Questions Remain About Role of Hypoxia Related to NHL CAR T-cell Therapy

Intratumoral hypoxia may be associated with chimeric antigen receptor (CAR) T-cell therapy outcomes in patients with non-Hodgkin lymphoma (NHL), according to data from a pilot study.

Divita Pandita, MBA, of the University of California San Francisco, and colleagues presented the results of a single-center study that evaluated ¹⁸F-fluoroazomycin arabinoside (FAZA) PET scans before CAR T-cell therapy and assessed associations between intratumoral hypoxia and post-CAR T-cell therapy outcomes (ABCL-323) during the Eleventh Annual Meeting of the Society of Hematologic Oncology.

The enrolled patients received a one-time FAZA PET scan between their initial evaluation and lymphodepletion. Intratumoral hypoxia was defined as a tumor/muscle ratio of ≥1.20. The researchers planned to enroll 30 patients, with an interim futility analysis after 16 patients.

Sixteen patients with NHL underwent FAZA PET at a median of 16 days prior to CAR T-cell therapy. Three of these patients had no evidence of disease prior to CAR T-cell therapy.

FAZA uptake was relatively uncommon, the researchers noted, potentially be due to scan timing or bridging therapy.

Six patients had FAZA uptake higher than that of baseline levels. Using the defined cutoff, only one patient had intratumoral hypoxia in a solitary extranodal lesion. The researchers noted that this patient was also the only patient with progressive disease at day 90+ after undergoing CAR T-cell therapy infusion.

Of the five other patients with FAZA uptake greater than baseline, one had partial response at day 30+ infusion and four had complete responses.

“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,” the researchers wrote.

Reference

Pandita D, Banerjee R, Wang V, et al. Hypoxia-Specific Imaging Before CAR-T Therapy in Relapsed and Refractory B-Cell Non-Hodgkin Lymphoma. Abstract ABCL-323. Presented at the Eleventh Annual Meeting of the Society of Hematologic Oncology; September 6-9, 2023; Houston, Texas.