Abstract P018

Interim PET remains clinically informative during frontline nivolumab-based therapy in advanced-stage classical Hodgkin lymphoma

Background: Interim PET is essential for response-adapted frontline treatment in classical Hodgkin lymphoma, but its interpretation may be complicated by PD-1 blockade. We evaluated whether PET2, supported by quantitative PET parameters, remains informative for treatment adaptation during nivolumab-based treatment.

Methods: We conducted a prospective single-center study (NCT07209059) evaluating a PET-adapted nivolumab-based first-line strategy in advanced-stage classical Hodgkin lymphoma (AS-cHL). 44 previously untreated pts were enrolled. All pts received two induction cycles of nivolumab 40mg (N40) plus EACOPD-14. Patients achieving CMR (DS 1–3) at PET2 received N40-AVD consolidation followed by 2 cycles of N40, whereas patients with PMR (DS 4–5) continued N40-EACOPD-14 up to 6 cycles. RT was omitted in all patients. Quantitative PET analysis included changes in SUVmax (ΔSUVmax) and metabolic tumor volume (ΔMTV) and was available for 31 patients.

Results: All 44 pts completed induction therapy and underwent PET2 assessment. CMR was achieved in 36/44 patients (82%), while 8/44 (18%) demonstrated PMR. No DS5 cases were observed. All PMR cases showed low-volume residual uptake confined to mediastinal lesions. One patient experienced pseudoprogression after 2 cycles of N40-AVD. Quantitative PET analysis demonstrated profound early metabolic responses. Median ΔSUVmax was −84.5% (IQR, −87.3% to −81.4%) in pts achieving PET2 CMR and −72.8% (IQR, −78.6% to −70.6%) in pts with PET2 PMR. Importantly, near-complete elimination of MTV was observed irrespective of PET2 category, with ΔMTV of 100% in 30/31 pts and 99% in the remaining patient. At data cutoff, 38 patients had completed treatment and all achieved EOT CMR. No relapses or disease progression have been observed. Me FU was 10.2 months.

Conclusions: This PET-adapted nivolumab-based strategy demonstrated high early metabolic response rates and enabled chemotherapy de-escalation with radiotherapy omission in AS-cHL. Despite residual PET2 DS4 uptake, metabolic tumor burden was nearly completely eliminated, suggesting treatment-related inflammatory activity rather than substantial viable lymphoma. Quantitative PET parameters may help refine PET2 interpretation during PD-1-containing treatment regimens and improve response assessment beyond conventional Deauville scoring.