Robust Sipuleucel-T Immune Activity Is Detailed in Pooled Data Analysis

Ben Leach
Published: Wednesday, Oct 24, 2012
Dr. Petrylak

Daniel P. Petrylak, MD
Professor, Medical Oncology Director, Prostate Cancer Research Group Yale Cancer Center Leader, Genitourinary Cancers Medical Oncology Team Smilow Cancer Hospital at Yale-New Haven
New Haven, CT

Patients who received sipuleucel-T (Provenge) developed immune parameters that correlated with improved overall survival, giving researchers a better understanding of how the immunotherapy works at a cellular level and suggesting that these parameters should be the focus of further studies on the treatment.

The results of the study were published in the journal Cancer Immunology, Immunotherapy.1

The FDA approved sipuleucel-T in 2010 to treat patients with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). The autologous cellular immunotherapy was the first of its kind approved to treat any type of cancer. Since then, the treatment has received a fair degree of scrutiny, especially since the clinical trials that led to its approval demonstrated an improvement in overall survival, but not in progression-free survival.

The study results should help put such concerns to rest, said Daniel P. Petrylak, MD, one of the authors of the paper. “This is evidence,” he said, “that this product works.”

Sipuleucel-T is created by culturing a patient’s own isolated peripheral blood mononuclear cells, including antigenpresenting cells (APCs). When each dose is prepared, those cells are activated with a fusion protein of the antigen prostatic acid phosphatase linked to granulocyte-macrophage colony-stimulating factor. As a result, when the treated cancer cells are reintroduced into a patient’s body, T cells attack them. The treatment is given to patients in three doses.

Table. Patient Characteristics in Three Key Studies1

  Sipuleucel-T Control
Patients 488 249
Median age 72 71
ECOG status n (%)
0 393 (80.5%) 199 (79.9%)
1 95 (19.5%) 50 (20.1%)
Gleason sum n (%)
≤6 74 (15.2%) 31 (12.4%)
≥7 413 (84.6%) 217 (87.1%)
Bone metastases >10 n (%) 211 (43.2%) 97 (39.0%)

ECOG indicates Eastern Cooperative Oncology Group.

In order to determine which immune parameters correlate with better overall survival, the study’s authors analyzed three phase III studies⎯D9901, D9902A, and IMPACT⎯in which a total of 737 participants with mCRPC had been randomized 2:1 to receive either sipuleucel-T or a control product (Table). More detailed data involving peripheral immune responses were available only for a subset of patients who took sipuleucel-T during the IMPACT trial, which investigators called a limitation of this review study.

The three parameters the authors used to characterize immunologic responses were the number of APCs, APC activation (measured by CD54 upregulation), and total nucleated cell (TNC) numbers observed in successive doses of sipuleucel-T prepared for study participants.

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