Results from the phase 2 FLUORO study suggest that treatment with the immunotherapies atezolizumab and obinutuzumab combined with PET-adapted ultra-low dose radiotherapy is safe and effective in treatment-naïve patients with low-grade follicular lymphoma (FL).
The results were published in the British Journal of Haematology.
In the FLUORO study, a multicenter, single-arm, phase 2 trial, 16 treatment-naïve FL patients with high tumor burden received six cycles of atezolizumab 1200 mg and obinutuzumab 1000 mg (O + A) intravenously every 21 days as induction treatment. Patients also received positron emission tomography (PET)-adapted ultra-low dose radiotherapy (RT; 4Gy) to all PET-avid sites after cycle 2, followed by two years of obinutuzumab maintenance. Only patients who had residual lymphadenopathy >1 cm at PET2 assessment were treated with RT to minimise toxicity in O + A early responders.
This treatment regimen was intended to exploit the known immunostimulatory and cytotoxic properties of the combination of checkpoint inhibition (atezolizumab) and obinutuzumab (with its additional antibody-dependent cellular cytotoxicity activity) together with RT for enhanced disease control, according to the investigators.
The primary endpoint of complete response (CR) was achieved in 93% of patients, with an objective response rate of 100%. With 41-month median follow-up, three-year progression-free survival was 80% and overall survival was 100%. Grade 3–4 adverse events occurred in 31% of patients (two immune-related), which the researchers described as “an encouragingly low toxicity profile.”
The researchers noted that these results compare favorably to those of front-line chemoimmunotherapy regimens, where CR rates are up to 80% and reported grade 3–4 toxicity is 70%–75%.
“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,” the authors wrote.
The researchers added that early indications from their translational substudies suggest that PET radiomics and immune gene analyses provide promise as biomarkers for response in immunotherapy combinations.
