Castrate-resistant prostate cancer (CRPC) is a deadly disease which warrants new therapies. Clinical evidence supports a beneficial effect of immune stimulation in CRPC patients shown by sipuleucel-T. Dendritic cells (DC) are the immune system’s professional antigen presenting cells. The use of new DC subpopulations could improve their outcome.
In this phase II trial, HLA-A*02.01 positive chemo-naive CRPC patients were randomly assigned (1:1:1) to myeloid DC (mDC), plasmacytoid DC (pDC) or combined mDC + pDC vaccinations. Patients had disease progression by rising PSA or increase in measurable disease by RECIST 1.1 and PCWG2. Patients received DC vaccination loaded with the tumor-associated antigens MUC1, NY-ESO-1, and MAGE-C2. Radiological responses were assessed on 68Ga-PSMA PET-CT scan (incl. RECIST 1.1), iron oxide-enhanced MRI scan of lymph nodes (nano-MRI) and MRI bones. Primary endpoint is the immunological response post-DC vaccination. Main secondary endpoints are safety and feasibility, radiological PFS and PSA response.
We present the early clinical results of the first 12 patients. Patients were assigned to mDC vaccinations (n=5), pDC vaccinations (n=5) or combined mDC + pDC vaccinations (n=2). All vaccine types were tolerated well (grade 1-2 toxicity in 4/12 patients). Most importantly, 8 of 12 patients (67%) showed radiological stable disease after 6 months using PSMA PET-CT scanning confirmed by (nano-) MRI scans. In patients with at least 9 months follow-up (n=6), 5 still show stable disease. Radiological stable patients showed a trend to an increased PSA doubling time (PSAdt); prevaccination PSAdt was 8.7 months (95% CI: 4,0-13,3) vs. 19.9 months (95% CI: 10,4-29,3) at 6 months.
Clinical responses in the first twelve CRPC patients treated with blood-derived DC vaccinations.
AA: oral anti-androgen therapy (bicalutamide in nine patients and abiraterone plus dexamethason in one patient); DC: dendritic cells; GS: Gleason score; FLS: flu-like symptoms; LHRH: luteinizing hormone-releasing hormone; LN: lymph nodes; mo: months; PD: progressive disease; PSAdt: prostate-specific antigen doubling time; SD: stable disease; SO: subcapsular orchidectomy; UTI: urinary tract infection; vac: vaccinations.
^ vaccination with mDC (patients 1-5), pDC (patients 6-10) or combined mDC + pDC (patient 11 and 12).
# only vaccine-related Common Terminology Criteria for Adverse Events grade 1-2 side effects were seen. The UTI was related to progressive LN metastases.
$ radiological responses were assessed on advanced imaging with 68Ga-PSMA PET CT scans, nano-MRIs and MRI bones using RECIST 1.1 and PCWG2 criteria.* radiological and biochemical progression of disease was already present after 4 months, whereupon DC vaccinations were stopped.
Innovative DC vaccination is feasible and safe in early CRPC patients. Clinical results of the first 12 vaccinated patients showed radiological stable disease in 67% of patients at 6 months.
Clinical trial identification
ClinicalTrials.gov Identifier: NCT02692976. First received: September 30, 2015