Hypoxia-specific imaging in patients with lymphoma undergoing CAR-T therapy.

Purpose: Intratumoral hypoxia in non-Hodgkin's Lymphoma (NHL) may interfere with chimeric antigen receptor T-cell (CAR-T) function. We conducted a single-center pilot study (clinicaltrials.gov ID NCT04409314) of [ ¹⁸ F]fluoroazomycin arabinoside, a hypoxia-specific radiotracer abbreviated as [ ¹⁸ F]FAZA, to assess the feasibility of this positron emission tomography (PET) imaging modality in this population.
Methods: Patients with relapsed NHL being evaluated for CAR-T therapy received a one-time [ ¹⁸ F]FAZA PET scan before pre-CAR-T lymphodepletion. A tumor to mediastinum (T/M) ratio of 1.2 or higher with regard to [ ¹⁸ F]FAZA uptake was defined as positive for intratumoral hypoxia. We planned to enroll 30 patients with an interim futility analysis after 16 scans.
Results: Of 16 scanned patients, 3 had no evidence of disease by standard [ ¹⁸ F]fluorodeoxyglucose PET imaging before CAR-T therapy. Six patients (38%) had any [ ¹⁸ F]FAZA uptake above background. Using a T/M cutoff of 1.20, only one patient (a 68-year-old male with relapsed diffuse large B-cell lymphoma) demonstrated intratumoral hypoxia in an extranodal chest wall lesion (T/M 1.35). Interestingly, of all 16 scanned patients, he was the only patient with progressive disease within 1 month of CAR-T therapy. However, because of our low overall proportion of positive scans, our study was stopped for futility.
Conclusions: Our pilot study identified low-level [ ¹⁸ F]FAZA uptake in a small number of patients with NHL receiving CAR-T therapy. The only patient who met our pre-specified threshold for intratumoral hypoxia was also the only patient with early CAR-T failure. Future plans include exploration of [ ¹⁸ F]FAZA in a more selected patient population.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)