Data from Survivin Dendritic Cell Vaccine Safely Induces Immune Responses and Is Associated with Durable Disease Control after Autologous Transplant in Patients with Myeloma

Abstract

<div>AbstractPurpose:<p>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.</p>Patients and Methods:<p>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<sup>+</sup> and CD8<sup>+</sup> specific T cells were quantified.</p>Results:<p>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).</p>Conclusions:<p>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.</p><p><i><a href="https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-23-2292" target="_blank">See related commentary by Dhodapkar, p. 4524</a></i></p></div>