Transient responses and significant toxicities of anti-CD30 CAR T cells for CD30+ lymphomas: results of a phase I trial.

New treatments are needed for relapsed and refractory CD30-expressing lymphomas. We developed a novel anti-CD30 CAR, designated 5F11-28Z. Safety and feasibility of 5F11-28Z-transduced T cells (5F11-T) were evaluated in a phase I dose escalation clinical trial. Patients with CD30-expressing lymphomas received 300 mg/m2 or 500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine on days -5 to -3 followed by infusion of 5F11-T on day 0. Twenty-one patients received 5F11-T infusions. Twenty patients had Classical Hodgkin lymphoma, and 1 had anaplastic large cell lymphoma. Patients were heavily pretreated, with a median of 7 prior lines of therapy and substantial tumor burden, with a median metabolic tumor volume (MTV) of 66.1 mL (range 6.4 - 486.7 mL). The overall response rate was 43%; one patient achieved a complete remission. Median event-free survival was 13 weeks. Eleven patients had cytokine release syndrome (CRS; 52%). One patient had grade 3 CRS, and there was no grade 4-5 CRS. Neurologic toxicity was minimal. Nine patients (43%) had new onset rashes. Two patients (9.5%) received extended courses of corticosteroids for prolonged severe rashes. Five patients (24%) had grade 3-4 cytopenias with recovery time of 30 days or more, and 2 of these patients (9.5%) had prolonged cytopenias with courses complicated by life-threatening sepsis. The trial was halted early due to toxicity. Median peak blood CAR+ cells/µL was 26 (range 1-513), but no infiltration of CAR+ cells was detected in lymph node biopsies. 5F11-T had low efficacy and substantial toxicities, which limit further development of 5F11-T. CT# NCT03049449.