Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Efficacy of Adoptive Therapy with Tumor-infiltrating Lymphocytes and Recombinant Interleukin-2 in Advanced Cutaneous Melanoma: A Systematic Review and Meta-analysis

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. L-Lysine increased the cytotoxicity effect of doxorubicin in MDA-MB-231 and MDA-MB-468 breast cancer cell lines

    Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskning

  2. TSGA10 and H2AX competition over binding HIF-1 in breast cancer

    Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

  1. Author Correction: Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Author Correction: Tertiary lymphoid structures improve immunotherapy and survival in melanoma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. CTLA-4 blockade boosts the expansion of tumor-reactive CD8+ tumor-infiltrating lymphocytes in ovarian cancer

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Genome-wide CRISPR-Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • U Dafni
  • O Michielin
  • S M Lluesma
  • Z Tsourti
  • V Polydoropoulou
  • D Karlis
  • M J Besser
  • J Haanen
  • Inge Marie Svane
  • P S Ohashi
  • U S Kammula
  • A Orcurto
  • S Zimmermann
  • L Trueb
  • C A Klebanoff
  • M T Lotze
  • L E Kandalaft
  • G Coukos
Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftAnnals of Oncology
Vol/bind30
Udgave nummer12
Sider (fra-til)1902-1913
Antal sider12
ISSN0923-7534
DOI
StatusUdgivet - 1 dec. 2019

ID: 58521355