Long-Term Efficacy and Safety of Lifileucel Tumor-Infiltrating Lymphocyte Cell Therapy in Patients With Advanced Melanoma: A 5-Year Analysis of the C-144-01 Study

T Theresa Medina (From the Sandra and Edward Meyer Cancer Center (J.D.W.) and the Department of Medicine (J.D.W., M.A.P.), Weill Cornell Medicine, and Memorial Sloan Kettering Cancer Center (M.A.P.) — both in New York; Istituto Oncologico Veneto, IRCCS, Padua (V.C.-S.), European Institute of Oncology, IRCCS, Milan (P.Q.), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola (M.G.), University of Siena and the Center for Immuno-Oncology, University Hospital of Siena, Siena (M.M.), and Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples (P.A.A.) — all in Italy; Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland (P.R.); Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.); University Hospital Essen, the German Cancer Consortium, the National Center for Tumor Diseases–West, the Research Alliance Ruhr, Research Center One Health, and University Duisburg-Essen — all in Essen, Germany (D.S.); the College of Medicine, Swansea University, Swansea (J.W.), Brist...) J Jason A. Chesney (James Graham Brown Cancer Center, University of Louisville, Louisville, KY) H Harriet M. Kluger O Omid Hamid (5The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate, Translational Research & ImmunoOncolgy, Los Angeles, United States) E Eric D. Whitman (Atlantic Health System, Morristown, NJ) M Mike Cusnir (1Mount Sinai Medical Center, Hematology Oncology, Miami Beach, United States) S Sajeve S. Thomas (AdventHealth Orlando, Orlando, FL) M Martin Wermke (National Center for Tumor Diseases–University Cancer Center Early Clinical Trial Unit, Technische Universität Dresden, Dresden, Germany) E Evidio Domingo-Musibay (Allina Health Cancer Institute, Minneapolis, MN) G Giao Q. Phan (UConn Health/Neag Cancer Center, Farmington, CT) J John M. Kirkwood J James Larkin J Jeffrey Weber (Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY) F Friedrich Graf Finckenstein (Iovance Biotherapeutics, Inc, San Carlos, CA) J Jeffrey Chou (Iovance Biotherapeutics, Inc, San Carlos, CA) B Brian Gastman (The Cleveland Clinic Foundation, Cleveland, OH) X Xiao Wu R Rana Fiaz (Iovance Biotherapeutics, Inc, San Carlos, CA) A Amod A. Sarnaik (H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL) B Brendan Curti K Kevin Kim (Occidental College) G Gregory Daniels M Melissa Wilson S Sylvia Lee (Colorado State University, Fort Collins, Colorado, United States) I Igor Puzanov A Amy Harker-Murray T Theodore Logan J Jan Christoph Simon I Ioannis Thomas B Beatrice Schuler-Thurner R Rose Moritz J Jessica Hassel G Gotz Ulrich Grigoliet A Ana Arance (Hospital Clinic Barcelona and IDIBAPS, Barcelona, Spain) B Belen Rubio J Juan Rodriguez A Alfonso Berrocal M Miguel de Sanmamed H Hendrik-Tobias Arkenau (Ellipses Pharma, London, United Kingdom) T Thomas Evans P Pippa Corrie S Stéphane Dalle C Christoph Bedane J Judit Oláh A Angela Orcurto

Abstract

Patients with advanced melanoma resistant to immune checkpoint or BRAF/MEK inhibitors have treatment options with relatively low efficacy. Lifileucel, a one-time autologous tumor-infiltrating lymphocyte cell therapy, was approved in the United States on the basis of the pivotal C-144-01 study. A 5-year follow-up of the C-144-01 trial assessed the long-term efficacy and safety of lifileucel. At the cutoff date (November 20, 2024), the objective response rate was 31.4% (complete response [CR], 5.9%; partial response [PR], 25.5%). Overall, 79.3% of patients had tumor burden reduction; 16 had deepened responses with four converting from PR to CR > 1 year after lifileucel infusion; 31.3% of responders completed the 5-year assessment with ongoing responses. The median duration of response was 36.5 months. Responders (n = 48) had lower tumor burden and fewer liver or brain metastases than the overall population. The median overall survival (OS) was 13.9 months, with a 5-year OS of 19.7%. Adverse events were consistent with nonmyeloablative lymphodepletion and interleukin-2 safety profiles and declined rapidly within 2 weeks after lifileucel infusion. Most grade 3/4 cytopenias resolved to grade ≤2 by day 30. This 5-year analysis demonstrated long-term benefit and meaningful OS with one-time lifileucel therapy, with no additional long-term safety concerns.

Article Details

Volume / Issue Vol. 43, Issue 33
Published November 20, 2025
Pages 3565-3572
ISSN 0732-183X
Publisher Lippincott Williams & Wilkins

Journal Info

Journal of Clinical Oncology

Lippincott Williams & Wilkins

ISSN: 0732-183X Health Sciences

Authors (45)

T

Theresa Medina

From the Sandra and Edward Meyer Cancer Center (J.D.W.) and the Department of Medicine (J.D.W., M.A.P.), Weill Cornell Medicine, and Memorial Sloan Kettering Cancer Center (M.A.P.) — both in New York; Istituto Oncologico Veneto, IRCCS, Padua (V.C.-S.), European Institute of Oncology, IRCCS, Milan (P.Q.), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola (M.G.), University of Siena and the Center for Immuno-Oncology, University Hospital of Siena, Siena (M.M.), and Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples (P.A.A.) — all in Italy; Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland (P.R.); Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.); University Hospital Essen, the German Cancer Consortium, the National Center for Tumor Diseases–West, the Research Alliance Ruhr, Research Center One Health, and University Duisburg-Essen — all in Essen, Germany (D.S.); the College of Medicine, Swansea University, Swansea (J.W.), Brist...

J

Jason A. Chesney

James Graham Brown Cancer Center, University of Louisville, Louisville, KY

H

Harriet M. Kluger

O

Omid Hamid

5The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate, Translational Research & ImmunoOncolgy, Los Angeles, United States

E

Eric D. Whitman

Atlantic Health System, Morristown, NJ

M

Mike Cusnir

1Mount Sinai Medical Center, Hematology Oncology, Miami Beach, United States

S

Sajeve S. Thomas

AdventHealth Orlando, Orlando, FL

M

Martin Wermke

National Center for Tumor Diseases–University Cancer Center Early Clinical Trial Unit, Technische Universität Dresden, Dresden, Germany

E

Evidio Domingo-Musibay

Allina Health Cancer Institute, Minneapolis, MN

G

Giao Q. Phan

UConn Health/Neag Cancer Center, Farmington, CT

J

John M. Kirkwood

J

James Larkin

J

Jeffrey Weber

Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY

F

Friedrich Graf Finckenstein

Iovance Biotherapeutics, Inc, San Carlos, CA

J

Jeffrey Chou

Iovance Biotherapeutics, Inc, San Carlos, CA

B

Brian Gastman

The Cleveland Clinic Foundation, Cleveland, OH

X

Xiao Wu

R

Rana Fiaz

Iovance Biotherapeutics, Inc, San Carlos, CA

A

Amod A. Sarnaik

H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL

B

Brendan Curti

K

Kevin Kim

Occidental College

G

Gregory Daniels

M

Melissa Wilson

S

Sylvia Lee

Colorado State University, Fort Collins, Colorado, United States

I

Igor Puzanov

A

Amy Harker-Murray

T

Theodore Logan

J

Jan Christoph Simon

I

Ioannis Thomas

B

Beatrice Schuler-Thurner

R

Rose Moritz

J

Jessica Hassel

G

Gotz Ulrich Grigoliet

A

Ana Arance

Hospital Clinic Barcelona and IDIBAPS, Barcelona, Spain

B

Belen Rubio

J

Juan Rodriguez

A

Alfonso Berrocal

M

Miguel de Sanmamed

H

Hendrik-Tobias Arkenau

Ellipses Pharma, London, United Kingdom

T

Thomas Evans

P

Pippa Corrie

S

Stéphane Dalle

C

Christoph Bedane

J

Judit Oláh

A

Angela Orcurto