36P - Immunomodulatory effects of lenalidomide in combination with gemcitabine as first-line treatment in patients with advanced pancreatic cancer

Date 20 November 2015
Event ESMO Symposium on Immuno-Oncology 2015
Session Welcome reception and general Poster viewing
Topics Cancer Immunology and Immunotherapy
Pancreatic Cancer
Presenter Maria Liljefors
Citation Annals of Oncology (2015) 26 (suppl_8): 5-14. 10.1093/annonc/mdv514
Authors M. Liljefors1, F.S. Mozaffari1, H. Mellstedt2, G. Ullenhag3
  • 1Department Of Oncology, Karolinska University Hospital-Radiumhemmet, S 171 76 Stockholm - Stockholm/SE
  • 2Department Of Oncology, Karolinska University Hospital-Radiumhemmet, Stockholm/SE
  • 3Department Of Radiology, Oncology And Radiation Science, University Hospital Uppsala Akademiska Sjukhuset, Uppsala/SE

Abstract

Aim

In a phase I/II study to assess the immunomodulatory and clinical effects of lenalidomide (lena) with standard treatment of gemcitabine (gem) in patients with advanced pancreatic cancer.

Methods

Eligible patients (pts) had locally advanced or metastatic adenocarcinoma of the pancreas and no prior chemotherapy. Lena was given orally once daily for 21 days of a 28 days cycle. Gem was administered weekly as an intravenous (i.v) infusion (1000 mg/m2) for 3 weeks followed by 1 week rest. MDT of lena was established to 25 mg/day in a phase I (PhI) part (Ullenhag GJ et al, 2015)(n = 12) and used in phase II (PhII)(n = 21). In PhII, every other consecutive pts were treated with either lena (Arm A, n = 11) or gem (Arm B, n = 10) during cycle 1 and from cycle 2, all pts received the combination. In PhII, fresh blood samples were taken three times (baseline, after cycles 1 and 2) for phenotyping of T (CD4, CD8), B, NK/NKT cells (CD16/CD56) and regulatory T cells (Treg) by FACS.

Results

Median OS time for all 33 pts was 27 weeks (wks) (range 4-204 wks). For 29 of the 33 evaluable pts, median PFS was 15 wks (range 7-66 wks). The survival rate at 52 wks was 36%. There was no difference in OS, PFS or survival rate at one year comparing pts within the cohorts or between pts in PhI and PhII. In Arm A, a significant increase in absolute numbers of activated (HLA-DR+) CD4 and CD8 T cells, CD8+ effector memory T cells (p < 0.01) and a tendency to increase in absolute numbers of NK/NK-T cells was observed after cycle 1 compared to baseline. After adding gem, most lymphoid subsets were reduced (p < 0.05). A statistical increment in absolute numbers of Tregs was seen after cycle 1 compared to baseline (p < 0.05) which decreased to baseline level after cycle 2. In Arm B, the proportion of lymphoid subsets remained unchanged after cycle 1 and 2 as compared to baseline.

Conclusions

The induced T cell responses were as expected except from a significant increase in Treg after treatment with lena only. The median OS for all pts was comparable to treatment with gem standard therapy. The main finding was that immune responses were as expected but the addition of lena to gem had no impact on survival in patients with pancreatic carcinoma.

Clinical trial identification

ClinicalTrials.gov NCT01547260

EudraCT number 2009-011793-14

Disclosure

M. Liljefors: Attended one compensated advisory board with Celgene Corporation Dec 2011 (regarding another product than lenalidomide). All other authors have declared no conflicts of interest.