The options for Patients with acute myeloid leukemia (AML) are linked with high comorbidity rates and poor survival. Dendritic Cell Therapy (DCT) is a promising alternative treatment. The Dendritic cell vaccine, DCP-001, was developed from an AML-derived cell line, that combines multi-leukemia antigens and features of allogenic DC vaccine.The result shows that DCP-001 vaccination is feasible and leads to boosting the immune system.
12 patients with acute myeloid leukemia (AML). Patients (age range 58–71) enrolled were either in CR1/CR2 (n = 5) or had smoldering disease (n = 7). Patient must not have uncontrolled active infection, previous immunotherapy in the last 3 months, and previous allogeneic peripheral stem cell transplantation.
DCP-001 was manufactured according to good manufacturing practice (GMP) regulations. The cells were cultured in a cocktail of GM-CSF, TNFα, and IL-4 in the presence of mitoxantrone to accelerate DC differentiation, followed by maturation in the presence of prostaglandin-E2, TNFα, and IL-1β. Quality control (QC) included microbiological controls and QC release tests for cell viability and number, phenotype and potency through T cell priming in a mixed leukocyte reaction (MLR). Clinical lots were gamma irradiated to prevent cell replication and cryopreserved in Cryostor CS10.
Patients received four bi-weekly intradermal (ID) DCP- 001 vaccinations (2–4 four injections of 0.5 mL each) in the upper leg. The first cohort (n = 3; patient 001, 002, 004) received 10 million cells/vaccination, the second cohort (n = 3; patient 005, 006, 007) 25 million cells/ vaccination, and the third cohort (n = 3 patient 008, 011, 012) received 50 million cells/vaccination. The third cohort was extended with three patients (patient 013, 014, 015). Of note, patient 001 received two booster vaccinations of 10 million cells, 13.5 months after the fourth vaccination (t = 0) at 2- week intervals.
Safety and feasibility
DCP-001 vaccination was well tolerated, safe and feasible. Six patients experienced severe adverse events (SAE) during the study (002, 004, 005, 007, 011 and 014). Two patients died before completing the study due to pneumonia (005) and disease progression (014). Neither of these deaths were related to study treatment. Two patients discontinued study treatment); SAEs in patients 004 (myocardial infarct) and 007 (vasovagal collapse) did not lead to discontinuation and both patients in fact proved to be long-term survivors. AEs were of CTC grade 1 or 2 and most were judged as unrelated to study treatment. The most common AEs were injection site reactions(6 patients), anemia (4 patients), thrombocytopenia (3 patients), fatigue (3 patients), pain in extremity (3 patients), and nausea (3 patients).
At the end of the study (day 126), 9 out of 12 (75%) patients were alive. Eight patients completed all assessments and for those four patients who did not complete the study, reasons were disease progression (002), death due to disease progression (014), pneumonitis/pneumonia (005) and candida endocarditis (011).
Six out of 12 patients were in CR at study end and 5/12 experienced persistent disease. All patients, except for one, who were in CR at end of study, were in CR1 or CR2 at baseline. One patient (001) with smoldering disease reached CR at the end of the study. This patient had circulating blast counts of 0.05 × 109/L and bone marrow blasts of 7% at baseline.
At present (December 2017) one patient is still alive. Based on the presence or absence of circulating leukemic blasts patients could be divided into two groups, which corresponded to short-(≤ 6 months, median overall survival 3 months, range 2–6 months) and long-term survivors (> 6 months, median overall survival 36 months, range 7–63 months), respectively. The two groups showed strikingly different patterns in peripheral leukemic blast and T cell counts during treatment. Patients with detectable peripheral blast died within 6 months post-treatment (short- term survivors). Patients without detectable leukemic blasts in peripheral blood (or rapidly dropping below the detection threshold) showed remarkably prolonged survival, with one patient still alive at the time of writing and 64 months after study entry and the other patients surviving for 7, 36, 22, 63, and 36 months.
In conclusion, DCP-001 vaccination in elderly AML patients is safe, feasible and leads to the induction or boosting of multifunctional antitumor immunity. In patients with CR and stable peripheral T cell rate-prolonged overall survival was observed (median 36 months). These promising data warrant further testing of this allogeneic off-the-shelf DC vaccine in AML patients in post-chemotherapy complete remission.