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 (ClinicalTrials.gov Identifiers: NCT02690545) and phase 1 RELY-30 (ClinicalTrials.gov 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.
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.