Outcomes of Immune Checkpoint Inhibitor Rechallenge in Relapsed and/or Refractory Hodgkin Lymphoma Open Access

• ICI rechallenge in relapsed/refractory classical Hodgkin lymphoma can lead to high response rates comparable to uninterrupted ICI therapy.

• ICI rechallenge had acceptable safety profiles with grade 3–5 AEs occurring in 31%.

Immune checkpoint inhibitors (ICIs) have revolutionized therapy for relapsed and/or refractory (R/R) Hodgkin lymphoma (HL)​. Some patients discontinue ICIs after initial response or due to immune-related adverse events (irAEs). Efficacy and safety of ICI rechallenge, defined as reintroducing ICIs after prior discontinuation, remain unclear. A systematic literature search was performed through January 10, 2025, following PRISMA guidelines (PROSPERO CRD42023403204). Studies reporting outcomes of ICI rechallenge in patients with R/R HL were included. Data on overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS), and treatment-related adverse events (AEs) were extracted. Pooled response rates and 95% confidence intervals (CI) were calculated. Two-hundred and seven patients from 17 studies were included. The pooled ORR was 63% (95% CI: 55–70%) with a CR rate of 43% (35–52%). Median PFS after rechallenge was 13.3 months (95% CI: 7.9–18.8). Any grade and grade 3–5 AEs occurred in 47% (95% CI: 17–80%) and 31% (95% CI: 23–40%), respectively. ICI rechallenge in R/R cHL can lead to high response rates and durable remissions comparable to uninterrupted ICI therapy with acceptable safety profiles. This strategy may be a viable option, although careful patient selection and monitoring are still necessary.