Abstract P012

Exploring the capability of the Advanced-Stage Hodgkin Lymphoma International Prognostic Index to predict the lack of an early complete metabolic response in a multicentric Italian cohort

The Advanced-Stage Hodgkin Lymphoma International Prognostic Index (A-HIPI) is a recently proposed prediction tool for classical Hodgkin Lymphoma (HL) making use of baseline prognostic factors to predict individual patient outcomes. The current therapeutic approach for HL is based on PET-guided ABVD, where the lack of an early response documented by a positive PET scan after 2 cycles (PET2) is a significant indicator of adverse risk. We therefore sought to evaluate the capability of the A-HIPI to identify patients at risk for a positive PET2 scan. A total of 355 patients treated for advanced-stage HL (stage ≥IIB) since 2004 in 4 Italian institutions were enrolled. All subjects were treated with PET-guided ABVD, and PET2 positivity was defined as a Deauville Score >3. The A-HIPI survival estimates were calculated as previously described [Rodday et al, JCO 2022]. Median age at diagnosis was 33 years, 49% of the patients were female, 81% presented with B symptoms and 38% had a bulky disease. After a median follow-up of 63 months, 8% of the patients died and 27% experienced disease relapse, with 5-yr overall-survival (OS) and progression-free survival (PFS) being 93% and 71%, respectively. PET2 positivity was reported in 18% cases, and significant differences in both 5-yr OS (94% vs 87%; p=0.03) and 5-yr PFS (80% vs 33%; p<0.001) were documented between PET2-positive and PET2-negative patients. Regarding the A-HIPI predicted risk, PET2-positive subjects exhibited a lower mean predicted survival probability for both OS (0.90 vs 0.92; p=0.048) and PFS (0.75 vs 0.77; p=0.049). Moreover, when comparing the predicted probability of PFS of PET2-positive individuals against their peers, a significantly higher proportion ranked in the highest risk quartile (37% vs 22%; p=0.017), a finding that was also confirmed when utilising the quartile cutoff derived from the discovery dataset in the original publication (43% vs 29%; p=0.039). Furthermore, the percentage of PET2-positive patients in each quartile increased together with the predicted risk (Q1: 37%, Q2: 23%, Q3: 17%, Q4: 18%). In conclusion, this work confirms the ability of the recently proposed A-HIPI to identify patients at higher risk of relapse, as we show that a lower predicted PFS is associated with a higher rate of PET2 positivity. In addition, the clustering of such patients into the higher risk quartile supports the usage for this cutoff in the design of future studies exploring risk-adapted strategies.