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Immune checkpoint inhibitor therapy after tumor-infiltrating lymphocytes in unresectable melanoma.

James William Smithy ,
Allison Betof ,
Sebastian Klobuch ,
Troels Holz Borch ,
Hannah L Kalvin ,
Nitzan Hasson ,
Shirly Grynberg ,
Rodabe Amaria ,
Juliane A Czapla ,
Megan D Schollenberger ,
Andrew J S Furness ,
Jessica C Hassel ,
Martin Wermke ,
Sidsel Pedersen ,
Inge Marie Svane ,
Antonio Ocejo ,
Elizabeth Buchbinder ,
Douglas B Johnson ,
Michael Postow ,
Cristy Los ,
Jose Lutzky ,
Evan J Lipson ,
Ryan J Sullivan ,
Harriet M Kluger ,
Katherine S Panageas ,
Marco Donia ,
John B A G Haanen ,
Alexander Noor Shoushtari

Abstract

PATIENTS AND METHODS

Patients with unresectable melanoma who received ICI therapy both before and after TIL treatment were retrospectively identified at 14 international centers. Safety was evaluated among all patients that received one dose of ICI therapy after TIL. Objective response rates (ORR) were determined based on investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 responses based on radiology reports. Kaplan-Meier methodology was used to estimate overall survival (OS) and melanoma-specific survival.

CONCLUSION

Efficacy with ICI after TIL was limited, with no evidence of synergistic toxicity. As TIL therapy becomes more widely available, these data highlight the need for novel therapies in this setting and support the inclusion of this population in future clinical trials.

RESULTS

Among 133 patients assessed for response to ICI therapy after progression on TIL therapy, the ORR was 11% (n=14; 95% CI 5.9% to 17%), including 3 complete responses (2.3%) and 11 partial responses (8.3%). Among patients treated with a programmed death-1 inhibitor prior to TIL (n=121), the ORR was 8.3% (95% CI 4.0% to 15%). At a median follow-up among survivors of 21 months, median OS from post-TIL ICI was 8.8 months (95% CI 6.5 to 12 months). Among 14 patients with response to post-TIL ICI, 13 received an ICI they had not previously received. In the safety cohort (n=138), post-TIL ICI therapy-related toxicity occurred in 31 patients(22%), among which 7 patients (5.1%) experienced recurrence of an adverse event experienced with prior ICI treatment.

PURPOSE

Treatment strategies for patients with advanced melanoma resistant to adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) remain undefined. The efficacy of immune checkpoint inhibitors (ICIs) after TIL has not been previously described.

More about this publication

Journal for immunotherapy of cancer

Volume 14
Issue nr. 6
Publication date 25-06-2026

Full text links

Publisher website (DOI) 10.1136/jitc-2026-015360
Europe PubMed Central 42350045
Pubmed 42350045

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