Unusually long remission in two patients with follicular lymphoma receiving immunomodulating therapeutic cancer vaccines.

The immune checkpoints programmed death-ligand (PD-L)1 and PD-L2 are expressed in follicular lymphoma (FL), yet immune checkpoint blocking antibodies have failed in FL. We previously initiated a phase I immune modulating vaccination (IMV) trial targeting PD-L1 and PD-L2 in patients with advanced follicular lymphoma. The study suggested a clinical effect of the vaccine, however due to relatively short follow-up time and a heterogeneous patient population no clear conclusions could be made after the trial. In this study we present follow-up data on the eight patients included in the trial. Notably, two patients displayed an unusual disease history after completion of the vaccination trial. One patient had experienced two relapses at two years after diagnosis, then received vaccines after third line therapy and subsequently remained treatment-free for five years after vaccinations. The other patient who entered the vaccine trial after third line therapy remains in complete response at 6.5 years after the vaccination trial. Longitudinal immune monitoring in these two patients demonstrated persistent, functionally active vaccine-specific CD4⁺ and CD8⁺ T-cell responses years after vaccine completion. These results suggest a disease modifying effect of targeting PD-L1 and PD-L2 by IMV in FL. Trial registration number: NCT03381768. Date of registration: December 22, 2017.