Advanced stage classical Hodgkin lymphoma patients with a positive interim-PET (PET-2) Deauville score 5 after 2 ABVD cycles: a pooled analysis of three multicenter trials

PET after 2 ABVD cycles (PET-2) is widely adopted to select patients with classical Hodgkin lymphoma (cHL), who might benefit from intensifying or de-escalating therapy. Prolonged progression-free survival (PFS) has been reported in PET-2 positive patients switched to escalated BEACOPP (eBEACOPP) or BEACOPP-14. Nevertheless, the subgroup of patients with a PET-2 scored 5 according to Deauville score (PET-2 DS5) are known to poorly benefit from treatment intensification. To elucidate PET-2 DS5 outcome along with possible predictive factors of response to intensification, a pooled analysis from three multicenter trials, GITIL/FIL HD0607, RATHL, and SWOG S0816, was conducted. PFS and overall survival (OS) were assessed after 41-month median follow-up, the prognostic value of clinical, laboratory, and PET parameters at diagnosis was evaluated. Among 2231 patients, 136 (6%) PET-2 DS5 patients were identified. Their 3-year PFS was 32% (95% CI, 25–42), while the 3-year OS was 82% (95% CI, 75–89). In multivariate analysis low lymphocyte (< 600/mm3) counts were adversely associated with PFS, whereas age ≥ 45 years and leukocytes cells count <15 × 103/μL were barely associated with short OS. The study confirms on a suitable cohort of PET-2 DS5 patients, that this high-risk cHL subgroup has an inadequate response to treatment intensification. Nevertheless, PET-2 DS5 patients may still have good outcome after subsequent salvage treatments with > 80% survival at 3 years, thus excluding a real disease refractoriness. Few distinct parameters may have specific prediction for PFS or OS.