32O - Successful use of interferon-alpha and adoptive T cell therapy for metastatic melanoma patients failing other treatment options

Date 14 December 2018
Event ESMO Immuno-Oncology Congress 2018
Session Proffered Paper session II
Topics Melanoma
Presenter Monique van der Kooij
Citation Annals of Oncology (2018) 29 (suppl_10): x11-x16. 10.1093/annonc/mdy485
Authors M.K. van der Kooij1, E.M.E. Verdegaal1, M. Visser1, L. De Bruin1, C.E. Van der Minne1, S.J. Santegoets1, M.J. Welters1, J.B.A.G. Haanen2, E. Kapiteijn1, S.H. van der Burg1
  • 1Medical Oncology, Leids Universitair Medisch Centrum (LUMC), 2333 ZA - Leiden/NL
  • 2Medical Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL

Abstract

Background

Current standard-of-care immunotherapies target the interaction between tumor and T cells. However, frequently there are insufficient numbers of tumor-specific T cells present. Hence, these patients may benefit from adoptive cell transfer (ACT) with melanoma-specific T cells. The general conditioning and maintenance treatment for ACT consists of lymphodepleting chemotherapy with or without total body irradiation, and post-transfusion high-dose IL-2. In our hospital we replaced this rather toxic treatment scheme with low-dose interferon-alpha (IFNa).

Methods

Twenty-four patients with progressive metastatic melanoma received up to three infusions with ex vivo expanded tumor infiltrating lymphocytes (TIL) every three weeks, ranging between 1-10 x 108 T cells per infusion. One week before the first TIL infusion patients started with daily subcutaneous IFNa injections. These injections were continued for eleven weeks as a maintenance treatment. Total blood count was measured before the start of IFNa, and before each TIL infusion. Furthermore, serum and PBMC were collected at these time-points. Twelve weeks after the first TIL infusion the patients received a radiological response evaluation.

Results

The combination of IFNa and ACT is safe and well tolerated. IFNa causes a mild lymphopenia, neutropenia and leukopenia. Both responders and non-responders show a decrease in these blood counts after one week of IFNa. Strikingly, persistence of leukopenia and in particular neutropenia predicts the response to TIL therapy. Furthermore, high leukocyte/lymphocyte and platelet/lymphocyte ratios are predictive biomarkers for response to treatment. Clinical benefit was seen in 7 out of 24 (29%) patients with stable disease for an average of 36 weeks. Although nineteen patients failed extensive pre-treatment with BRAF/MEK inhibitor and/or anti-PD1 and/or anti-CTLA4, five of them still displayed stabilization of disease (26.3%) after ACT.

Conclusions

The persistence of leukopenia induced by low-dose IFNa is a predictor of response to TIL therapy. Furthermore, this treatment combination is a viable option for heavily pre-treated metastatic melanoma patients.

Editorial acknowledgement

Clinical trial identification

Local Ethics Committee P04.085.

Legal entity responsible for the study

Medical Oncology, Leiden University Medical Center.

Funding

KWF (Dutch Cancer Society).

Disclosure

E.M.E. Verdegaal: In relation to research: Affiliations or financial involvement: ISA pharmaceuticals B.V., AIMM Therapeutics, PamGene. J.B.A.G. Haanen: Advisory boards, consultation and lectures: Pfizer, Bayer, MSD, BMS, Ipsen, Novartis, Roche/Genentech, Neon Therapeutics, Celsius Therapeutics, Gadeta BV, Immunocore. Grants to NKI: BMS, MSD, Novartis, Neon Therapeutics. E. Kapiteijn: Advisory boards: Roche, BMS, MSD, Novarits, Pierre-Fabre, Genzyme-Sanofi, Eisai, Servier, Sirtex, Delcath (for which LUMC received honoraria). Grant support to LUMC: Novartis, BMS. S.H. van der Burg: Advisory boards: ISA Pharmaceuticals B.V., PCI-Biotech, IO-Biotech; Corporate grant support: Innate Pharma, Kite Pharma EU B.V., AIMM Therapeutics; Service agreements: ISA Pharmaceuticals B.B., IO Biotech. All other authors have declared no conflicts of interest.