CAR-T for Pediatric Diffuse Large B-Cell Lymphoma Type Post-Transplant Lymphoproliferative Disorder in a Post Heart Transplant Patient

Introduction Diffuse Large B-cell Lymphoma (DLBCL) type post-transplant lymphoproliferative disorder (PTLD) is a common complication in patients receiving immune suppression post solid organ or bone marrow transplant. Treatments for PTLD include: reduction of immunosuppression, CD20 monoclonal antibody therapy, chemotherapy, radiation, or a combination of modalities. Tisagenlecleucel (a CD-19 directed chimeric antigen receptor T-cell) is approved for treatment of refractory DLBCL, but is rarely used as treatment for PTLD. Objective Describe an experience of tisagenlecleucel use for refractory DLBCL post orthotopic heart transplant Methods Case description Results A 20-year-old male with a history of orthotopic heart transplant developed a left cervical mass at 17 years of age. A biopsy revealed DLBCL. Staged rituximab was utilized as initial treatment. Due to refractory disease, he received rituximab, cyclophosphamide, and prednisone. Peripheral blood mononuclear cell harvest was performed and sent for manufacturing. He continued tacrolimus throughout harvest. Harvest procedure was successful with one day of standard MNC collection. Etoposide, doxorubicin, vincristine, prednisone, and cyclophosphamide were given followed by targeted radiation. He underwent surgical resection of the neck mass due to refractory disease. Post-resection PET exhibited refractory disease.During CAR-T therapy, he was admitted to the pediatric intensive care unit for monitoring of heart function due to risk for cytokine release syndrome (CRS) and tumor lysis syndrome. A multidisciplinary team participated in daily rounds. He underwent lymphodepletion with fludarabine and cyclophosphamide before receiving tisagenlecleucel. The patient developed grade 2 CRS on day +1 and Tocilizumab was initiated. He progressed to grade 3 CRS on day +2 and 1 dose of Decadron was given along with vasopressor support. Symptoms improved and Tocilizumab was discontinued on day +3. He was maintained on immunosuppressive therapy with Tacrolimus throughout the admission. The patient discharged on day +10 and had no additional evidence of CRS or ICANS. Day +30 PET scan revealed partial response, and day +77 PET scan exhibited progressive disease. The patient maintains persistent B-cell aplasia. Discussion Tisagenlecleucel is a viable treatment option for treatment of refractory DLBCL in post organ transplant patients with manageable toxicities. Harvest of peripheral blood stem cells is well-tolerated without compromising the transplanted organ. Adverse effects of tisagenlecleucel in a post-heart transplant patient are similar to cancer patients. Optimal patient outcomes may be achieved through multi-disciplinary management. Effectiveness of CAR-T cell therapy for solid tumors continues to be less than ideal, and further research is needed to optimize CAR-T therapy in tumor microenvironments.