Background: Pancreatic cancer is one of the world’s deadliest malignancies with an average 5-year survival rate of only 9%. Fortunately, immunotherapy is providing encouraging results for treatment of this historically resistant malignancy. Kiromic Biopharma is performing a phase I/II dendritic cell vaccine trial for progressive solid malignancies. We present here a notable response to metastatic pancreatic cancer.
Methods: The patient is a 73-year-old male with the history of a locally advanced pancreatic cancer treated initially with gemcitabine, concurrent 5FU and radiation therapy, and consolidation 5FU, followed by surgical resection in 2009 . Although the patient did well exceeding typical survival curves, the patient’s cancer became metastatic, requiring multiple lines of chemotherapy including FOLFIRINOX, gemzar and abraxane, and most recently Onivyde and leucovorin/5FU in February – August, 2017 for progressive liver and lung metastases. The patient was then enrolled onto Kiromic Biopharma’s DC vaccination trial in March, 2018.
Results: He subsequently received 6 ID autologous dendritic cell vaccinations over 12 weeks, demonstrating a tumor antigen specific immunogenic response by IFN-gamma immunoassay. Total tumor burden (TTB) prior to clinical trial enrollment at the sites of metastatic disease was 2,221mm2, and after completion of the DC vaccination protocol in May, 2018, the TTB increased to 4,466mm2 in June, 2018 (not considered to be pseudo-progression due to a corresponding increase in tumor biomarkers). The patient then received a repeat course of Onivyde and leucovorin/5FU on 8-3-18, completing that course of therapy on 9-14-18, with subsequent TTB decreasing to 2,986 mm2.
Conclusions: The sequential combination of dendritic cell vaccine and chemotherapy resulted in a substantial response with a recession in metastatic tumor burden. A CT scan was obtained just 6 days after the 5 week course of Onivyde was completed, and given the optimal immunotherapy window after the DC vaccination, and the repeat of the same chemotherapy regimen, it is unlikely that chemotherapy alone led to such a rapid decrease in the TTB. Metastatic sites were likely populated by chemo resistant clones that survived the August 2017 administration of the Onivyde regimen. Thus, chemo alone would be unlikely to act so quickly. We hypothesize that there was synergistic activity between the DC immunotherapy and the Onivyde/5FU regimen, accounting for the decrease in TTB between May and September, 2018. Clinical trial information: NCT02705703