ISHL10 Abstract T001

BEACOPP escalated followed by radiotherapy of initial bulk or residual disease in advanced-stage Hodgkin Lymphoma: long-term follow-up of the GHSG HD9 and HD12 trials

Introduction: The HD9 trial had established 8xBEACOPPescalated followed by radiotherapy (RX) of initial bulk or residual tumors as standard of care for advanced Hodgkin Lymphoma (HL) at that time. The successor study of HD9, HD12, evaluated a reduction of chemotherapy and RX. Since the long-term safety and efficacy of BEACOPPescalated and RX has been debated, we report the HD9 and HD12 long-term follow-up.

Patients and methods: All patients had advanced HL. 1,282 HD9-patients were randomized between 8xCOPP/ABVD, 8xBEACOPPbaseline, and 8xBEACOPPescalated. 1,670 HD12-patients were randomized between 8xBEACOPPescalated, and 4xBEACOPPescalated followed by 4xBEACOPPbaseline (“4+ 4”), both with or without RX to initial bulk and residual disease.

Results: In HD9-patients treated with COPP/ABVD, BEACOPPbaseline, and BEACOPPescalated, the 15-year progression-free survival (PFS) was 57%, 66.8%, and 74% with overall survival (OS) rates of 72.3%, 74.5%, and 80.9%, respectively. BEACOPPescalated remains significantly better than COPP/ABVD in terms of PFS (P<0.0001) and OS (P=0.02). A total of 123 second malignancies corresponding to 15-year cumulative secondary malignancy incidences of 7.2%, 13%, and 11.4% were reported for COPP/ABVD, BEACOPPbaseline, and BEACOPPescalated, respectively, without a difference between COPP/ABVD and BEACOPPescalated (p=0.5). Standardized incidence ratios (SIR) with 95%-CI were 2.0[1.2-3.2], 2.6[1.9-3.4] and 2.6[1.9-3.4]. The 10-year PFS and OS rates in the two HD12 chemotherapy groups were not significantly different with 82.6% and 87.3% in the BEACOPPescalated group and 80.6% and 86.8% in the 4+4 group, respectively. However, omitting RX resulted in an significantly inferior 10-year PFS of 83.5% in no RX patients with initial bulk/residual disease compared to RX (88.6%, difference -5.1%; 95%-CI,-9.9% to -0.4%, hazard ratio [HR] 1.47; figure 1) and a trend towards inferior OS in no RX patients (RX 93%; no RX 90.2%; difference -2.7%; 95%-CI,-6.5% to 1%). Patients with residual lesions without RX had an inferior OS as compared to patients with RX (as treated comparison: RX 94.4%; no RX 88.4%; difference -6%; 95%-CI,-11.4% to -0.5%).

Conclusions: The superiority of BEACOPPescalated to COPP/ABVD is confirmed by this HD9 long-term analysis. The HD12 long-term analysis shows an inferior PFS and trend towards inferior OS in patients in the no RX groups, particularly in patients with residual lesions.