Background

Immunotherapy of cancer has changed the paradigm of treatment of many tumours, especially non-small cell lung cancer (NSCLC). The use of immune-checkpoint inhibitors (ICI) is associated in some patients with the development of new immune-related adverse effects (ir-AEs). Our aim was to study if there is any correlation between the appearence of ir-AEs and the efficacy of ICI.

Methods

We collected data of 66 patients diagnosed of advanced NSCLC and treated with ICI in monotherapy at our institution between December 2015 and May 2019. Several variables as clinical, tumour-related and therapeutical were included and univariate and multivariate Cox regression analysis were performed.

Results

Cohort of 50 men and 16 women, median age of 67 years and 80% with Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. 66% were active or ex-smokers and 34% had never smoked. 62% of patients had adenocarcinoma histology, 32% scamous and 3% had not otherwise specified (NOS) carcinoma histology. 3% of patients had III-B stage at the moment of start of immunotherapy, 36% M1a, 35% M1b and 24% M1c. 2 patients had driver mutations in EGFR gene. 53% of patients had unknown PDL1 status; 9% had no PDL1 expression, 9% low expression and 27% high expression. 82% of patients had progressed to prior line of treatment, while 18% were treatment-naive. irAEs occured in 55% of patients; 11% developed grade 3 to 4 toxicities. More frequent irAEs were fatigue (61%) and rash (32%). Significant statistical variables in univariate analysis were included in multivariate analysis by Cox regression. The appearence of any grade of toxicity was associated with improved progression-free survival (PFS) (median 5.2 months vs 2.7 months; HR 3.53; p = 0.018; 95% CI [1.24-10.07] ). The use of corticosteroids during treatment with ICI was not related to PFS.

Conclusion

Appearance of immune-related adverse effects during treatment with ICI was associated with better outcomes in our population. The use of corticosteroids during immunotherapy didńt have any deleterious effect on the efficacy of treatment.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

FimaVacc is a vaccine formulated by the photosensitising compound fimaporfin and a toll-like receptor (TLR) agonist, and is administered intradermally followed by illumination of the vaccination site. In preclinical studies, fimaVacc has been shown to improve MHC class I antigen presentation, resulting in strongly enhanced cytotoxic and helper T-cell responses to various types of peptide and protein vaccines.

Methods

A phase I clinical study with fimaVacc has been performed in healthy volunteers to study the safety and immunogenicity of this novel vaccine. The subjects were vaccinated with HPV16 E7 peptides and Keyhole Limpet Hemocyanin (KLH) protein, serving as model antigens for peptide- and protein-based vaccines. Both antigens were formulated with fimaporfin and the TLR3 agonist poly-ICLC (Hiltonol) and administered in up to three vaccinations. Local and systemic adverse effects were assessed for safety, and cellular and humoral immune responses were analysed by ELISPOT, flow cytometry and ELISA assays to determine the immunogenicity of fimaVacc.

Results

The principle of the fimaVacc technology will be presented, together with preclinical results showing that fimaVacc strongly enhances both cellular and humoral immune responses and improves anti-tumour effects in mouse models. The clinical study showed that intradermal vaccination with fimaVacc was well tolerated, with no systemic side effects and generally only mild local reactions. Elispot analysis showed that fimaVacc can significantly increase the number of healthy donors displaying a T-cell response to HPV peptide vaccination. Furthermore, Elispot and flow cytometry analyses demonstrated an enhancement of both HPV-specific CD4+ and CD8+ T cells upon fimaVacc treatment.

Conclusion

The photochemically based fimaVacc vaccination technology can be applied safely in humans, and enhances T-cell responses to an HPV peptide vaccine over what is achieved in a control group which received antigen + adjuvant without fimaVacc.

Clinical trial identification

NCT02947854.

Legal entity responsible for the study

PCI Biotech AS.

Funding

PCI Biotech AS.

Disclosure

S. Janetzki: Advisory / Consultancy: PCI Biotech AS. V.T. Edwards: Full / Part-time employment: PCI Biotech AS. H. Olivecrona: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: PCI Biotech AS. S.H. van der Burg: Advisory / Consultancy: PCI Biotech AS. T. Otterhaug: Shareholder / Stockholder / Stock options, Full / Part-time employment: PCI Biotech AS. A. Hogset: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: PCI Biotech AS. All other authors have declared no conflicts of interest.

Background

In recent years, research has focussed on targeted immunotherapeutic therapies in UM are disappointing and questions remain regarding the mechanisms leading to metastases and the tumor’s resistance to treatment. Genetic predictors for metastatic tumor behavior is the loss of BRCA1-associated protein 1 (BAP1) expression. NF-κB is a principal coordinator of innate immunity and inflammation and has emerged as an essential endogenous tumor promoter. We hypothesize that genetic changes not only influence the immunological microenvironment but also drive metastasis in UM and that NC-NFκB proteins (p52 & RelB) are the consequence of a highly-inflammatory profile.

Methods

In our study, based on the expression of CD3 (infiltrating lymphocytes) and CD68 (infiltrating macrophages), we divided our study cohort into two categories: UM with inflammation and UM without inflammation. Expression of BAP-1 and NC-NFκB proteins (RelB & p52/NFκB2) was evaluated using immunohistochemistry. Real-time PCR was performed on 60 frozen tumor samples. The presence of p52/RelB heterodimer detected by Co-immunoprecipitation in UM with inflammation.

Results

In the inflammation group, activation of NC-NFκB proteins found in 82% and 64% of cases while the loss of BAP-1 was observed in 82% of cases. Loss of BAP-1 protein along with activation of NC-NFκB proteins was seen in 70% of cases of the inflammation group. Loss of BAP-1 along with activation of C-NFκB proteins was statically significant with inflammatory factors such as CD34 + (p = 0.036), IL-6 (p = 0.012), LBD>15mm (p = 0.031) and epithelioid cell type (p = 0.027). In the inflammation group fold-change value of RelB (5.21) & NFκB2 (4.65) genes was reduced to 2.85 (RelB) & 2.34 (NFκB2) gene in the non-inflammation group. Mutation of BAP-1 was more frequently seen in the inflammation group than the non-inflammation group. Loss of BAP-1, along with the activation of NC-NFκB proteins, was associated with reduced metastasis-free survival and overall survival (p < 0.05).

Conclusion

Our preliminary data reveal that in an inflammation group loss of BAP-1 showed the synergistic role with the activation of NC-NFκB proteins and are the poor prognostic indicators of overall survival.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Colorectal Cancer (CRC) is the second leading cause of cancer mortality worldwide. Effective and non-invasive biomarkers are needed to improve early diagnosis and disease management. Immune cells play a key role in tumor progression. Circulating immune cell count is a potential cancer biomarker, as indicated by the association of high blood neutrophil-to-lymphocyte ratio with poor prognosis in patients with cancer. The study goal was to determine the correlation between circulating immune cell counts and immune cell-specific RNA signatures and to evaluate the signature potential for CRC detection.

Methods

The transcriptome profiles of peripheral blood mononuclear cells from 561 Asian and Caucasian subjects (189 CRC, 115 advanced adenomas, 39 other cancers, 218 controls without colorectal lesions (CON)) were generated by RNA-seq on the Illumina platform. Neutrophils, lymphocytes and monocytes counts were obtained by standard hematology testing. Specific RNA signatures for neutrophils, monocyte/macrophages, T cells, CD4, CD8, B cells, NK cells were compiled from literature. The mean expression level of all genes in each Immune cell signature was calculated and used for statistical analyses.

Results

The main immune cell type RNA signatures showed correlation with the relative cell counts (r: 0.4-0.6), indicating the validity of the RNA signatures. Myeloid cell (monocyte/macrophage and neutrophil) RNA signatures were the most significantly upregulated in CRC compared to CON (p < 0.01), whereas the T-cell signature was the most significantly downregulated. Interestingly, the NK cell RNA signature was strongly upregulated in the Asian compared to Caucasian patients, which was mirrored by a higher lymphocyte cell count, in line with a previous study.

Conclusion

This study shows that measuring specific immune cell type by RNA signatures correlate with traditional cell counting methods, enabling the extraction of valuable clinical information from blood transcriptomic data. This data suggests that both blood myeloid and T cells RNA signatures are promising biomarkers for CRC detection. Further biomarker development would require the optimization of the RNA signatures to validate and increase their diagnostic power.

Legal entity responsible for the study

Novigenix.

Funding

Novigenix.

Disclosure

S. Morgenthaler: Advisory / Consultancy: Novigenix. L. Ciarloni: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novigenix. G. Dorta: Advisory / Consultancy: Novigenix. S. Hosseinian Ehrensberger: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novigenix. All other authors have declared no conflicts of interest.

Background

Immune checkpoint inhibitors (ICIs) are a new option for salvage therapy in relapsed/refractory (r/r) Hodgkin lymphoma (HL) and non-Hodgkin lymphoma. Patients with HIV-related lymphoma may benefit not only from the anticancer activity of ICIs, but also from its potential anti-HIV effect. The publications on ICIs in HIV-related lymphomas is limited by a few case reports.

Methods

Nine patients with r/r HIV-related lymphoma were treated with nivolumab (nivo) between 2017-2019. Median follow-up time was 397 days [45-889]. The end points were response to therapy, immune-related adverse effects (IRAE) and overall survival (OS) at 12 months. LYRIC criteria for assessing FDG-PET/CT were applied.

Results

The main characteristics of the study population and outcomes are presented in the table. Median number of prior lines of therapy was 3 (range, 2-4). Four patients received low dose of nivo as monotherapy [NCT03343665] with median of 12 courses 12 (7-12), 5 patients in combination with bendamustine and gemcitabine [NCT03259529] with median of 4 courses 4 (3-11). The median of CD4+ was 382 c/mcl (range, 45-560). The only one patient who did not receive cART due to acute renal failure died early from undetermined cause. Overall response rate (ORR) was 89% with the median time 104 days (73-517); complete remission (CR) was 67% with the median time 107 days (75-265). IRAE were not registered. OS at 12 months was 88.9%.

Table: 61P

Conclusion

Overall response rate to nivo in patients with HIV-related lymphomas was 89%, one-year OS – 88.9%. Immune-related adverse effects were not registered. Preliminary data suggest that nivo seems to be an effective and safety treatment option for r/r HIV-related lymphoma.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.