C031 | 10-YEAR UPDATE OF THE HD0607 STUDY ON ADVANCED-STAGE HODGKIN LYMPHOMA. FOCUS ON LONG-TERM RESPONSES AND LATE TOXICITIES.

Background. The HD0607 clinical trial contributed significantly to establishing the PET/CT-guided escalation approach in patients with advanced-stage (IIB-IV) classical Hodgkin lymphoma (HL). As our approach to advanced-stage HL improves and higher cure rates are achieved, late therapy-related toxic effects need to be evaluated. Methods and Aim. This update of the HD0607 study was conducted to report long-term efficacy results and rates of second primary malignancies (SPM) and cardiovascular events (CVE). Enrollment criteria, treatment details and trial endpoints have been previously reported [Gallamini A et al. JCO 2018 and 2020]. Results. Updated follow-up data was available for 618 patients (72% of the originally enrolled subjects) with no statistical difference between baseline features. After a median follow-up time of 120 months (range 1-191), the PET/CT-guided approach was associated to a 10-year PFS and OS of 77.6% and 92.1%, respectively. Significant differences in PFS were identified between interim PET/CT (iPET) negative (Deauville score, DS <=3) and iPET (DS 4-5) positive patients, with a 10-year PFS of 83.1% and 56.7% [HR 3.43 (2.42-4.88)]. Furthermore, the lack of impact of the omission of consolidative radiotherapy (RT) for subjects with a LNM and a negative end-of-treatment PET/CT was confirmed [HR 0.54 (0.20-1.45)]. Stage IV disease remained a significant predictor for both worse PFS [HR 1.87 (1.33-2.63)] and OS [HR 2.69 (1.50-4.80)]. A total of 25 SPMs were recorded in 4% of the patients. The estimated 10-year cumulative incidence was 3.4%, and no significant differences were identified in patients who received therapy intensification with BEACOPPesc [HR 1.60 (0.67-3.80)] and in patients who did or did not undergo consolidative radiotherapy (RT) [HR 0.54 (0.16-1.81)]. Similarly, CVEs were infrequent, with an estimated 10-year cumulative incidence of 2.2% (14 events among 2% of the evaluable population), with no significative differences between PET2-negative patients and their counterparts [HR 0.76 (0.17-3.39)] and the two arms of the RT randomization [HR 1.53 (0.50-4.73)]. Conclusions. As the HD0607 study reaches the 10-year follow-up landmark, a chemotherapeutic approach seems to be feasible in patients without stage IV HL. Long term safety data are reassuring, and confirm that a PET-driven strategy is not only effective but may reduce the excess of late SPM and CVE observed in patients treated with more intensive front-line programs.