ABCL-323 Hypoxia-Specific Imaging Before CAR-T Therapy in Relapsed and Refractory B-Cell Non-Hodgkin Lymphoma

• Published in: Clinical lymphoma, myeloma and leukemia Vol. 23; pp. S429 - S430
• Main Authors: Pandita, Divita, Banerjee, Rahul, Wang, Victoria, Huang, Chiung-Yu, Leonard, Michelle, Larue, Siobhan, Ahmadi, Michael, Kaplan, Lawrence, Ai, Weiyun, Fakhri, Bita, Spinner, Michael, Seshadri, Madhav, Pampaloni, Miguel, Andreadis, Charalambos
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2023
• Subjects: CAR-T; FAZA; hypoxia; lymphoma; PET; hypoxia; FAZA; CAR-T; PET; lymphoma
• ISSN: 2152-2650; 2152-2669
• DOI: 10.1016/S2152-2650(23)01314-9

Hypoxia may interfere with immune effector cell activation and function, including CAR-T therapy outcomes in non-Hodgkin lymphoma (NHL). 18F-fluoroazomycin arabinoside (FAZA) is a hypoxia-specific PET radiotracer with demonstrated applications in solid tumors. We conducted a single-center pilot study evaluating FAZA PET scans before CAR-T therapy to assess the feasibility of this imaging modality and to explore associations between intratumoral hypoxia and post-CAR-T outcomes. Enrolled patients received a one-time FAZA PET scan between initial evaluation and lymphodepletion, with a tumor/muscle (T/M) ratio of ≥1.20 as the threshold for intratumoral hypoxia based on prior studies. We planned to enroll 30 patients using Simon two-stage minimax design, with an interim futility analysis after 16 patients and study closure if 6 or fewer scans were positive for intratumoral hypoxia. Patients with NHL being evaluated for CD19-directed CAR-T therapy at UCSF. 16 patients, (14 DLBCL, 1 mantle cell lymphoma, 1 follicular lymphoma), underwent FAZA PET scans a median of 16 days prior to CAR-T therapy (range 7-70 days). Of note, 3 patients had no evidence of disease by FDG imaging before CAR-T. In all, 6 patients had FAZA uptake higher than that of baseline muscle. Using the T/M cutoff of 1.20, only 1 patient (68yoM with DLBCL) demonstrated intratumoral hypoxia in a solitary extranodal lesion (SUVmax 2.12, T/M 1.35). Notably, this was also the only patient with PD at Day +90 after liso-cel. Of the remaining 5 patients with FAZA uptake above baseline, one patient had a Day +30 PR and the remaining had CRs. Our pilot study of 16 patients with B-cell NHL identified low-level FAZA uptake in 38% of our scanned patients. Only 1 patient met our pre-specified threshold for positive intratumoral hypoxia and was also the only scanned patient with Day +90 PD. FAZA uptake was relatively uncommon in unselected patients with NHL in our study, potentially due to scan timing and pre-CAR-T bridging. Future plans include exploration of FAZA in a more selected patient population, e.g. elevated LDH, high metabolic tumor burden by FDG PET, or previous failure of other immunotherapies.