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Terça-feira, 23.06.15

Newly diagnosed glioblastoma patients treated with an autologous heat shock protein peptide vaccine: PD-L1 expression and response to therapy.

Newly diagnosed glioblastoma patients treated with an autologous heat shock protein peptide vaccine: PD-L1 expression and response to therapy.

 

Category: 
Central Nervous System Tumors
Session Type and Session Title: 
Clinical Science Symposium, Immunotherapy for Central Nervous System Tumors: Biomarkers and Novel Data
Abstract Number: 

2011

Citation: 
J Clin Oncol 33, 2015 (suppl; abstr 2011)
Author(s): 
Orin Bloch, Jeffrey J. Raizer, Michael Lim, Michael Sughrue, Ricardo Komotar, Jonathan Abrahams, Donald O'Rourke, Anthony D'Ambrosio, Jeffrey N. Bruce, Andrew Parsa; Northwestern University, Chicago, IL; Lurie Comp Cancer Ctr of Northwestern Univ, Chicago, IL; The Johns Hopkins Hospital, Baltimore, MD; University of Oklahoma, Oaklahoma City, OK; University of Miami, Miami, FL; Northern Westchester Hospital, Mount Kisco, NY; University of Pennsylvania, Philadelphia, PA; The Valley Hospital, Paramus, NJ; Columbia Univ, New York, NY

Abstract Disclosures

Abstract: 

Background: Standard therapy for glioblastoma (GBM) consists of surgical resection followed by concurrent chemo and radiotherapy with a median overall survival of 16 months. In this phase II, single arm study, addition of an autologous heat shock protein peptide vaccine was evaluated for newly diagnosed GBM. Expression of PD-L1 on peripheral monocytes has been shown to be elevated in GBM patients and was evaluated as a predictor of survival.Methods: Adult patients with GBM underwent surgical resection followed by chemoradiotherapy. Vaccine was generated from tissue obtained at surgery. Key eligibility criteria included ≥ 90% tumor resection and collection of sufficient tumor tissue to generate at least four 25 μg doses of vaccine. Within 5 weeks of completing radiotherapy, patients received weekly vaccinations, followed by adjuvant temozolomide with monthly vaccinations until depletion of vaccine or tumor progression. The primary endpoint was overall survival. Relative PD-L1 expression on circulating monocytes was measured from peripheral blood obtained at surgery. Results: A total of 46 patients from eight centers received the vaccine in addition to standard therapy. Median progression-free survival was 17.8 months (95% Confidence Interval [CI], 11.3-21.6) and median overall survival was 23.8 months (95% CI, 19.8-30.2). The vaccine was well-tolerated with no severe (grade 3 or 4) events attributed to vaccination. The median overall survival for patients with high PD-L1 expression (above the median, 54.5% of monocytes) was 18.0 months (95% CI, 10.0 – 23.3) as compared to 44.7 months (95% CI not calcuable) for low PD-L1 expressors (hazard ratio for death 3.35; 95% CI, 1.36 – 8.23; p = 0.003). A multivariate proportional hazards model revealed MGMT methylation status and PD-L1 expression as the greatest independent predictors of survival. Conclusions: Vaccination with autologous tumor-derived heat shock proteins improves survival compared to standard therapy for newly diagnosed GBM. Systemic immunosuppression driven by peripheral monocyte expression of PD-L1 is a previously unidentified factor that may mitigate vaccine efficacy. Clinical trial information: NCT00905060

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por cyto às 16:57



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