Ten-year results of a German Hodgkin Study Group randomized trial of standard and increased dose BEACOPP chemotherapy for advanced Hodgkin lymphoma (HD9)

Abstract

LBA8015 Background: The HD9 trial was designed to compare standard and dose escalated versions of a novel chemotherapy BEACOPP in advanced Hodgkin lymphoma. The previous analysis in 2004 showed improved tumor control and overall survival due to dose escalation. The present 10 year analysis in March 2007 aimed to update and confirm these results and to monitor late effects. Methods: Patients aged 16–65 years with untreated Hodgkin lymphoma stage IIB/IIIA and risk factors or stage IIIB/IV were randomized to (A) 4 double cycles COPP/ABVD, (B) 8 cycles standard-dose BEACOPP or (C) 8 cycles increased-dose BEACOPP (doxorubicin, cyclophosphamide and etoposide at 140%, 192% and 200% of standard doses, respectively), each followed by irradiation of initial bulky and residual disease. Accrual of at least 900 patients was planned so as to detect a 9–10% improvement in the primary endpoint, freedom from treatment failure (FFTF), with a power of 80% (alpha=5%). Results: 1196 of 1201 eligible, randomized patients were evaluable (261, 469 and 466 in arms A, B and C, respectively). Median follow-up times were 122, 111 and 107 months in arms A, B and C respectively (29–32 months longer than in 2004). Corresponding 10-year FFTF rates were 64%, 70% and 82% respectively (p<0.0001). FFTF was significantly better in the increased-dose arm than in the standard-dose arm (p<0.0001). 10-year overall survival rates were 75%, 80% and 86% respectively (p=0.0005). Overall survival was also significantly better in the increased-dose arm than in the standard-dose arm (p=0.0053). Death due to HL was 11.5%, 8.1% and 2.8% in arms A, B and C respectively. 74 second malignancies were documented: 1, 7 and 14 acute myeloid leukemias (AML); 7, 8 and 5 non-Hodgkin lymphomas; 7, 16 and 9 solid tumors/others in arms A, B and C respectively. The corresponding overall secondary malignancy rates were 6.7% , 8.9% and 6.8%. Conclusions: Even after 10 years, dose escalation of BEACOPP chemotherapy results in a stabilized significant improvement in long-term FFTF and OS rates. The risk of secondary AML, although increased in this study after increased-dose BEACOPP, amounts to 0.9% in the succeeding study with increased BEACOPP with 1502 patients and 4 years median follow-up. No significant financial relationships to disclose.