Checkpoint inhibitors, obinutuzumab plus PET-adapted ultra-low dose nodal radiotherapy yield high efficacy in treatment-na&#239;ve follicular lymphoma: Results from the phase II &#39;FLUORO&#39; study

Martynchyk, A; Chong, G; Khor, R; Lee, D; Lee, ST; Scott, AM; Grobler, AC; Campbell, BA; Thachil, T; Manos, K; Douglas, G; Romano, A; Palmer, JB; Burgess, M; Keane, C; Hawkes, EA

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

Author(s): Martynchyk, A; Chong, G; Khor, R; Lee, D; Lee, ST; Scott, AM; Grobler, AC; Campbell, BA; Thachil, T; Manos, K; Douglas, G; Romano, A; Palmer, JB; Burgess, M; Keane, C; Hawkes, EA;
Details: Publication Year 2026-06,Volume 208,Issue #6,Page 2026-2035
Journal Title: British Journal of Haematology
Publication Type: Research article
Abstract: 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.
Publisher: Wiley
Keywords: Humans; *Antibodies, Monoclonal, Humanized/therapeutic use/administration &; dosage/adverse effects; *Lymphoma, Follicular/therapy/mortality/diagnostic imaging/drug; therapy/radiotherapy; Female; Middle Aged; Male; *Positron-Emission Tomography; Adult; Aged; *Immune Checkpoint Inhibitors/therapeutic use/administration & dosage/adverse; effects; Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects; Treatment Outcome; clinical trial; follicular lymphoma; immunotherapy; radiotherapy
Department(s): Radiation Oncology
Publisher's Version: https://doi.org/10.1111/bjh.70468
Open Access at Publisher's Site: https://doi.org/10.1111/bjh.70468
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-04-28 05:52:37

Last Modified: 2026-06-30 03:12:31