Evolving Paradigms: CAR-T Eligibility, Barriers, and Implementation in R/R LBCL

Primary refractory diffuse large B-cell lymphoma has historically been a difficult disease to treat, with limited options offering only modest curative potential. In the past, second-line treatment typically involved additional chemotherapy followed by autologous stem cell transplant—an approach that achieved cure in only a small fraction of patients. However, the treatment landscape has changed significantly with the advent of cellular therapies. Recent randomized clinical trials have shown clear benefits of chimeric antigen receptor (CAR) T-cell therapy over traditional transplant-based approaches in the second-line setting, providing renewed hope for long-term disease control in patients with early relapsed or refractory disease.

Despite these advancements, determining eligibility for CAR T therapy remains a critical and sometimes misunderstood step. Guidelines recommend CAR T in the second-line setting for eligible patients, but the lack of standardized criteria for eligibility assessment can be problematic, especially in community settings. Community oncologists may make early judgments based on limited familiarity with transplant or cellular therapies, which can inadvertently prevent patients from receiving curative treatment. It is crucial that patients be referred promptly to specialized CAR T centers where thorough eligibility assessments can be made. True ineligibility due to factors like severe organ dysfunction or poor cardiac function is rare, and many patients can still proceed with CAR T with supportive care measures in place.

Nonclinical barriers such as geographic access, the need for a caregiver, and financial or insurance hurdles also pose challenges to timely CAR T initiation. Many patients must travel to and temporarily reside near treatment centers, often with a caregiver. To address these logistical concerns, holding or bridging therapies can stabilize disease while social workers help patients coordinate housing, transportation, and insurance approvals. Though these barriers can delay treatment, a coordinated multidisciplinary effort ensures that patients are not excluded from lifesaving therapy due to manageable nonmedical factors.