Combined chemoimmunotherapy of castrate-resistant prostate cancer with dendritic-cell based vaccine DCVAC/Pca.

Konference: 2014 50th ASCO Annual Meeting - účast ČR

Kategorie: Nádorová biologie/imunologie/genetika a buněčná terapie

Téma: Postery

Číslo abstraktu: 3095

Autoři: MUDr. Michal Podrazil; RNDr. Daniela Rožková, Ph.D.; PharmDr Jitka Fučíková, Ph.D.; doc. PaedDr. RNDr. Stanislav Katina, Ph.D.; Prof. MUDr. Radek Špíšek, Ph.D.; Prof. MUDr. Jiřina Bartůňková, DrSc.


Background: Appropriate combination of tumor mass reduction and neutralization of tumor-induced immunosuppression might potentiate the induction of anti-tumor immunity. We performed an open label, single arm Phase I/II clinical trial in patients with metastatic castrate resistant prostate cancer (mCRPC) eligible for docetaxel using autologous mature dendritic cells pulsed with killed LNCap prostate cancer cell line, DCVAC/PCa. 

Methods: Eligible patients had progressive mCRPC despite androgen deprivation. None of the patients received abiraterone or enzalutamide. DCVAC/PCa treatment consisted of, on average ten doses of 1x107 dendritic cells injected s.c. Treatment comprised of initial 7d administration of metronomic cyclophosphamide, and subsequent 2 doses of DCVAC/PCa. Patients then started docetaxel (75 mg/m2) and prednisone (5 mg twice daily) treatment administered every 3-weeks and DCVAC/PCa was given every 6 weeks up to a maximum number of doses manufactured from one leukapheresis. The primary end point was safety, the secondary end-point immune response. Overall survival (OS) was compared to the predicted OS according to Halabi and MSKCC nomograms. 

Results: Data from twenty-five patients were evaluated. The mean age at the start of immunotherapy was 67 years, median PSA 109 ng/ml and Hb 11,9 g/dl. 48% patients had GS ≥8. No serious DCVAC/PCa-related adverse events have been reported. There were no clinical or laboratory signs of autoimmunity. Median OS was 19 months (95% CI: 14.69-23.31) while the predicted median OS was 12 months (95% CI: 11.19-12.81). We observed no significant changes of the peripheral blood Tregs and MDSCs during the course of the trial. Long-term administration of DCVAC/PCa led to the induction and maintenance of the stable levels of T cells specific against multiple tumor antigens including PSA, NY-ESO1, MAGE-A1 and MAGE-A3. 

Conclusions: In patients with mCRPC, the alternate administration of DCVAC/PCa cancer immunotherapy and docetaxel results in the stabilization of the disease progression and longer than expected survival. Chemotherapy does not preclude the induction of tumor specific T cells. Clinical trial information: 2009-017259-24.

J Clin Oncol 32:5s, 2014 (suppl; abstr 3095

Datum přednesení příspěvku: 1. 6. 2014