In a pooled analysis of two parallel single-center phase I/II studies reported in the Journal of Clinical Oncology, Ramos et al found that anti-CD30 chimeric antigen receptor (CAR) T-cell therapy produced responses in a high proportion of patients with relapsed or refractory Hodgkin lymphoma.

As stated by the investigators, “CAR T-cell therapy of B-cell malignancies has proved to be effective. We show how the same approach of CAR T cells specific for CD30 can be used to treat Hodgkin lymphoma.”

Study Details

In the studies, 28 patients with relapsed or refractory disease were enrolled at University of North Carolina, Chapel Hill, between September 2016 and December 2019, and 28 patients were enrolled at Baylor College of Medicine between June 2017 and November 2019. Of these, 25 and 17 patients, respectively, received CD30-specific CAR T-cell therapy after lymphodepletion with bendamustine alone, bendamustine and fludarabine, or cyclophosphamide and fludarabine. Treated patients had received a median of seven prior lines of therapy (range = 2­–23) with agents including brentuximab vedotin, checkpoint inhibitors, and autologous or allogeneic stem cell transplantation.

Responses

Among 37 patients evaluable for response, objective response was observed in 23 (62%), including complete response in 19 (51%). An additional four patients (11%) had stable disease. According to lymphodepletion regimen, objective responses were observed in 0 of 5 patients receiving bendamustine alone, 12 (80%) of 15 patients receiving bendamustine/fludarabine, and 11 (65%) of 17 patients receiving cyclophosphamide/fludarabine. Thus, objective response was observed in 23 (72%) of 32 patients receiving fludarabine-based lymphodepletion, including complete response in 19 (59%). 

After median follow-up of 533 days, 1-year progression-free survival and overall survival among all evaluable patients was 36% (95% confidence interval [CI] =21%–51%) and 94% (95% CI = 79%–99%), respectively. 

Toxicities

There were no dose-limiting toxicities associated with CD30-specific CAR T-cell infusions in either study. Among the 42 patients who received treatment, the most common grade ≥ 3 adverse events were lymphopenia (100%), leukopenia (57%), neutropenia (48%), rash (48%), and thrombocytopenia (26%). Cytokine release syndrome—all grade 1—occurred in 24% of patients. No neurologic toxicities were observed.

The investigators concluded, “Heavily pretreated patients with relapsed or refractory Hodgkin lymphoma who received fludarabine-based lymphodepletion followed by CD30-specific CAR T cells had a high rate of durable responses with an excellent safety profile, highlighting the feasibility of extending CAR T-cell therapies beyond canonical B-cell malignancies.”

Barbara Savoldo, MD, PhD, of Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Institutes of Health, National Cancer Institute, and Leukemia & Lymphoma Society. For full disclosures of the study authors, visit ascopubs.org.