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Roberto Ferrara

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    Lunch & Poster Display session (ID 58)

    • Event: ELCC 2019
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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      23P - Immunosenescence (iSenescence) correlates with progression (PD) to PD-(L)1 inhibitors (IO) and not to platinum-chemotherapy (PCT) in advanced non-small cell lung cancer (aNSCLC) patients (pts) (ID 599)

      12:30 - 13:00  |  Presenting Author(s): Roberto Ferrara

      • Abstract


      iSenescence is a remodeling of immune functions with a multifactorial etiology (i.e. aging, chronic inflammation, cancer). Although the absence of CD28 and the expression of CD57 and KLRG1 on circulating T-lymphocytes are hallmarks of iSenescence, the characterization of such phenotype in aNSCLC pts and the correlation with clinical characteristics and benefit from IO or PCT are currently unknown.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      A senescent immune phenotype (SIP) defined as % of circulating CD8+CD28-CD57+KLRG1+ T-lymphocytes was assessed by flow cytometry (FC) on fresh blood from aNSCLC pts treated with IO or PCT in a single institution. A log-rank maximization method was used to identify a SIP cut-off level and dichotomize pts accordingly. The objective was to correlate SIP with clinical characteristics and RECIST response by univariate logistic regression analysis.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      37 aNSCLC pts were evaluable for SIP before IO: 32% ≥ 65 years, 91% non-squamous, 43% KRAS mutated, 51% with PD-L1 expression ≥1%, 8% chemotherapy naïve. 43% had PD, 41% stability (SD), 16% partial response (PR). Median PFS and OS were 2.7 (95% CI 1.8; 7.3) and 13 (95% CI 4.8-NR) months, respectively, median follow-up was 9.3 (95% CI 6.2-14.9) months. SIP (% CD28-CD57+KLRG1+) median value on circulating CD8+ lymphocytes was 12.2% (min 1.7%, max 56.1%). 32% of pts had >20.47% CD8+ lymphocytes with a CD28-CD57+KLRG1+ phenotype, being classified SIP+. SIP status did not significantly correlate with age, pts’ characteristics or CT exposure. 2 (17%) of 12 SIP+ had PR/SD (DCR), vs 19 (76%) of 25 SIP- pts (p = 0.001); median PFS was significantly lower in SIP+ (1.5 months 95% CI 1;2.2) vs SIP- pts (7.4 months 95% CI 5.5, 9.3) (p = 0.001). Among 61 aNSCLC pts treated with 1st line PCT, 18% had PD, 43% SD, 39% PR. SIP median value on circulating CD8+ lymphocytes was 17.9% (min 0.89%, max 66.1%), 43% of pts were SIP+. SIP did not significantly correlate with DCR (OR: 0.82, 95% CI 0.22-3.13, p = 0.82) upon PCT.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      iSenescence, monitored by FC measurement of 3 surface molecules on circulating CD8 + lymphocytes, is observed in 32% and 43% of aNSCLC pts before IO or PCT, respectively. SIP correlated with lower DCR upon IO and not PCT.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      Institut Gustave Roussy.

      213f68309caaa4ccc14d5f99789640ad Funding

      Has not received any funding.

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.