接受 CAR-T 治疗的淋巴瘤患者的缺氧特异性成像

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.

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.

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.

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.