CAR-T Access Barriers and CNS Prophylaxis for Treating DLBCL

Dr. Graff addresses the persistent gap between the CAR-T evidence base and real-world utilization. Despite ZUMA-7 and TRANSFORM demonstrating event-free survival and overall survival superiority for anti-CD19 CAR-T over platinum chemotherapy plus autologous transplant in early relapsing and primary refractory patients, many eligible patients still don't receive it. Barriers include patient reluctance to travel, caregiver responsibilities (including farming communities unable to interrupt livelihoods), inadequate community oncologist awareness about appropriate referral timing, manufacturing and cell collection logistics, and payer reimbursement complexities.

She advocates for early bidirectional referral relationships: community oncologists calling academic lymphoma centers for guidance rather than assuming full patient transfer is required, with shared management models where CAR-T is delivered at a specialized center and subsequent monitoring returns to the primary oncologist.

Dr. Lunning notes that post-CAR-T monitoring requirements have been meaningfully streamlined based on accumulating safety data: mandatory proximity to authorized treatment centers has been reduced from 28 to 14 days, and driving restrictions reduced from 8 weeks to 2 weeks, reflecting that clinically significant events cluster in the first 14 days post-infusion. Community oncologists can manage subsequent cytopenia monitoring, blood transfusions, and other complications, allowing genuine shared care.

Dr. Johnson addresses CNS prophylaxis strategies, noting he has progressively reduced prophylaxis use as retrospective data consistently show intrathecal therapy is ineffective. He retains CNS-directed prophylaxis for double-hit lymphoma (given biological overlap with Burkitt lymphoma where CNS prophylaxis has established benefit), intravascular large B-cell lymphoma (extraordinarily high CNS involvement risk), and testicular DLBCL (where late CNS relapses are documented and high-dose intravenous methotrexate prophylaxis is used). He notes that lenalidomide's CNS penetration is a biologically interesting feature of frontMIND-based regimens that may reduce CNS relapse rates, and he looks forward to seeing CNS relapse data from that trial.