Although the development of new therapies for multiple myeloma has significantly improved response rates and outcomes for patients with the blood cancer, most patients eventually relapse, including those who initially achieved remission.
A phase I study is investigating whether a dendritic cell vaccine transduced with an adenoviral vector encoded with full-length survivin known as DC:Ad-S, with mutations neutralizing its antiapoptotic function, could safely generate immune response and deepen clinical responses when administered before and after autologous stem cell transplantation in patients with multiple myeloma. Study findings showed the therapy was safe and associated with durable clinical responses. This treatment strategy may have the potential to deepen responses achieved with autologous stem cell transplant as an alternative to consolidation or multiagent maintenance therapy. Ciara L. Freeman, MD, PhD, Assistant Member, Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center, and colleagues published the findings in Clinical Cancer Research.
Ciara L. Freeman, MD, PhD
Study Methodology
This phase I first-in-human clinical trial (ClinicalTrials.gov identifier NCT02851056) evaluated the safety of DC:Ad-S in 13 patients newly diagnosed with multiple myeloma who had not achieved a complete response with induction therapy. The patients received one dose of the vaccine within 30 days before standard-of-care autologous stem cell transplantation and another dose approximately 21 days after transplantation.
To increase the number of survivin peptides presented to the immune system to improve the likelihood of triggering a survivin-specific response, the researchers engineered the dendritic cells to express a version of the entire protein, with a mutation to increase safety without compromising immunogenicity.
Key Results
The investigators found that the vaccine in combination with autologous stem cell transplantation was well tolerated, with minor adverse effects observed. Detectable antisurvivin antibodies increased from baseline in 9 of 13 patients (69%), and 11 of 13 (85%) achieved either a cellular or humoral immune response to DC:Ad-S. Seven patients had an improved clinical response at day 90, all of whom had achieved an immune response, and six of seven patients remained event-free at a median follow-up of 4.2 years. Estimated progression-free survival at 4 years was 71% (95% confidence interval = 41%–88%).
“Two doses of DC:Ad-S, one given immediately before and another after autologous stem cell transplant, 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,” concluded the study authors.
Translational Relevance
Frederick L. Locke, MD
“Our study showed that we can target survivin with a vaccine-based approach and induce immune responses, and it suggested that this strategy could ultimately help improve patient outcomes,” said senior study author Frederick L. Locke, MD, Chair of the Blood and Marrow Transplant and Cellular Immunotherapy Department at Moffitt Cancer Center. “Larger, randomized studies are needed to confirm our findings and to assess whether moving vaccination to earlier in the disease course would be beneficial in preventing patients from developing aggressive forms of myeloma.”
Disclosure: Funding for this study was provided by the National Cancer Institute; Leukemia & Lymphoma Society; and donations from the Hawkins, Hyer, and Thiel families. For full disclosures of the study authors, visit aacrjournals.org/clincancerres.
