Anti-CD30 Chimeric Antigen Receptor T Cell Therapy for CD30⁺ Relapsed/Refractory Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma Patients

Chimeric antigen receptor T (CAR-T) cell therapy had shown remarkable efficacy in B-cell acute lymphoblastic leukemia and several B-cell lymphomas using CD19/22 antigen as target. Similarly, CD30 was found over-expressed on all stage of the cells in classical Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). Given the encouraging clinical success achieved by CD30 monoclonal antibody brentuximab vedotin, targeting CD30 with CAR-T cells would be a promising therapeutic approach for these populations. Here we conducted an open-label, single-center and single-arm pilot study, aimed to evaluate the feasibility and safety of anti-CD30 CAR-T cell therapy relapsed/refractory in HL and ALCL patients. This trial is registered with ChiCTR, number ChiCTR-OPN-16009069.

From August, 2016 to May, 2018, 4 HL and 2 ALCL patients with a median age of 26.5 years (range, 22-55 years) were enrolled in this study. Disease diagnosis and CD30expression was confirmed again by pathology and immunohistochemistry at enrollment. All the patients had relapsed or primary refractory disease, after at least two lines of systemic therapy. A pre-conditioning FC (fludarabin 25mg/m², cyclophosphamide 20mg/kg for 3 days) regimen was give before CAR-T cell infusion. A total dose of 0.7-2.45×10⁷ (median 1.175×10⁷) per kg of CAR-T cells was infused over 3 to 7 consecutive days. The CAR transgene copy, representing CAR-T cells expansion, reached the peak at about 1 week after first administration, and then decreased. CAR transgene copy was still above 100 per μg genomic DNA in peripheral blood even 6 months after infusion. 5/6 (83.3%) patients had grade 0-1 cytokine release syndrome (CRS), with fever lower than 39℃ and duration less than 2 week. Levels of cytokines, including interleukin 6, ferritin and C-reactive protein were monitored. The maximum fold change of the cytokines from baseline was less than 10. No sign of neurotoxicity, bone marrow suppression or other adverse events were observed. The toxicity was generally tolerable, except for one HL patient, who experienced grade 4 CRS, eventually died from pneumorrhagia at the 20^th day of infusion. The other 5 patients all achieved complete remission (CR) successfully. PET scan showed a CR status as early as the first month after infusion. Although relapse was observed in one HL patient 2 months after infusion, there were 3 of them remained CR state for over 1 year according to PET scan. The median progression free survival was 7 months.

In conclusion, our work demonstrated that CD30 CAR-T cell therapy is efficient and safe for HL and ALCL patients, providing a new option in treating CD30⁺ relapsed/refractory lymphomas, while a lager study scale was further demanded in our trial to obtain more robust support.