Persistent Cytopenias after Chimeric Antigen Receptor T-Cell Immunotherapy for CD19+ Aggressive Lymphoma: A Single Institution Experience

Abstract

Background Chimeric antigen receptor (CAR) T cell therapy is FDA-approved for the treatment of refractory or multiple-relapsed CD19+ B-NHL. Despite its ability to induce rapid and durable responses, it carries the risk of significant toxicities including cytokine release syndrome (CRS) and reversible encephalopathy. There have been reports of bone marrow failure after engineered-T cell receptor cellular immunotherapy, however, no such reports exist for CAR-T cells. Here, we report persistent cytopenias after T cell therapy (PCTT) following axicabtagene ciloleucel (axi-cel) infusion. Methods A retrospective analysis of all patients who were treated with commercial axi-cel at the University of Miami/Sylvester Cancer Center was conducted through 10/12/18. PCTT was defined as patients who were alive at 30 days after axi-cel infusion and did not have ANC>500cells/mL without growth factor support. Results Fifteen patients with CD19+ relapse or refractory B-NHL were identified who received commercial axi-cel, but of those 15 patients, 13 were evaluable (one died from cerebral edema on day +7 and the other has not reached the day +30 benchmark yet). Six of the 13 evaluable patients (46%) fulfilled the criterion for PCTT. None of the 6 patients recovered ANC by day +42. Platelets of 50,000/mL or less on the first day of lymphodepleting chemotherapy was found to be a significant predictor for PCTT (p=0.01) in 5 of 6 PCTT patients. We did not find any other predictive associations with factors such as bulky disease, CRP, ferritin, LDH, ANC, or hemoglobin. It was observed that 4 of 6 (66.7%) patients with PCTT developed CRS of at least grade 2 the day after CAR-T infusion requiring tocilizumab infusion as opposed to only 1 of 7 (14.3%) who did not develop PCTT. Conclusions Low platelet count at the first day of lymphodepleting chemotherapy may be an indicator of low stem cell reserve and a predictor for PCTT after axi-cel. In addition, early onset of at least grade 2 CRS may contribute to PCTT after axi-cel. Notably, 5 of 6 patients who went on to develop PCTT would have been excluded from participation in the ZUMA-1 registration trial.