Abstract T003

Durable Remissions and Late Immune-Related Toxicities After Frontline Pembrolizumab + AVD in Classic Hodgkin Lymphoma

Introduction: We previously reported efficacy of frontline pembrolizumab + AVD in CHL (Lynch et al, Blood 2023; ASH 2024). With emergence of highly effective frontline regimens that omit checkpoint inhibitors, better characterization of immune-related adverse events (irAEs), including management required, is needed.

Methods: We analyzed additional long-term follow-up of patients with previously untreated CHL treated with pembrolizumab plus concurrent AVD, as previously described (NCT03331341). In addition to survival outcomes, we analyzed treatment-emergent irAEs during and after study therapy.

Results: At median follow-up of 4.8 years, 5-year progression-free survival (PFS) and overall survival (OS) were 98% (95% CI 94%-100%) and 100% (95% CI 100%-100%), respectively. Five-year PFS was 100% (95% CI 100%-100%) in early-stage and 97% (95% CI 92%-100%) in advanced-stage disease.

Forty-one patients (82%) experienced at least 1 irAE during APVD, most commonly ALT elevation (29, 58%), rash (19, 38%), AST elevation (16, 32%), and hypothyroidism (4, 8%). Six patients (12%) required oral corticosteroids for an irAE during treatment. One patient with Guillain-Barré syndrome required IVIG and prolonged hospitalization.

Ten patients (20%) experienced a new irAE at least 30 days after the last pembrolizumab dose and completion of study therapy. These emerged at median 67 days (range, 33-858). Two grade 4 late irAEs were observed (pneumonitis and adrenal insufficiency), both requiring prolonged hospitalization.

Other late irAEs included hypothyroidism (5, 10%) and single cases of anterior uveitis, arthritis, AST elevation, colitis, hyperthyroidism, psoriasis, and rash.

All irAEs during or after treatment resolved except adrenal insufficiency (1, 2%) and hypothyroidism (7, 14%), requiring indefinite corticosteroid and levothyroxine replacement, respectively.

Conclusion: APVD was highly active in untreated CHL, with durable remissions in nearly all treated patients. irAEs, including grade ≥3 events, occurred during and after study therapy. Although most were reversible, there were late irAEs including grade 4 events as well as endocrinopathies that will require lifelong supplemention. Discussion of risks and benefits relative to other effective frontline regimens is important when selecting therapy for untreated CHL.