T-cell dysregulation informs radiotherapy-immunotherapy response in B-cell lymphoma: results from a Phase I trial
- Author(s)
- Hawkes, EA; Palmer, J; Khor, R; Lee, ST; Burgess, M; Law, SC; Gandhi, MK; Chong, G; Shortt, J; Chowdhury, R; Swain, F; Churilov, L; MacManus, MM; Smith, C; Scott, FE; Martynchyk, A; Barraclough, A; Manos, K; Scott, AM; Keane, C;
- Journal Title
- Blood Advances
- Publication Type
- Online publication before print
- Abstract
- Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are highly radiosensitive with immune-driven abscopal responses reported. PD-1/PD-L1 inhibitors are relatively ineffective in DLBCL/FL but evidence suggests synergy with radiotherapy (RT), yet no clear biomarkers. This phase I study (NCT03610061) examined safety of escalating RT dose and treated volumes with durvalumab (PD-L1i) in thirty-four adult relapsed/refractory (RR)DLBCL and RRFL and the role of immune-cell subsets on outcomes. Patients received external-beam RT (2.5-30 Gray [Gy], five or ten fractions upto 3 target sites) plus durvalumab from RT day two, until progression. Novel Positron Emission Tomography (PET) biodistribution studies of 89Zr-durvalumab and CD8 T-cell minibody-89Zr-Df-cremirlimab were incorporated. RT recommended phase II dose was 10 Gy/5 fractions and 30 Gy/10 fractions to 3 sites for FL and DLBCL respectively. Most common Grade 3-4 toxicities included anaemia (9%), neutropenia (11%), liver dysfunction (5%). Overall response was 60% in FL (3/5; Complete Response [CR] 40% [2/5]), and 14% in DLBCL (4/27; CR 7% (2/27) Distinct peripheral blood and tumour T cell features, including CD8-PET-determined intratumoral CD8 T cells, correlated with response (p<0.05) RT-Durvalumab with 30Gy/10 fractions of radiotherapy to three disease sites is safe and offers promising responses in FL. Intratumoural and peripheral blood CD8 T cell dysregulation correlate with treatment response.
- Department(s)
- Radiation Oncology
- Publisher's Version
- https://doi.org/10.1182/bloodadvances.2025016505
- Open Access at Publisher's Site
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Creation Date: 2025-07-29 05:57:09
Last Modified: 2025-07-29 05:57:27