Phase I study of anti-CD30 CAR T cells for CD30+ lymphomas
Brudno JN, Natrakul DA, Karrs JX, et al. Transient Responses and Significant Toxicities of Anti-CD30 CAR T Cells for CD30+ Lymphomas. Blood Advances. 2023; (doi: 10.1182/bloodadvances.2023011470).
A promising chimeric antigen receptor (CAR) construct designed to combat CD30-positive lymphoma demonstrated low efficacy and significant toxicity in clinical study, limiting its value as a possible treatment pathway. The Phase I dose escalation trial included 21 patients with Classical Hodgkin lymphoma and 1 patient with anaplastic large cell lymphoma, each with substantial tumor burden. All participants had tried multiple previous lines of therapy — seven, on average. For this study, they received cyclophosphamide and fludarabine for 3 days, followed by a 2-day break before receiving an infusion of the novel intervention. The overall response rate to the anti-CD30 CAR (5F11-28Z) was 43%, and complete remission was documented in only one patient. The median length of event-free survival was 13 weeks. Treatment was associated with a number of adverse effects, as 11 patients developed cytokine release syndrome, 9 developed new-onset rashes, and 5 had cytopenias — prolonged with life-threatening sepsis in two cases. Researchers also reported that median peak blood CAR+ cells/µL was 26 (range 1-513), with no infiltration of CAR+ cells evident in lymph node biopsies. Based on the low efficacy and high toxicity, the trial was terminated early.