Checkpoint inhibitors, obinutuzumab plus PET-adapted ultra-low dose nodal radiotherapy yield high efficacy in treatment-naïve follicular lymphoma: Results from the phase II 'FLUORO' study.

Follicular lymphoma (FL) first-line chemoimmunotherapy yields high efficacy but serious toxicity in 65% of patients. In high tumour burden treatment-naïve FL, we aimed to exploit known immunostimulatory and cytotoxic properties of combination checkpoint inhibition (atezolizumab) and obinutuzumab (6 cycles) with positron emission tomography (PET)-adapted ultra-low dose radiotherapy (RT; 4Gy) to all PET-avid sites after cycle 2, followed by 2 years of obinutuzumab maintenance. Sixteen eligible patients were enrolled (15 evaluable for response) to our Phase II trial (NCT04962126). Median age was 53 years with 94% intermediate/high Follicular Lymphoma International Prognostic Index (FLIPI) score. The primary end-point of complete response (CR) was achieved in 93% (95% confidence interval [CI]: 70%-99%) with objective response rate (ORR) of 100% (95% CI: 75%-100%). With 41-month median follow-up, 3-year progression-free survival (PFS) was 80% (95% CI: 55-93) and OS was 100% (95% CI: 79.6-100). Grade 3-4 adverse events occurred in 31% of patients (2 immune-related). Baseline PET radiomics and immune transcriptomics demonstrated profiles suggesting promise as predictive markers of immunotherapy response, consistent with our prior findings. The novel multimodality combination of obinutuzumab, atezolizumab and ultra-low dose nodal RT in treatment-naïve FL has promising efficacy and safety, offering a potential novel chemo-free option. Further studies using low-cost RT to augment immunotherapy are warranted. This trial was registered in clinicaltrials.gov, registration number: NCT04962126.