Positron emission tomography (PET)-guided omission of consolidative radiotherapy (RT) after 2+2 chemotherapy resulted in similar outcomes as standard combined-modality treatment among patients with newly diagnosed, early-stage, unfavorable Hodgkin lymphoma (HL), according to the results of a phase 3 trial published in Lancet Oncology.
The standard of care for the treatment of patients with early-stage, unfavorable HL is 2+2 chemotherapy comprising cyclophosphamide, doxorubicin, etoposide, procarbazine, prednisone, vincristine, and bleomycin (eBEACOPP) followed by doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), then consolidative RT. Because RT can result in long-term sequelae, the aim of this study was to determine if treatment efficacy can be maintained without RT among some patients.
In the open-label, phase 3 trial, 1100 patients with newly diagnosed, early-stage, unfavorable HL were randomly assigned to receive standard of care or PET-guided treatment, in which RT was omitted for patients who were PET negative after 4 chemotherapy cycles (PET4). The primary endpoint was progression-free survival (PFS). Noninferiority was defined as an absolute difference of 8% between the groups in the 5-year PFS estimates.
At baseline, the median age was 31 years, and 54% of patients were women. The proportion of patients with Ann Arbor stage IA HL was 47% in the standard treatment group compared with 3% in the PET4-guided group, with the remaining stages similar between the groups. The majority of patients had nodular sclerosis, followed by mixed cellularity and unspecified classic HL.
The investigators found PFS to be similar between the groups during a median follow-up of 46.2 months. The 5-year PFS was 97.3% and 95.1% in the standard-of-care and PET4-guided groups, respectively (hazard ratio [HR], 0.523; 95% CI, 0.226-1.211), which was within the prespecified margin of inferiority. Among patients who were PET4 negative, the 5-year PFS was 97.7% among patients in the standard treatment group and 95.9% among patients in the PET4-guided group who did not receive RT.
In a multivariate analysis, PET positivity with a Deauville score of 4 or higher was significantly associated with shorter PFS (HR, 10.47; 95% CI, 4.00-27.38; P <.0001).
The most common grade 3 to 5 adverse events during chemotherapy were hematologic effects such as thrombocytopenia and leucopenia. The most common grade 3 to 4 adverse events during RT were dysphagia and mucositis.
The authors concluded that “individualized PET4-guided treatment after 2+2 chemotherapy allows omission of radiotherapy…PET-guided therapy therefore substantially reduces the proportion of patients at risk of late effects from irradiation.”
Borchmann P, Plütschow A, Kobe C, et al. PET-guided omission of radiotherapy in early-stage unfavourable Hodgkin lymphoma (GHSG HD17): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22:223-234. doi:10.1016/S1470-2045(20)30601-X