Abstract T083

Integrating E-HIPI and Interim PET to Refine Risk Stratification in Early-Stage Classic Hodgkin Lymphoma

Background: The E-HIPI is a baseline prognostic index developed to predict 2-year progression-free survival (PFS) in early-stage classic Hodgkin lymphoma (cHL). Since contemporary treatment is also guided by interim PET, we assessed whether PET after 2 cycles of chemotherapy (PET2) refines E-HIPI-based risk stratification.

Methods: We retrospectively analysed patients with early-stage cHL treated in 2007-2025 at 4 Italian centres with ABVD- or BEACOPP-based PET-guided approaches. E-HIPI was calculated using published coefficients for sex, maximum tumour diameter, albumin and hemoglobin, applying the original plausibility exclusions. PET2 was classified by Deauville score (DS), with DS 4–5 being considered as positive. Post-PET2 PFS was evaluated by landmark analysis among patients alive and progression-free at interim assessment. E-HIPI was analysed as continuous score and as low risk (<25th percentile) versus non-low risk. A dynamic classification was defined as: low E-HIPI/PET2-negative, non-low E-HIPI/PET2-negative, and PET2-positive.

Results: Overall, 264 patients were included; 130 (49%) were female and median age was 31 years. Stage II disease was present in 244 (92%), bulky disease in 84 (32%) and B-symptoms in 64 (24%). After a median follow-up of 62 months, 38 (14%) patients experienced progression or relapse and 8 (3%) died. E-HIPI showed moderate discrimination for 2-year PFS (C-index 0.654, 95% CI 0.55–0.75). PET2 was available in all patients; 242 (92%) were PET2-negative and 22 (8%) PET2-positive. Two-year post-PET2 PFS was 91% after negative PET2 and 35.6% after positive PET2 (HR [8.8, 95% CI 4.4-17.5; p<0.001). The combined model identified an ultra-low-risk group with low E-HIPI and negative PET2, with 2-year post-PET2 PFS of 96.8%, compared with 89.0% in non-low E-HIPI/PET2-negative patients and 35.6% in PET2-positive patients. Compared with all other patients, the low E-HIPI/PET2-negative group had reduced risk of progression or relapse (HR 0.2, 95% CI 0.05-0.97; p=0.04).

Conclusions: In this multicentre PET-guided early-stage cHL cohort, PET2 refined baseline E-HIPI risk stratification. Low E-HIPI combined with negative PET2 identified an ultra-low-risk subgroup with excellent disease control, supporting integrated baseline and early-response models for treatment de-escalation studies. PET2-positive patients may require alternative strategies or novel combinations.