Autologous T cells expressing CD30 chimeric antigen receptors for relapsed or refractory Hodgkin's lymphoma: an open-label phase I trial
Mené sur 18 patients atteints d'un lymphome hodgkinien réfractaire ou récidivant, cet essai de phase I évalue la toxicité et l'activité antitumorale d'une injection de lymphocytes T autologues modifiés pour exprimer des récepteurs chimériques ciblant l'antigène CD30
Purpose:Relapsed or refractory Hodgkin's lymphoma is a challenge for medical oncologists because of poor overall survival. We aimed to assess the feasibility, safety, and efficacy of CD30-targeting CAR T cells in patients with progressive relapsed or refractory HL. Experimental Design:Patients with relapsed or refractory HL received a conditioning chemotherapy followed by the CART-30 cell infusion. The level of CAR transgenes in peripheral blood and biopsied tumor tissues was measured periodically according to an assigned protocol by quantitative Polymerase Chain Reaction. Results:Eighteen patients were enrolled; most of whom had a heavy treatment history or multiple tumor lesions, and received a mean of 1∙56×10⁷ CAR-positive T cell per kg (SD 0.25, range 1∙1-2∙1) in total during infusion. CART-30 cell infusion was tolerated, with grade {greater than or equal to}3 toxicities occurring only in 2 of 18 patients. Of 18 patients, seven achieved partial remission, six achieved stable disease. An inconsistent response of lymphoma was observed: lymph nodes presented a better response than extranodal lesions, and the response of lung lesions seemed to be relatively poor. Lymphocyte recovery accompanied by an increase of circulating CAR T cells (peaking between 3 and 9 days after infusion) is a probable indictor of clinical response. Analysis of biopsied tissues by qPCR and immunohistochemistry revealed the trafficking of CAR T cells into the targeted sites, and reduction of the expression of CD30 in tumors. Conclusions:CART-30 cell therapy was safe, feasible, and efficient in relapsed or refractory lymphoma and guarantees a large-scale patient recruitment.