Patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) who were treated with a CAR-T cell therapy experienced durable responses with favorable safety profiles, according to 2 parallel phase 1/2 studies published in the Journal of Clinical Oncology.

The investigators conducted the phase 1/2 ATLAS ( Identifiers: NCT02690545) and phase 1 RELY-30 ( Identifier: NCT02917083) clinical trials to determine whether CAR T-cell therapy targeting CD30 could be used to treat HL.

In total, 41 patients (median age, 35 years; 67% men) with R/R HL were evaluated, 1 of whom was treated twice, with both instances included in the analysis. Patients underwent lymphodepletion before receiving anti-CD30 CAR T-cell therapy with either bendamustine alone, bendamustine and fludarabine, or cyclophosphamide and fludarabine. Safety was the primary endpoint of the analysis.

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The median number of prior therapies among patients in this analysis was 7 (range, 2-23). Among these were brentuximab vedotin (90% of patients), checkpoint inhibitors (81%), and autologous (76%) or allogeneic (24%) stem cell transplantation.

Dose-limiting toxicities reportedly did not occur on either trial. A total of 10 patients (24%) experienced cytokine release syndrome, however, all cases were grade 1. Neurotoxicity was not observed in the patient population. The most common grade 3 or higher adverse events were lymphopenia and leukopenia.

Evaluable patients (37 patients) showed an overall response rate (ORR) of 62% and a complete response (CR) rate of 51%. Stable disease and progressive disease were reported for 11% and 27% of patients, respectively. For patients who had undergone fludarabine-based lymphodepletion and who had active disease (32 patients), the ORR was 72%, with a CR rate of 59%.

The 1-year progression free survival (PFS) rate among evaluable patients in this study was 36% (95% CI, 21%-51%). PFS was significantly longer among patients treated with fludarabine-based conditioning vs bendamustine alone (P =.002). The 1-year overall survival (OS) was 94% (95% CI, 79%-99%). The type of lymphodepletion therapy used was not shown to be associated with OS.

CAR T cell peak expansion showed dose dependence overall (P =.008). CAR T persistence was also greater with a higher dosage, such as with 2 x 108 cells/m2 compared with 2 x 107 cells/m2 or 1 x 108 cells/m2 (P <.001). However, these patterns reportedly were not linked to clinical outcomes.

“In summary, in a 2-center study of a heavily pretreated population of patients with HL, administration of 2 x 108 [CD30-specific] CAR-T [cells]/m2 after lymphodepletion (with an alkylating agent and fludarabine) produced remarkable antitumor activity without significant toxicity,” concluded the researchers.


Ramos CA, Grover NS, Beaven AW, et al. Anti-CD30 CAR-T cell therapy in relapsed and refractory Hodgkin lymphoma [published online July 23, 2020]. J Clin Oncol. doi: 10.1200/JCO.20.01342