Evolving Paradigms: A Review of Approved Bispecific Antibodies for R/R LBCL

Bispecific antibodies have rapidly become an important addition to the treatment options available for certain lymphomas. Following their initial approvals as single agents in the third-line setting, these therapies are now being explored in combinations for earlier lines of treatment, including frontline and second-line settings. They offer a valuable alternative for patients who relapse after CAR T-cell therapy—a group for whom treatment choices become increasingly limited. Bispecifics have demonstrated promising efficacy in pivotal trials, showing good outcomes even in patients previously treated with CAR T, and they tend to have a different, often more manageable, toxicity profile compared with traditional chemotherapy.

These agents often cause hematologic adverse effects, but unlike chemotherapy, patients are more likely to tolerate bispecific monotherapy, making them suitable for individuals who might not withstand more intensive treatments. In some cases, bispecifics are even used before CAR T-cell therapy, especially for patients whose disease is progressing rapidly or whose overall condition precludes immediate CAR T eligibility. By controlling the disease temporarily with a bispecific, these patients may become eligible for CAR T at a later time. Despite this, many centers still prioritize CAR T-cell therapy for eligible patients in the second and third-line settings, reserving bispecifics for those who cannot undergo CAR T.

Safety considerations with bispecific antibodies show that while they can cause toxicities similar to those seen with CAR T-cell therapies, such as cytokine release syndrome and neurotoxicity, the frequency and severity of these events are generally lower. The reduced risk of high-grade toxicities allows for more flexibility in patient treatment, often enabling treatment initiation in specialized centers followed by ongoing monitoring and care in the community setting. This approach improves patient quality of life by reducing the need for prolonged hospital stays while ensuring careful follow-up during therapy administration.