Results from the TRANSCEND NHL 001 trial have demonstrated promising results for a novel form of CAR T-cell therapy, termed JCAR017, in patients with poor-prognosis relapsed or refractory non-Hodgkin lymphoma. The findings were presented recently at the 2018 ASCO-SITC Clinical Immuno-Oncology Symposium (25–27 January, CA, USA).
JCAR017 is a CD19 directed CAR T-cell product, comprising individually formulated CD4+ and CD8+ suspensions, which are administered in a flat dose.
The trial was a multicentre study including dose-finding and dose-expansion cohorts. Participants included a ‘core’ group with high-grade B-cell lymphoma or high-grade B-cell lymphoma after two lines of therapy. The full cohort also included patients with primary mediastinal B-cell lymphoma and follicular lymphoma grade 3B, or aggressive lymphoma that had originated from chronic lymphocytic leukemia or marginal zone lymphoma.
In total, 140 participants underwent leukapheresis, 108 of whom were treated with JCAR017. The overall response rate to JCAR017 was 74%, with 52% demonstrating a complete response.
Within the core group, response rate was 76% in those receiving a dose level of 5 x 10⁷ cells in a single dose (DL1S) and 81% for those receiving 1 x 10⁸ in a single dose (DL2S). Higher complete response levels were observed in DL2S, 63%, compared with 47% for those receiving DL1S. 50% of DL2S patients who had achieved complete response had maintained it within 6 months of treatment.
It was observed that the 6-month overall survival for the full cohort was 86%, with those who reached complete response achieving an overall survival rate of 94%.
Overall , the authors state that the updated efficacy and the preliminary safety profile for JCAR017, supports potential outpatient administration in relapsed/refractory aggressive B- non-Hodgkin lymphoma patients.
A consequent pivotal cohort utilizing DL2S is currently enrolling patients, aiming to only examine those with diffuse large B-cell lymphoma.
Stephen Gottschalk (St. Jude Children’s Research Hospital, TN, USA), the discussant of the session, remarked upon the outstanding questions to be addressed: “How durable are these responses? What is the mechanism of failure? If patients do achieve a long-term complete response, when is it safe to deplete CD19 CAR T cells to allow the recovery of normal B cells?”
A subsequent analysis based on the study was also presented at the symposium. In this study, JCAR017 demonstrated increased CAR T-cell expansion and persistence and higher durability of response at higher dose levels, with manageable toxicities. CAR T-cells were also detected at time of relapse, suggesting potential opportunities for future combination clinical trials.
Abstract presenter Tanya Siddiqi (City of Hope National Medical Center, CA, USA) explained these results: “The theory is that these patients with a higher tumor burden and a higher inflammatory state have such a rapid expansion […] that those T cells may be getting exhausted or dying out very quickly and patients lose their response.”
Future research aims to refine patients to be examined in cohorts, with the potential for adding in control mechanisms that may work via apoptotic, cytolytic or antiproliferative approaches, amongst others.