sequencing for patients with diffuse large B-cell lymphoma (DLBCL).

Notably, Danilov's insights followed the publication of a consensus manuscript examining therapeutic developments and unmet needs in mantle cell lymphoma (MCL), DLBCL, and chronic lymphocytic leukemia (CLL).

According to Danilov, the availability of multiple highly active therapies—including CAR T-cell therapies, bispecific antibodies, and CD19-directed agents—has introduced complexity into treatment sequencing for patients with relapsed/refractory DLBCL. A central question is whether bispecific antibodies should be utilized before CAR T-cell therapy or vice versa. He emphasized that sequencing decisions will likely be influenced by several factors, including logistical constraints related to CAR T-cell therapy administration, proximity to specialized treatment centers, patient comorbidities, and cost considerations.

Emerging data suggest bidirectional efficacy between these modalities. Bispecific antibodies, which predominantly target CD20, appear to retain activity following disease progression on CAR T-cell therapy. Conversely, some patients with DLBCL who experience disease progression on bispecific antibodies may still respond to CAR T-cell therapy, contingent upon continued antigen expression. This has important implications for sequencing decisions, particularly as bispecific antibodies become more integrated into earlier lines of therapy.

Danilov noted that CAR T-cell therapies have already displaced autologous stem cell transplantation in certain clinical scenarios, such as in patients with primary refractory disease or those who relapse within 12 months of frontline chemoimmunotherapy. However, in later lines of therapy, data are accumulating in support of both CAR T-cell therapy and bispecific antibodies. As a result, optimal sequencing remains undefined, and future comparative and real-world evidence will be critical in shaping the standard of care.