Dendritic Vaccine Improves Survival in Recurrent Glioblastoma

Haydia Haniff
Published: Wednesday, Feb 19, 2014
Dr.Andrew T. Parsa

Andrew T. Parsa, MD, PhD

 

Chair, Neurological Surgery
Northwestern Memorial Hospital
Chair, Department of Neurological Surgery
Feinberg School of Medicine
Northwestern University
Chicago, IL

A personalized vaccine being tested as a therapy for recurrent glioblastoma multiforme (GBM) improved patient survival compared with standard treatments, according results of a study published in Neuro-Oncology1 that will help move the agent forward in clinical development.

The therapy tested in the multicenter, singlearm phase II trial was heat-shock protein peptide complex-96 (HSPPC-96), an autologous treatment made from dendritic cells extracted from patient’s tumor tissue after surgical resection with the aim of killing any tumor cells left behind. The vaccine contains a precise antigenic fingerprint of the patient’s cancer, and only targets cells with this fingerprint, greatly reducing the risk of off-target effects.

HSPPC-96 is part of the Prophage Series G-200 vaccine candidates, which have been funded in various studies by the National Cancer Institute and brain research advocacy organizations, according to Agenus Inc, the pharmaceutical developer. The Feinberg School of Medicine at Northwestern University is leading the research effort.

The vaccine’s results compare favorably with historical outcomes of patients with GBM, whose median survival is 15 months from time of diagnosis and 3 to 6 months after recurrence, Bloch et al reported.1 Chemotherapy and radiation following surgery are standard treatments for newly diagnosed GBM, but after recurrence, which is typical in the disease, there are no very effective therapies, said Andrew T. Parsa, MD, PhD, a coauthor of the study and chair of Neurological Surgery at Northwestern Memorial Hospital. The study followed patients who received the vaccine after surgery and standard adjuvant therapy.

Figure. Key Statistics for 41 Patients in HSPPC-96 Vaccine Trial

Key Statistics for 41 Patients
in HSPPC-96 Vaccine Trial
With HSPPC-96, “Survival increased from an average of 33 weeks following progression to about 40 weeks,” said the study’s lead author, Orin Bloch, MD, a neurosurgeon at the hospital, in a press release. He described that result as “a substantial, though not enormous, increase in survival that gives us hope that vaccine therapy, perhaps in combination with other therapies, will increase survival and improve overall care.” In the study, overall survival at 6 months after treatment with HSPPC-96—the primary endpoint—was approximately 90%. After 12 months, nearly 30% of the patients were alive. Additional endpoints included overall survival, progression-free survival (PFS), safety, and immune profiling.

In all, 68 patients with recurrent GBM were screened and underwent surgical resection for the study from October 2007 through October 2011, researchers reported. Nearly 40% of the initial group (27 patients) were excluded postoperatively, including 13 patients from whom the tumor harvested was insufficient to generate the vaccine.

The resulting trial included an intent-to-treat population of 41 patients with a median age of 55 years (21-75 years) who had surgically resectable, recurrent, high-grade GBM. Karnofsky performance scores were >90 for 15 patients (37%), >80 for 20 patients (49%), and >70 for 6 patients (14%). Participants underwent surgery to remove more than 90% of the brain tumor (a gross total resection). The vaccine was then created for each patient using their removed mass, with approximately 7 g of tissue needed to produce a minimum of four 25-mg vaccine doses. The HSPPC-96 vaccine was administered once a week for 4 weeks, then every other week, with a median of 6 doses (range, 1-15 doses). Reasons for discontinuing the vaccine included disease progression (21 patients) and depleted vaccine (13 patients).

After treatment, 90.2% of patients were alive at 6 months (95% CI, 75.9-96.8) and 29.3% were alive at 12 months (95% CI, 16.6-45.7), the authors reported. Median overall survival was 42.6 weeks (95% CI, 34.7-50.5), they wrote. Patients who received a greater number of doses experienced statistically significant better outcomes, with a hazard ratio of 0.85 (95% CI, 0.73-0.99; P = .036) per incremental dosage. There were no treatment-related deaths.

During the trial, there were 37 serious (grade 3–5) adverse events reported. Seventeen could be attributed to the surgical resection, and 1 grade 3 constitutional event was related to the vaccine, the authors reported.


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Provider and Caregiver Connection™: Addressing Patient Concerns While Managing GlioblastomaSep 29, 20182.0
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