Clinical outcomes and safety of the immune checkpoint inhibitor rechallenge in Hodgkin lymphoma: an off-trial analysis

Immune checkpoint inhibitors (ICIs) are effective in classical Hodgkin lymphoma (cHL), but immune-related adverse events (irAEs) may lead to treatment interruption in some patients. We conducted a retrospective cohort study of 145 patients with cHL treated with ICIs between 2015 and 2024. Cohort 1 included 130 patients in which 15 received ICI rechallenge within the same treatment line following irAE-related interruption and 115 who did not undergo rechallenge. Another 15 patients who underwent ICI rechallenge in a subsequent line of therapy comprised cohort 2. In cohort 1, PFS and DOR did not differ between rechallenged and non-rechallenged patients (HR 1.7, 95% CI 0.31-9.3, p = 0.55; HR 2.7, 95% CI 0.24-31.2, p = 0.42, respectively). Recurrent irAEs occurred in 20%, with recurrence of the same irAE in 7% in cohort 1. In cohort 2, 53% had refractory disease, whereas 47% responded to initial ICI and were subsequently rechallenged at progression. The median PFS was 7.4 months (95% CI: 5.0-NE) and 13.5 months (95% CI 8.1-46.7), respectively. ICI rechallenge after irAE-related interruption was feasible in selected patients.