Integrated Prognostic Modelling with the CALLY Index and Interim PET/CT in Hodgkin Lymphoma

Background/Objectives: Interim 18F-FDG PET/CT is the most powerful prognostic tool in Hodgkin lymphoma but is only available after 2 cycles and does not guide initial treatment. The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel composite index of inflammation, nutrition, and immunity, measurable at diagnosis, but has not been studied in Hodgkin lymphoma (HL). We tested whether baseline CALLY could predict interim PET response and survival and whether combining the two provides additional information over either alone. Methods: A retrospective study of 180 consecutive patients with newly diagnosed Hodgkin lymphoma at a single center was performed. CALLY was defined as albumin (g/L) × lymphocytes (×109/L)/CRP (mg/L). Interim PET after two cycles was scored using the Deauville scale (4–5 positive). The endpoints were progression-free survival (PFS) and overall survival (OS). Results: Median follow-up was 30.5 months, 32 patients had a PFS event, and 16 died. Interim PET was positive in 31/163 patients (19.0%). Baseline CALLY was lower in PET-positive patients compared with PET-negative patients (median 1.16 vs. 3.34; p = 0.022; area under the curve 0.635, modest discrimination). Interim PET positivity (29.8% vs. 13.0%; OR 2.84, 95% CI 1.26–6.42), 24-month PFS (66.9% vs. 89.8%; p = 0.001) and OS (84.8% vs. 95.5%; p = 0.022) were reduced below a Youden-derived threshold of 1.5. CALLY was not independently prognostic after adjustment for interim PET (PFS hazard ratio [HR] 1.86, 95% CI 0.79–4.37; p = 0.157). A three-tier exploratory model combining both factors separated 24-month PFS into 94.5% (n = 87), 79.6% (n = 53), and 41.2% (n = 17) (p < 0.001; high- vs. low-risk HR 9.48, 95% CI 3.59–25.04), although the intermediate tier was not statistically different from the low-risk tier. Conclusions: In this cohort, baseline CALLY provides a low-cost pre-treatment correlate of early metabolic response and outcome, with numerically greater discrimination than the International Prognostic Score. Its prognostic signal seems largely mediated through the interim PET response, and therefore it should complement, not replace, interim response assessment. Discrimination was modest, and the integrated model is exploratory and requires prospective multicenter validation in contemporary protocols before clinical use.