Optimizing Real-World Outcomes in High-Risk Relapsed/Refractory (r/r) DLBCL with CAR T Cell Therapy: A Vodcast and Case Example.

Chimeric antigen receptor (CAR) T-cell therapy is effective in the treatment of patients with diffuse large B cell lymphoma (DLBCL), even those with high-grade disease. However, it has a unique safety profile, including cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and robust management of these events are important to maximize benefits. The aim of this vodcast is to outline the management of a patient receiving CAR T-cell therapy for relapsed/refractory (r/r) DLBCL. In January 2005, the patient was diagnosed with atypical chronic lymphocytic leukemia (CLL) and treated with two cycles of fludarabine and cyclophosphamide before stopping due to skin toxicity. In 2007, the patient progressed and received alemtuzumab. In January 2018, the patient was diagnosed with DLBCL (nongerminal center, stage IV-A, bone marrow infiltration); a clonality analysis with the previous CLL provided a negative result. In March 2018, the patient received first-line treatment with rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP)) for six cycles. At this point, a positron emission tomography (PET) scan showed complete remission. Unfortunately, in December 2018, they experienced a relapse and second-line therapy with rituximab, etoposide, cytarabine, cisplatin, and prednisone (R-ESHAP) was started. Following the second cycle of R-ESHAP in February 2019, the patient progressed, and third-line treatment was provided by rituximab plus ifosfamide, gemcitabine, vinorelbine, and prednisone (R-IGEV) for four cycles. The last cycle of R-IGEV was received in May 2019, but the patient progressed. In July 2019, the patient received a tisagenlecleucel infusion. The authors describe the effectiveness of the CAR T-cell therapy and how the adverse events (AEs) encountered, including CRS and ICANS, were managed. Results from real-world evidence studies of tisagenlecleucel in DLBCL are similar to those observed in the pivotal clinical trials. In conclusion, CAR T-cell therapy can be effective and achieve long-lasting, durable responses in patients with high-risk r/r DLBCL. However, long-term follow up is key to watch out for late AEs and potential lymphoma relapse.