Author of

• 11745

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  P2.11 - Poster Session 2 - NSCLC Novel Therapies (ID 209)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11784

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    P2.11-039 - Results from phase III trial of dendritic cell based vaccine immunotherapy in patients with -IIIA stage non-small-cell lung cancer (ID 2767)

    09:30 - 09:30  |  Author(s): A. Ganul
    • Abstract

    Background
    Background. Antitumor immunotherapy to target tumor antigens is considered reasonable and promising in lung cancer (LC). In our early phase of clinical investigation, the safety and efficacy of dendritic cell (DC) based vaccine therapy in patients with non-small-cell lung cancer (NSCLC) have been shown. Following successful early phase results, we designed a phase III trial of DC- vaccine in IIB-IIIA stage NSCLC patients to investigate clinical benefits as the primary endpoint, and immune response markers as secondary endpoint.

    Methods
    One hundred and twenty eligible patients with IIB-IIIA stage NSCLC, ECOG 0-1, without autoimmune disorders were enrolled into the study. Patients were randomly allocated into two groups: 1 st - patients who received DC-vaccine as immunotherapy after surgery (lobectomy or pneumonectomy), 2nd - comparison group of patients who received surgery only. Original construction of DC-vaccine have been used: autologous DCs of monocytic origin loaded with mechanically heterogenized microparticles of tumor cells. Maturation state and functional activity of DCs were evaluated by the expression of cell surface markers CD83/86, HLA-DR and IL-12 p35/p40 mRNA levels. DC in amount 4,62±0,37x106 per injection were injected intravenously in 1-3 courses with 6 months interval. One course consisted of 5 injections with one-month interval. Clinical and immunological monitoring of DC-vaccine immunotherapy was performed.

    Results
    The table summarizes median overall survival (OS) and disease free survival rates at 1, 2, 3, 4 and 5 years for NSCLC patients. Figure 1 Hazard ratio (HR) for recurrence: 0.384; 95:CI = 0.1736 - 0.8510; p = 0.018. The most pronounced changes in the immune system have been defined only after fourth DC-vaccine administration. These changes consist in the significant reduction of T-reg number and their ability to secrete TGF-β, significant increasing the CD8[+]IFN[+] CTL number and functionality and CD4[+] memory cell number, Th1–polarization of immune responses, significant increasing of the RANTES/MIP-1α mRNA ratio (p<0,001). ROC analysis revealed that CD8[+]IFN[+] number (Se=66,67%;Sp=100%; AUC=0,83; p=0,0066), CD4[+] memory cell number (Se=100%;Sp=75%; AUC=0,875; p=0,0094), TGF-β mRNA level (Se=75%;Sp=100%; AUC=0,889; p=0,017), RANTES/MIP-1a mRNA ratio (Se=100%;Sp=83,33%; AUC=0,83; p=0,0066) are the most important immune response markers which associated with clinical outcome after DC-vaccine therapy in NSCLC patients.

    Conclusion
    Adjuvant therapy with DC-vaccine in IIB-IIIA stage NSCLC patients is highly effective approach for prevention metastasis development and recurrence of disease in post-operative period. Patients with low volume disease constitute a target group for the development of effective immune and clinical responses after DC-vaccine therapy.