Pretherapy metabolic tumor volume associates with response to CD30 CAR T cells in Hodgkin lymphoma.

Our group has recently demonstrated that chimeric antigen receptor T-cell therapy targeting the CD30 antigen (CD30.CAR-T) is highly effective in patients with relapsed and refractory (r/r) classical Hodgkin Lymphoma (cHL). Despite high rates of clinical response, relapses and progression were observed in a subset of patients. The objective of this study was to characterize clinical and correlative factors associated with progression free survival (PFS) after CD30.CAR-T cell therapy. We have evaluated correlatives in 27 patients with r/r cHL treated with lymphodepletion and CD30.CAR-T cells. With a median follow up of 9.5 months, 17 patients (63%) progressed, median PFS of 352 days (95% CI: 116 - not reached), and 2 patients died (7%), median OS not reached. High metabolic tumor volume (MTV, >60ml) immediately prior to lymphodepletion and CD30.CAR-T cell infusion was associated with inferior PFS (log rank p = 0.02), which persisted after adjusting for lymphodepletion or CAR-T dose (log rank p = 0.01 and p = 0.006, respectively). In contrast, receiving bridging therapy, response to bridging therapy, CD30.CAR-T expansion/persistence, and percentage of CD3+PD-1+ lymphocytes over the first 6 weeks of therapy were not associated with differences in PFS. In summary, this study reports an association between high baseline MTV immediately prior to lymphodepletion and CD30.CAR-T cell infusion and worse PFS in patients with r/r cHL. (ClinicalTrials.gov identifier: NCT02690545).