Low-dose moderate hypofractionated radiotherapy for indolent non-Hodgkin lymphoma: a multicentre, single-arm, phase 2 trial.

Abstract

BACKGROUND Radiotherapy for indolent non-Hodgkin lymphoma has evolved to optimise the definitive dose while minimising toxicity. We aimed to assess the activity and safety of a hypofractionated low-dose radiotherapy regimen of 12 Gy in four fractions in patients with indolent non-Hodgkin lymphoma. METHODS This multicentre, single-arm, phase 2 trial study enrolled patients from four hospitals in China. Patients aged 18 years or older with newly diagnosed or relapsed stage I-IV indolent non-Hodgkin lymphoma (follicular lymphoma, marginal zone lymphoma, and low-grade lymphoma) and an Eastern Cooperative Oncology Group performance status of 0-3 were eligible. Patients underwent involved-site radiotherapy at a dose of 12 Gy in four fractions. The primary endpoint was the complete response rate 6 months after radiotherapy. All analyses were performed in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT05543070, with a four-month delay due to the COVID-19 pandemic; recruitment is complete and follow-up is ongoing. FINDINGS Between May 8, 2022, and Nov 8, 2023, 71 patients (with 73 target sites) were enrolled (median age 55 years [IQR 48-65]; 29 [41%] male and 42 [59%] female; and all were Asian). With a median follow-up of 19 months (IQR 16-22), the 6-month complete response was 95% (95% CI 87-98; 69 of 73 sites). The most common acute adverse events were grade 1 lymphopenia (20 [28%] of 71 patients) and grade 1 nausea (14 [19%] of 73 sites). The sole grade 3 or higher adverse event was grade 3 lymphopenia (eight [11%] of 71 patients). No treatment-related deaths were noted. INTERPRETATION The regimen of 12 Gy in four fractions is safe and shows promising activity as a local treatment for patients with indolent non-Hodgkin lymphoma. Given the retrospective registration of the trial, further studies evaluating the efficacy of this strategy are warranted. FUNDING The Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National High Level Hospital Clinical Research Funding, and the Beijing Hope Run Special Fund of Cancer Foundation of China.