Response-guided first-line therapy and treatment of relapse in aggressive lymphoma: 10-year follow-up of the PETAL trial

The 'Positron emission tomography-guided therapy of aggressive non-Hodgkin lymphomas' trial (PETAL; ClinicalTrials.gov NCT00554164) investigated whether treatment intensification after two cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; plus rituximab [R] for CD20-positive lymphomas) improved survival in aggressive non-Hodgkin lymphoma. A total of 754 patients (87.5%) had a negative and 108 (12.5%) had a positive interim PET scan. Interim PET-positive patients were randomly assigned to receive another 6 (R-)CHOP cycles or 6 blocks of a more intensive protocol. Interim PET-negative patients received another 4 cycles of R-CHOP with or without two additional doses of rituximab. After a median follow-up of four years, treatment intensification had not improved outcome. These results were confirmed after 10.3 years of follow-up. The present analysis also describes the management of relapse that was part of the study. Among 240 relapsing patients, 94 of 133 autologous transplantation-eligible patients (70.7%) and 16 of 107 ineligible patients (15.0%) received the salvage treatments recommended in the study protocol. Adherence to recommendations had no impact on outcome. Best results were seen after allogeneic transplantation, followed by autologous transplantation and treatment without transplantation (5-year overall survival rate, 64.3% versus 45.5% versus 22.6%), but patients undergoing allogeneic transplantation were significantly younger and their disease was well controlled at the time of transplantation. Early outcome prediction by interim PET, alone or in combination with other methods, is a powerful tool to investigate the value of immunological treatment options for patients with a poor response to chemotherapy.