1065P - Advanced pancreatic cancer: adjuvant anti-tolerogenic immunomodulation improves chemoimmunotherapy

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Cancer Immunology and Immunotherapy
Pancreatic Cancer
Translational Research
Presenter Eduardo Lasalvia-Prisco
Citation Annals of Oncology (2014) 25 (suppl_4): iv361-iv372. 10.1093/annonc/mdu342
Authors E.M. Lasalvia-Prisco1, P. Goldschmidt2, F. Galmarini3, J. Vazquez1, E.E. Lasalvia-Galante1, T. Carlevaro1, J.C. Dau4
  • 1R&d, Interdoctors-Telemedical Organization, 11200 - Montevideo/UY
  • 2R&d, Interdoctors-France, Paris/FR
  • 3R&d, Interdoctors-Argentina, 1043 CF - Buenos Aires/AR
  • 4Clinical Services, Translational Medical Center, 11200 - Montevideo/UY

Abstract

Aim

In advanced pancreatic cancer (APC), tumor antigens evidenced in circulating blood were used as immunogens by transference to the lymph system through vaccination sites in skin. The reported antitumor activity of such Autologous Hemoderivative Cancer Vaccine (AHCV) improved when chemotherapy (CH) was associated to enhance antigen cross-presentation. Development of AHCV + CH requires switching of malignancy-induced immunologic tolerance. Translational research identified an immunomodulatory drug set (IDS) that induces such switching by targeting (tg) an immune-committed cell population with each drug of this set: Cimetidine (Cm) tg Dendritic cells; Cyclophosphamide (Cp) tg T-Regulatory (T-Reg) cells; Celecoxib (Cx) tg Myeloid Derived Suppressor cells (MDSC); Metformin (Mf) tg Memory Cells (MC). The aim of this study is to explore APC survival adding the IDS-induced switching to AHCV + CH.

Methods

24 patients (Pts). Inclusion/exclusion criteria: APC, exocrine adenocarcinoma, M1, PS ≤ 2, no M1 Brain, no surgery, chemo or radiotherapy, no comorbility, 4-month treated, 2-arm randomized Arm 1 / Arm 2 (12 Pts each), 1-yr follow-up. Treatment: Arm 1, four 28-day cycles, AHCV (as previously published) day (d) 28 + Gemcitabine 1000 mg/d 1, 8, 15; Arm 2, like Arm 1 + IDS (Cp 50 mg/d) (Cm 400 mg, Cx 400 mg, Mf 500 mg)/12 h, d 1 to 112. Assessment: PBMC, immunochemistry flow cytometry, IDS-targeted cell population count. Survival (% 1-yr and median). Toxicity (Tx) by NCI Common Tx Criteria v 2.0. Statistics: Arm 2 vs Arm 1, Mean comparisons by Student-T test, and survival by Kaplan-Meier/log rank test. Significance: p < 0.05.

Results

Conclusions

In advanced pancreatic cancer, antitolerogenic conditioning of immunity by IDS improves survival obtained with AHCV + CH, safely. Future development is warranted.

Arm 1 (Mean ± SE) Arm 2 (Mean ± SE)
Day 1 Day 112 Day 1 Day 112
DC x ml Lymphoid DR+ lin-CD11- 8200 ± 2710 9100 ± 2800 8018 ± 2562 *12670 ± 2080
Myeloid DR+ lin-CD11 + 5430 ± 1810 5480 ± 1945 5588 ± 1954 *6810 ± 1670
T-Reg %CD4 + CD4 + CD25 hiFoxP3 + 8.1 ± 2.6 7.2 ± 2.1 7.9 ± 2.2 *4.3 ± 1.9
CD4 + CD25 + 20.4 ± 3.3 18.6 ± 3.4 19.8 ± 2.9 *12.6 ± 2.0
MDSC % PBMC Granulocytic Lin-HLA-DR-D33 + CD11b + CD15 + 8.8 ± 3.4 7.1 ± 3.5 9.1 ± 3.5 *5.4 ± 2.7
Monocytic Lin-HLA-DR-D33 + CD11b + CD14 + 0.9 ± 0.1 0.7 ± 0.2 0.8 ± 0.2 *0.4 ± 0.1
MC % CD8 + /CD4 + Effectors CD8 + CD45RO + 42.3 ± 7.1 50.0 ± 6.1 41.6 ± 5.7 *51.6 ± 4.8
Helper CD4 + CD45RO + 55.5 ± 5.0 57.2 ± 5.9 56.1 ± 4.8 *66.9 ± 3.6
TOXICITY (Event Grade 3/4) 2 1
SURVIVAL
Arm 1 Arm 2
Months (Median ± 95%CI) 5.6 (95% CI, 5.0-6.2) *7.1 (95% CI, 6.2-8.1)
1-Yr (%) 16.7 *41.7
* Arm 2 vs Arm 1: p < 0.05

Disclosure

All authors have declared no conflicts of interest.