Long-term results of the HD0607 trial on interim PET-adapted treatment of advanced-stage Hodgkin lymphoma beyond 10 years of follow-up.

Abstract

In advanced-stage classic Hodgkin lymphoma (cHL), risk-adapted therapeutic strategies have proven to be safe and effective, although long term efficacy data are lacking. Furthermore, some concern persists about the risk of late occurrence of second primary malignancies (SPM) or cardiovascular events (CVE) in survivors. HD0607 is a phase-2 multicenter prospective clinical trial enrolling stage IIB-IV patients with untreated cHL. All subjects started treatment with 2 ABVD cycles and subsequently underwent an interim PET (PET-2). PET-2 positive patients [Deauville score (DS) 4-5] switched to BEACOPP escalated/baseline (4 + 4 cycles), while PET-2 negative patients (DS ≤ 3) were treated with 4 more ABVD cycles. Patients with a large nodal mass (LNM, defined as ≥5 cm in diameter) at baseline and both PET-2 and end-of-chemotherapy (EoT) PET negative scans were randomly allocated to receive consolidation radiotherapy (cRT) or no further therapy (NFT). This clinical trial has been registered in the European Union Drug Regulating Authorities Clinical Trials Database under the EudraCT number 2007-007168-94 and is publicly available on the EU Clinical Trials Register. Out of 782 enrolled subjects, 630 (81%) had a negative while 150 (19%) a positive PET-2. After a median follow-up of 11 years (IQR 7-13 years), 102/630 patients with a negative PET-2 (16.2%) and 57/150 (38.0%) with a positive PET-2 progressed or relapsed. The 10-years PFS and OS were 83% and 96% vs. 58% and 85% (p < 0.0001) for PET-2 negative and PET-2 positive patients, respectively. Patients randomized to NFT did not have an increased risk of relapse or death (PFS HR 0.67, 95%CI 0.31-1.43; OS HR 0.49, 95% CI 0.09-2.68). During the follow-up 28 (3.6%) and 16 (2.1%) patients developed a SPM and CVE, respectively. After more than a decade of follow-up the HD0607 trial confirmed: i) the long-term predictive value of PET-2; ii) the persistent and sustained remission rate of PET-2 negative patients; iii) no PFS benefit consolidation RT over a non-FDG avid LNM; iv) the cumulative low incidence of SPM and CVE in the enrolled patients. This work was supported by Associazione Italiana per la Ricerca sul Cancro (AIRC), IG n.2013 to AG, by Associazione Italiana Lotta alla Leucemia (AIL) sezione di Bergamo and by a Research Grant of Cassa di Risparmio di Cuneo. Progetti di Rilevanza Nazionale PRIN PNRR (P2022PSMX4), STARS UNIPD 2023 to AV.