Survivin Dendritic Cell Vaccine Safely Induces Immune Responses and Is Associated with Durable Disease Control after Autologous Transplant in Patients with Myeloma
Ciara L. Freeman, Reginald Atkins, Indumathy Varadarajan, Meghan Menges, Jeffrey Edelman, Rachid Baz, Jason Brayer, Omar Castañeda Puglianini, José L. Ochoa-Bayona, Taiga Nishihori, Kenneth H. Shain, Bijal Shah, Dung‐Tsa Chen, Linda Kelley, Domenico Coppola, Melissa Alsina, Scott J. Antonia, Claudio Anasetti, Frederick L. Locke
Abstract
PURPOSE: We investigated whether a dendritic cell (DC) vaccine transduced with an adenoviral vector encoded with full-length survivin (Ad-S), with mutations neutralizing its antiapoptotic function, could safely generate an immune response and deepen clinical responses when administered before and after autologous stem cell transplant (ASCT) for multiple myeloma. PATIENTS AND METHODS: This phase I first-in-human trial (NCT02851056) evaluated the safety of DC:Ad-S in newly diagnosed multiple myeloma not having achieved complete response with induction, given 7 to 30 days prior to stem cell collection and 20 to 34 days after ASCT. Anti-survivin antibodies and CD4+ and CD8+ specific T cells were quantified. RESULTS: A total of 14 patients were treated and 13 included in the primary efficacy analysis. No serious adverse events were attributed to DC:Ad-S vaccine. Detectable anti-survivin antibodies increased from baseline in 9 of 13 (69%) patients, and 11 of 13 (85%) mounted either a cellular or humoral immune response to survivin. Seven patients had an improved clinical response at day +90, all of whom had mounted an immune response, and 6 of 7 patients remain event-free at a median follow-up of 4.2 years. Estimated progression-free survival at 4 years is 71% (95% confidence interval, 41-88). CONCLUSIONS: Two doses of DC:Ad-S, one given immediately before and another after ASCT, were feasible and safe. A high frequency of vaccine-specific immune responses was seen in combination with durable clinical outcomes, supporting ongoing investigation into the potential of this approach. See related commentary by Dhodapkar, p. 4524.