Tumor associated antigen specific T cells with nivolumab are safe and persist in vivo in rel/ref Hodgkin Lymphoma.

Hodgkin Lymphoma (HL) Reed Sternberg cells express tumor associated antigens (TAA) that are potential targets for cellular therapies. We recently demonstrated that TAA specific T cells (TAA-T) targeting WT1, PRAME and Survivin were safe and associated with prolonged time to progression in solid tumors. Hence, we evaluated whether TAA-T when given alone or with nivolumab were safe and could elicit anti-tumor effects in vivo in patients with relapsed/refractory (r/r) HL. Ten patients were infused TAA-T (8 autologous; 2 allogeneic) for active HL(n=8) or as adjuvant therapy after hematopoietic stem cell transplant (n=2) at cumulative doses ranging from 0.5 X107 to 4 X107cells/m2. Six patients received nivolumab priming before TAA-T and continued until disease progression or unacceptable toxicity. All 10 products recognized 1 or more TAAs, were polyfunctional and did not demonstrated autoreactivity. Patients were monitored for safety for six weeks following the TAA-T and for response until disease progression. The infusions were safe with no clear dose limiting toxicities. Patients receiving TAA-T as adjuvant therapy remain in continued remission at 2+ years. Of the 8 patients with active disease,1 patient had a complete response and 7 had stable disease at 3 months, 3 of whom remain with stable disease at 1 year. Antigen spreading and long-term persistence of TAA-T in vivo were observed in responding patients. Nivolumab priming impacted the TAA-T recognition and persistence. In conclusion, treatment of r/r HL patients with TAA-T alone or in combination with nivolumab was safe and produced promising results (clinicaltrials.gov NCT022039303 and NCT03843294).