Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study
Background Patients with advanced melanoma have limited treatment options after progression on immune checkpoint inhibitors (ICI). Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% in 66 pati...
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BMJ Publishing Group
2022-12-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/10/12/e005755.full |
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| author | Jessica C Hassel James Larkin Madan Jagasia Harriet Kluger Omid Hamid Jeffrey Weber Jason Chesney Amod Sarnaik John M Kirkwood Eric Whitman Martin Wermke Evidio Domingo-Musibay Theresa Medina Sajeve Thomas Wen Shi Xiao Wu Nikhil I Khushalani Parameswaran Hari Marlana Orloff Mike Cusnir Giao Q Phan Andrew J S Furness Michael E Egger Friedrich Graf Finckenstein Giri Sulur |
| author_facet | Jessica C Hassel James Larkin Madan Jagasia Harriet Kluger Omid Hamid Jeffrey Weber Jason Chesney Amod Sarnaik John M Kirkwood Eric Whitman Martin Wermke Evidio Domingo-Musibay Theresa Medina Sajeve Thomas Wen Shi Xiao Wu Nikhil I Khushalani Parameswaran Hari Marlana Orloff Mike Cusnir Giao Q Phan Andrew J S Furness Michael E Egger Friedrich Graf Finckenstein Giri Sulur |
| author_sort | Jessica C Hassel |
| collection | DOAJ |
| description | Background Patients with advanced melanoma have limited treatment options after progression on immune checkpoint inhibitors (ICI). Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% in 66 patients who progressed after ICI and targeted therapy. Herein, we report independent review committee (IRC)-assessed outcomes of 153 patients treated with lifileucel in a large multicenter Phase 2 cell therapy trial in melanoma.Methods Eligible patients had advanced melanoma that progressed after ICI and targeted therapy, where appropriate. Melanoma lesions were resected (resected tumor diameter ≥1.5 cm) and shipped to a central good manufacturing practice facility for 22-day lifileucel manufacturing. Patients received a non-myeloablative lymphodepletion regimen, a single lifileucel infusion, and up to six doses of high-dose interleukin-2. The primary endpoint was IRC-assessed ORR (Response Evaluation Criteria in Solid Tumors V.1.1).Results The Full Analysis Set consisted of 153 patients treated with lifileucel, including longer-term follow-up on the 66 patients previously reported. Patients had received a median of 3.0 lines of prior therapy (81.7% received both anti-programmed cell death protein 1 and anti-cytotoxic lymphocyte-associated protein 4) and had high disease burden at baseline (median target lesion sum of diameters (SOD): 97.8 mm; lactate dehydrogenase (LDH) >upper limit of normal: 54.2%). ORR was 31.4% (95% CI: 24.1% to 39.4%), with 8 complete responses and 40 partial responses. Median duration of response was not reached at a median study follow-up of 27.6 months, with 41.7% of the responses maintained for ≥18 months. Median overall survival and progression-free survival were 13.9 and 4.1 months, respectively. Multivariable analyses adjusted for Eastern Cooperative Oncology Group performance status demonstrated that elevated LDH and target lesion SOD >median were independently correlated with ORR (p=0.008); patients with normal LDH and SOD <median had greater likelihood of response than those with either (OR=2.08) or both (OR=4.42) risk factors. The most common grade 3/4 treatment-emergent adverse events (≥30%) were thrombocytopenia (76.9%), anemia (50.0%), and febrile neutropenia (41.7%).Conclusions Investigational lifileucel demonstrated clinically meaningful activity in heavily pretreated patients with advanced melanoma and high tumor burden. Durable responses and a favorable safety profile support the potential benefit of one-time lifileucel TIL cell therapy in patients with limited treatment options in ICI-refractory disease. |
| format | Article |
| id | doaj-art-900e2415861b4b7ead600bdf8b2b9e19 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-900e2415861b4b7ead600bdf8b2b9e192025-08-20T02:32:59ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262022-12-01101210.1136/jitc-2022-005755Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 studyJessica C Hassel0James Larkin1Madan Jagasia2Harriet Kluger3Omid Hamid4Jeffrey Weber5Jason Chesney6Amod Sarnaik7John M Kirkwood8Eric Whitman9Martin Wermke10Evidio Domingo-Musibay11Theresa Medina12Sajeve Thomas13Wen Shi14Xiao Wu15Nikhil I Khushalani16Parameswaran Hari17Marlana Orloff18Mike Cusnir19Giao Q Phan20Andrew J S Furness21Michael E Egger22Friedrich Graf Finckenstein23Giri Sulur24University Hospital Heidelberg, Heidelberg, GermanyHRB Centre for Primary Care Research, Royal College of Surgeons in Ireland, Dublin, Ireland3 Vanderbilt University Medical Center, Nashville, Tennessee, USA1Yale University, School of Medicine, New Haven, CT, USAThe Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, California, USA24 Perlmutter Cancer Center, NYU Langone Health, New York, New York, USA5 James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, USA10 H Lee Moffitt Canc Ctr, Tampa, Florida, USA19 Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USAAtlantic Health System Cancer Care, Morristown, New Jersey, USADepartment of Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany5University of Minnesota Medical Center, Minneapolis, MN, USA9University of Colorado, Aurora, CO, USAMD Anderson Cancer Center Orlando, Orlando, Florida, USAIovance Biotherapeutics Inc, San Carlos, California, USADepartment of Biostatistics, Harvard University T H Chan School of Public Health, Boston, MA, USADepartment of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida, USAMedicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA14Thomas Jefferson University Hospital, Philadelphia, PA, USADivision of Hematology & Oncology, Mount Sinai Medical Center, Miami Beach, Florida, USASurgery, Virginia Commonwealth University, Massey Cancer Center, Richmond, Virginia, USAThe Royal Marsden NHS Foundation Trust, London, UKDepartment of Medicine, University of Louisville, Louisville, Kentucky, USAIovance Biotherapeutics Inc, San Carlos, California, USAIovance Biotherapeutics Inc, San Carlos, California, USABackground Patients with advanced melanoma have limited treatment options after progression on immune checkpoint inhibitors (ICI). Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% in 66 patients who progressed after ICI and targeted therapy. Herein, we report independent review committee (IRC)-assessed outcomes of 153 patients treated with lifileucel in a large multicenter Phase 2 cell therapy trial in melanoma.Methods Eligible patients had advanced melanoma that progressed after ICI and targeted therapy, where appropriate. Melanoma lesions were resected (resected tumor diameter ≥1.5 cm) and shipped to a central good manufacturing practice facility for 22-day lifileucel manufacturing. Patients received a non-myeloablative lymphodepletion regimen, a single lifileucel infusion, and up to six doses of high-dose interleukin-2. The primary endpoint was IRC-assessed ORR (Response Evaluation Criteria in Solid Tumors V.1.1).Results The Full Analysis Set consisted of 153 patients treated with lifileucel, including longer-term follow-up on the 66 patients previously reported. Patients had received a median of 3.0 lines of prior therapy (81.7% received both anti-programmed cell death protein 1 and anti-cytotoxic lymphocyte-associated protein 4) and had high disease burden at baseline (median target lesion sum of diameters (SOD): 97.8 mm; lactate dehydrogenase (LDH) >upper limit of normal: 54.2%). ORR was 31.4% (95% CI: 24.1% to 39.4%), with 8 complete responses and 40 partial responses. Median duration of response was not reached at a median study follow-up of 27.6 months, with 41.7% of the responses maintained for ≥18 months. Median overall survival and progression-free survival were 13.9 and 4.1 months, respectively. Multivariable analyses adjusted for Eastern Cooperative Oncology Group performance status demonstrated that elevated LDH and target lesion SOD >median were independently correlated with ORR (p=0.008); patients with normal LDH and SOD <median had greater likelihood of response than those with either (OR=2.08) or both (OR=4.42) risk factors. The most common grade 3/4 treatment-emergent adverse events (≥30%) were thrombocytopenia (76.9%), anemia (50.0%), and febrile neutropenia (41.7%).Conclusions Investigational lifileucel demonstrated clinically meaningful activity in heavily pretreated patients with advanced melanoma and high tumor burden. Durable responses and a favorable safety profile support the potential benefit of one-time lifileucel TIL cell therapy in patients with limited treatment options in ICI-refractory disease.https://jitc.bmj.com/content/10/12/e005755.full |
| spellingShingle | Jessica C Hassel James Larkin Madan Jagasia Harriet Kluger Omid Hamid Jeffrey Weber Jason Chesney Amod Sarnaik John M Kirkwood Eric Whitman Martin Wermke Evidio Domingo-Musibay Theresa Medina Sajeve Thomas Wen Shi Xiao Wu Nikhil I Khushalani Parameswaran Hari Marlana Orloff Mike Cusnir Giao Q Phan Andrew J S Furness Michael E Egger Friedrich Graf Finckenstein Giri Sulur Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study Journal for ImmunoTherapy of Cancer |
| title | Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study |
| title_full | Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study |
| title_fullStr | Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study |
| title_full_unstemmed | Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study |
| title_short | Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study |
| title_sort | efficacy and safety of lifileucel a one time autologous tumor infiltrating lymphocyte til cell therapy in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies pooled analysis of consecutive cohorts of the c 144 01 study |
| url | https://jitc.bmj.com/content/10/12/e005755.full |
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