HLA-A2 status correlates with immune response- a positive that this current p3 trial may be successful. There is something about the HLA-A2 that makes these patients more responsive to immunotherapy. These findings don't guarantee that the IMUC p3 trial will succeed but IMO there is a good chance it will.
1223P HLA-A2 and immune checkpoints inhibitors in advanced
non-small cell lung cancer (NSCLC) patients
L. Mezquita1, M. Charrier2, J. Lahmar1, J. Remon1, M.V. Bluthgen1, F. Facchinetti1,
D. Planchard1, A. Gazzah3, L. Dupraz2, J. Adam4, N. Chaput2, B. Besse1
1
Medical Oncology Department, Gustave Roussy, Villejuif, France, 2
Laboratory of
Immunomonitoring in Oncology, UMS 3655 CNRS/US 23 INSERM, Gustave
Roussy, Villejuif, France, 3
Drug Development Department (DITEP), Gustave
Roussy, Villejuif, France, 4
Pathology Department, Gustave Roussy, Villejuif, France
Background: The class I human leucocyte antigen (HLA) molecules play a critical role
in tumor recognition by T cells and the loss of expression seems to be an escape
mechanism of antitumoral immunity. Novel immune-targeting cancer vaccines are
currently developped in HLA-A2 positive patients for modulating the T cells immune
response. We hypothesized that HLA-A2 status could influence the prognosis and
response to immunotherapy.
Methods: Advanced NSCLC patients treated with nivolumab, pembrolizumab or
atezolizumab were prospectively included from Nov. 2013 to Apr. 2016 in our institute.
HLA-A2 status was analysed by flow cytometry; PDL1 was analysed by
immunohistochemistry. Clinical and biological data were collected at baseline and after
cycle 1. Statistical analysis was performed with SPSS v.20.
Results: Out of 125 patients treated, HLA-A2 status was available for 30 patients. 50%
were male, median age was 61 years (29-77); 86% were smokers and 83% had
performance status 0-1. 18 (60%) were adenocarcinoma, 7 (23.3%) squamous and 5
(16.7%) others histologies. 2 NSCLC were EGFRmut, 2 ALK positive, 7 KRASmut, 19
wildtype. PDL1 expression was positive in 8 patients (26.7%), negative in 2 (6.7%) and
unknown in 20 (66.7%). The median of previous lines of treatment was 1 (1-8). The
patient and tumor characteristics were well balanced according to HLA-A2. The
median progression free survival to immunotherapy (iPFS) was 1.47 months
[confidence interval (CI) 95% 1.18-1.7]. HLA-A2 positive status was correlated with
longer iPFS [2.04 vs. 1.3 months, log-rank; p = 0.020]. The median overall survival
(OS) was 38.05 months [CI 95% 8.94-67.16]. The median OS was 55.9 months [CI 95%
9.4-102.15] vs. 22.5 months [CI 95% 0- 54.8] in HLA-A2 positive vs. negative patients
(p = 0.340). In univariate analysis, there was no correlation between outcome and
patient or tumor characteristics.
Conclusions: Our preliminary results suggest that HLA-A2 status could influence the
outcome in NSCLC patients treated with immune checkpoint inhibitors. An updated
analysis on 59 patients will be presented.
