66MO - Early complete metabolic response predicts long-term efficacy after adoptive cell therapy using tumor-infiltrating lymphocytes

Background

Recently, adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) showed superior progression-free survival compared to ipilimumab monotherapy in patients with advanced melanoma. Previous reports have shown impressive durability of complete responses (CR) after TIL therapy, however CRs can develop over a long time. In this study we investigated whether early metabolic response adds prognostic information to conventional computed tomography (CT) scans.

Methods

A total of 44 patients were treated with TIL therapy at the National Center for Cancer Immune Therapy, Denmark, between July 2011 and May 2018 (NCT00937625, NCT02379195 and NCT02354690). [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography-CT (FDG-PET/CT) scans were performed before therapy, 6-8 weeks post TIL infusion, and 12-16 weeks post TIL infusion. Radiologic responses were assessed according to RECIST 1.1 and metabolic responses according to PERCIST. Survival estimates were calculated using the Kaplan-Meier method. All patients were followed for a minimum of 5 years.

Results

Within the first two follow-up scans, only one patient achieved a CR, but seven patients achieved complete metabolic response (CMR). In addition, partial responses (PR) were observed in 14 patients and partial metabolic responses (PMR) in 6 patients. All patients with CMR, except one whose death was not related to melanoma, were still alive and 71% (5 of 7 patients) were progression-free after >5 years (with a median follow-up time of 108 months). Patients who achieved PR was subcategorized into patients with PMR and CMR. Patients with PR/PMR (5 patients) had a median progression-free survival (mPFS) of 9.1 months whereas mPFS in patients with PR/CMR (6 patients) was not reached.

Conclusions

Early CMR on FDG-PET/CT scans is a strong predictor of long-term survival after TIL therapy in melanoma. Further, FDG-PET/CT scans appears superior to CT scans for early prognostic information after TIL therapy in melanoma. FDG-PET/CT scans can be used to tailor patient-specific management and follow-up strategies.

Clinical trial identification

NCT00937625, NCT02379195 and NCT02354690.

Legal entity responsible for the study

I-M. Svane.

Funding

Has not received any funding.

Disclosure

I. Svane: Financial Interests, Personal, Advisory Board: BMS, Pierre Fabre, Novartis; Financial Interests, Personal, Invited Speaker: MSD, Pierre Fabre, Novartis, Roche, BMS; Financial Interests, Personal, Writing Engagement: MSD; Financial Interests, Personal, Stocks/Shares, Cofounder and Founder warrents: IO Biotech; Financial Interests, Institutional, Research Grant: Adaptimmune, Enara Bio, Lytix Biopharma, TILT Biotherapeutics; Financial Interests, Institutional, Funding: Evaxion; Non-Financial Interests, Personal, Principal Investigator: BMS, Roche, TILT Biotherapeutics, Lytix Biopharma, Novartis. E. Ellebæk: Financial Interests, Personal, Invited Speaker: Pierre Fabre, BMS, Novartis, MSD, Pfizer; Other, Personal, Other, Travel and conference expenses: MSD, Pierre Fabre. T.H. Borch: Other, Personal, Other, Speaker's honoraria: Bristol Myers-Squibb. All other authors have declared no conflicts of interest.