Another player in the myeloma immunotherapy field, the dendritic vaccine, is starting to show promising results in various clinical trials. 

In a recent study led by Dr. Frederick L. Locke, chair of the Blood and Marrow Transplant Team at Moffit Cancer Center in Florida, a dendritic vaccine targeting a protein call survivin was tested in a phase I clinical trial involving 13 myeloma patients. 

Patients in this study received one dose of the vaccine within 30 days before their autologous stem cell transplant and another dose 21 days after their transplant. 

The patient population for whom this study focused were patients with high-risk disease who still have active myeloma after their induction therapies, before the stem cell transplant.

For context, standard-risk myeloma patients often achieve deep responses to induction therapy and continue with the stem cell transplant to make their responses even deeper and more durable, but high-risk myeloma patients often don't get that benefit. Therefore, the vaccine can give an advantage to these high-risk patients with active disease after induction therapy. 

This is especially exciting, considering those with high-risk disease are often overlooked or underserved when it comes to myeloma clinical trials. 

Dr. Locke shared in a recent press release: 

 “Dendritic cell vaccines have the potential to harness the patients’ own immune system to get them into remission and potentially keep the cancer from coming back.”

If the term "dendritic vaccine" is as new to you as it was to me, here's a little more information on the subject.

Dendritic cells play a crucial role in the immune system, as they ingest foreign proteins, break them down, and then present the resulting fragments (peptides) to activate other immune cells, as Locke elaborated. In the development of the vaccine, the scientists modified the patient's own dendritic cells to express survivin, thus prompting an immune reaction against this protein.

Elevated survivin levels at the time of diagnosis are linked to unfavorable outcomes. Hence, the investigation's hypothesis was that by targeting this particular protein, they could induce an immune response in patients with the most aggressive form of the disease, potentially extending their period of remission.

To boost the presentation of survivin peptides to the immune system, thereby enhancing the chances of evoking a survivin-specific response, Locke and the research team engineered the dendritic cells to express a version of the entire protein.

This version featured a mutation designed to enhance safety without compromising its ability to stimulate the immune system.

The AACR press release shares the results of the study: 

Study results showed that the vaccine in combination with ASCT was well tolerated, with only minor adverse effects observed. Furthermore, the vaccine induced survivin-specific immune responses. Specifically, circulating survivin-specific CD4 T cells and CD8 T cells significantly increased in approximately 35% and 30% of patients, respectively. Antibodies against survivin peptides were detected in 2 out of 13 patients at baseline and 9 out of 13 patients after vaccination and ASCT. “Overall, 85% of patients had either a T-cell response or an antibody response against survivin,” said Locke.

Seven patients experienced an improved clinical response at 90 days post-transplant, all of whom showed survivin-specific immune responses. After a median follow-up of 4.2 years, six out of these seven patients were alive and remained disease-free after treatment. The estimated four-year progression-free survival was 71%. “These results compared very favorably to historical data suggesting the four-year progression-free survival of this patient population to be approximately 50%,” said Locke.

To read the entire press release on this promising study, read here: A Dendritic Cell Vaccine Was Safe and Induced Immune Responses in Patients With Multiple Myeloma