COMPARING INTENSITY OF CHEMOTHERAPY FOLLOWED PET-GUIDED RADIOTHERAPY IN PATIENTS WITH ADVANCED STAGE HODGKIN LYMPHOMA: FINAL RESULTS OF THE GHSG HD15 TRIAL

Sborník

Background. Intensified chemotherapy with eight cycles of BEACOPPescalated in advanced stage Hodgkin lymphoma (HL) is highly effective but also associated with relevant treatment related toxicity. In addition, the need for radiotherapy in this setting is unclear. To reduce toxicity without losing efficacy the GHSG thus conducted the prospective randomized clinical HD15 trial investigating two less intensive chemotherapy variants, followed by PET guided radiotherapy. Methods. Between January 2003 and April 2008, 2182 patients with newly diagnosed, histology-proven HL aged 18-60 years were included. Patients in Ann-Arbor stage IIB with large mediastinal mass or extranodal lesions, or those in stage III or IV were randomly assigned to receive either eight cycles of BEACOPP_escalated (8B_esc), six cycles of BEACOPP_escalated (6B_esc), or eight cycles of BEACOPP₁₄ (8B₁₄). After completion of chemotherapy, patients in partial response (PR) with a persistent mass measuring 2.5 cm or more were assessed by PET. Only patients who were positive on centrally-reviewed PET scan received additional radiotherapy (RT) with 30Gy. The study was designed to show non-inferiority for the primary endpoint, freedom from treatment failure (FFTF).Results. The full analysis set comprised 2126 patients. Baseline characteristics were well balanced between groups. Hematological toxicities occurred in 92.4% (8B_esc), 91.7% (6B_esc), and 79.7% (8B₁₄) ofcases. After a median follow-up of 48 months, there were 53 deaths (7.5%) in the 8B_esc group, 33 (4.6%) in the 6B_esc group and 37 (5.2%) in the 8B₁₄ group. There were 72 secondary cancers including 29 secondary AML/MDS, 19 (2.7%) after 8B_esc, 2 (0.3%) after 6B_esc and 8 (1.1%) after 8B₁₄. Complete response (CR) was achieved in 90.1% of patients after 8B_esc, in 94.2% after 6B_esc and in 92.4% after8B₁₄ (p=0.01). FFTF at 5 years was 84.4% in the 8B_esc group, 89.3% in the 6B_esc group (97.5% confidence interval (CI) for difference 0.5% to 9.3%), and 85.4% in the 8B₁₄ group (97.5 CI -3.7% to 5.8%), respectively (see figure). Overall survival at five years was 91.9%, 95.3%, and 94.5%, and was also better with 6B_esc compared to 8B_esc (97.5% CI 0.2% to 6.5%). PFS results were similar to FFTF. PET scans performed after chemotherapy were centrally reviewed in 822 patients of whom 739 were in PR with residual mass ≥ 2.5 cm having no other exclusion criteria. 548 patients were PET-negative (74.2%) and 191 were PET-positive (25.8%). Importantly, PFS was comparable between patients in CR or those in PET-negative PR after chemotherapy with 4-year PFS rates of 92.6% and 92.1%, respectively. Only 11% of all patients in HD15 received additional RT as compared to 71% in the prior HD9 study. Conclusions. Six cycles of BEACOPP_escalated followed by PET-guided RT are more effective and less toxic compared to 8 cycles in patients with advanced stage HL. In particular, critical toxicities observed with 8 cycles wherereduced with 6 cycles of BEACOPP_escalated. PET performed after chemotherapy can guide the need of additional RT in this setting and reduces the number of patients requiring RT.

Haematologica, 2012; 97(s1):  455