Lung cancer (Amsterdam, Netherlands) · 2022
Image-guided interventional radiological delivery of chimeric antigen receptor (CAR) T cells for pleural malignancies in a phase I/II clinical trial.
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Ghosn Mario, Cheema Waseem, Zhu Amy, Livschitz Jennifer, Maybody Majid, Boas Franz E, Santos Ernesto, Kim DaeHee, Beattie Jason A, Offin Michael, Rusch Valerie W, Zauderer Marjorie G, Adusumilli Prasad S, Solomon Stephen B
Аннотация
OBJECTIVES: We describe techniques and results of image-guided delivery of mesothelin-targeted chimeric antigen receptor (CAR) T cells in patients with pleural malignancies in a phase I/II trial (ClinicalTrials.gov: NCT02414269).
MATERIALS AND METHODS: Patients without a pleural catheter or who lack effusion for insertion of a catheter (31 of 41) were administered intrapleural CAR T cells by interventional radiologists under image guidance by computed tomography or ultrasound. CAR T cells were administered through a needle in an accessible pleural loculation (intracavitary) or following an induced loculated artificial pneumothorax. In patients where intracavitary infusion was not feasible, CAR T cells were injected via percutaneous approach either surrounding and/or in the pleural nodule/thickening (intratumoral). Pre- and post-procedural clinical, laboratory, and imaging findings were assessed.
RESULTS: CAR T cells were administered intrapleurally in 31 patients (33 procedures, 2 patients were administered a second dose) with successful delivery of planned dose (10-186 mL); 14/33 (42%) intracavitary and 19/33 (58%) intratumoral. All procedures were completed within 2 h of T-cell thawing. There were no procedure-related adverse events greater than grade 1 (1 in 3 patients had prior ipsilateral pleural fusion procedures). The most common imaging finding was ground glass opacities with interlobular septal thickening and/or consolidation, observed in 12/33 (36%) procedures. There was no difference in the incidence of fever, CRP, IL-6, and peak vector copy number in the peripheral blood between infusion methods.
CONCLUSION: Image-guided intrapleural delivery of CAR T cells using intracavitary or intratumoral routes is feasible, repeatable and safe across anatomically variable pleural cancers.
MATERIALS AND METHODS: Patients without a pleural catheter or who lack effusion for insertion of a catheter (31 of 41) were administered intrapleural CAR T cells by interventional radiologists under image guidance by computed tomography or ultrasound. CAR T cells were administered through a needle in an accessible pleural loculation (intracavitary) or following an induced loculated artificial pneumothorax. In patients where intracavitary infusion was not feasible, CAR T cells were injected via percutaneous approach either surrounding and/or in the pleural nodule/thickening (intratumoral). Pre- and post-procedural clinical, laboratory, and imaging findings were assessed.
RESULTS: CAR T cells were administered intrapleurally in 31 patients (33 procedures, 2 patients were administered a second dose) with successful delivery of planned dose (10-186 mL); 14/33 (42%) intracavitary and 19/33 (58%) intratumoral. All procedures were completed within 2 h of T-cell thawing. There were no procedure-related adverse events greater than grade 1 (1 in 3 patients had prior ipsilateral pleural fusion procedures). The most common imaging finding was ground glass opacities with interlobular septal thickening and/or consolidation, observed in 12/33 (36%) procedures. There was no difference in the incidence of fever, CRP, IL-6, and peak vector copy number in the peripheral blood between infusion methods.
CONCLUSION: Image-guided intrapleural delivery of CAR T cells using intracavitary or intratumoral routes is feasible, repeatable and safe across anatomically variable pleural cancers.