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Efficacy of adoptive therapy with tumor-infiltrating lymphocytes and recombinant interleukin-2 in advanced cutaneous melanoma: a systematic review and meta-analysis.
Dafni, U; Michielin, O; Lluesma, S Martin; Tsourti, Z; Polydoropoulou, V; Karlis, D; Besser, M J; Haanen, J; Svane, I-M; Ohashi, P S; Kammula, U S; Orcurto, A; Zimmermann, S; Trueb, L; Klebanoff, C A; Lotze, M T; Kandalaft, L E; Coukos, G.
Afiliação
  • Dafni U; Department of Oncology, CHUV, University of Lausanne, Lausanne, Switzerland; Faculty of Nursing, National and Kapodistrian University of Athens, Athens, Greece.
  • Michielin O; Department of Oncology, CHUV, University of Lausanne, Lausanne, Switzerland.
  • Lluesma SM; Department of Oncology, CHUV, University of Lausanne, Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.
  • Tsourti Z; Scientific Research Consulting Hellas, Statistics Center, Athens.
  • Polydoropoulou V; Scientific Research Consulting Hellas, Statistics Center, Athens.
  • Karlis D; Department of Statistics, Athens University of Economics and Business, Athens, Greece.
  • Besser MJ; Ella Institute for the Treatment and Research of Melanoma and Skin Cancer, Sheba Medical Center, Tel Aviv; Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Haanen J; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Svane IM; Department of Hematology and Oncology, Center for Cancer Immune Therapy, Herlev Hospital, Herlev, Denmark.
  • Ohashi PS; Department of Immunology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
  • Kammula US; Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh.
  • Orcurto A; Department of Oncology, CHUV, University of Lausanne, Lausanne, Switzerland.
  • Zimmermann S; Department of Oncology, CHUV, University of Lausanne, Lausanne, Switzerland.
  • Trueb L; Department of Oncology, CHUV, University of Lausanne, Lausanne, Switzerland.
  • Klebanoff CA; Center for Cell Engineering and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York; Parker Institute for Cancer Immunotherapy, New York; Weill Cornell Medical College, New York.
  • Lotze MT; Department of Immunology, University of Pittsburgh Schools of the Health Sciences, Pittsburgh, USA.
  • Kandalaft LE; Department of Oncology, CHUV, University of Lausanne, Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.
  • Coukos G; Department of Oncology, CHUV, University of Lausanne, Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland. Electronic address: george.coukos@chuv.ch.
Ann Oncol ; 30(12): 1902-1913, 2019 12 01.
Article em En | MEDLINE | ID: mdl-31566658
ABSTRACT
Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) has been tested in advanced melanoma patients at various centers. We conducted a systematic review and meta-analysis to assess its efficacy on previously treated advanced metastatic cutaneous melanoma. The PubMed electronic database was searched from inception to 17 December 2018 to identify studies administering TIL-ACT and recombinant interleukin-2 (IL-2) following non-myeloablative chemotherapy in previously treated metastatic melanoma patients. Objective response rate (ORR) was the primary end point. Secondary end points were complete response rate (CRR), overall survival (OS), duration of response (DOR) and toxicity. Pooled estimates were derived from fixed or random effect models, depending on the amount of heterogeneity detected. Analysis was carried out separately for high dose (HD) and low dose (LD) IL-2. Sensitivity analyses were carried out. Among 1211 records screened, 13 studies (published 1988 - 2016) were eligible for meta-analysis. Among 410 heavily pretreated patients (some with brain metastasis), 332 received HD-IL-2 and 78 LD-IL-2. The pooled overall ORR estimate was 41% [95% confidence interval (CI) 35% to 48%], and the overall CRR was 12% (95% CI 7% to 16%). For the HD-IL-2 group, the ORR was 43% (95% CI 36% to 50%), while for the LD-IL-2 it was 35% (95% CI 25% to 45%). Corresponding pooled estimates for CRR were 14% (95% CI 7% to 20%) and 7% (95% CI 1% to 12%). The majority of HD-IL-2 complete responders (27/28) remained in remission during the extent of follow-up after CR (median 40 months). Sensitivity analyses yielded similar results. Higher number of infused cells was associated with a favorable response. The ORR for HD-IL-2 compared favorably with the nivolumab/ipilimumab combination following anti-PD-1 failure. TIL-ACT therapy, especially when combined with HD-IL-2, achieves durable clinical benefit and warrants further investigation. We discuss the current position of TIL-ACT in the therapy of advanced melanoma, particularly in the era of immune checkpoint blockade therapy, and review future opportunities for improvement of this approach.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Proteínas Recombinantes / Linfócitos do Interstício Tumoral / Interleucina-2 / Melanoma Tipo de estudo: Prognostic_studies / Systematic_reviews Limite: Humans Idioma: En Revista: Ann Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Grécia

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Proteínas Recombinantes / Linfócitos do Interstício Tumoral / Interleucina-2 / Melanoma Tipo de estudo: Prognostic_studies / Systematic_reviews Limite: Humans Idioma: En Revista: Ann Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Grécia