Vaccine may help boost response to stem cell transplant: Phase 1 trial
Improved clinical response seen in trial involving 13 high-risk myeloma patients
A cell-based vaccine designed to promote immune responses against survivin, a protein that helps tumor cells survive and expand, was found to be safe and feasible for multiple myeloma patients when given around the time of an autologous stem cell transplant (ASCT).
These are the findings of a Phase 1 clinical trial (NCT02851056) involving 13 newly diagnosed myeloma patients considered to be at high risk of a poor prognosis. Notably, seven of these patients saw an improved clinical response three months after transplant and six were alive and free of cancer after about four years.
“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,” Frederick L. Locke, MD, the trial’s principal investigator at the Moffitt Cancer Center in Florida, where the trial was conducted, said in a press release from the American Association of Cancer Research (ACCR).
“Larger, [appropriately-controlled] 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,” added Locke, who is chair of Moffitt’s blood and marrow transplant and cellular immunotherapy department and the study’s senior author, and has a vaccine patent.
The study, “Survivin Dendritic Cell Vaccine Safely Induces Immune Responses and Is Associated with Durable Disease Control after Autologous Transplant in Patients with Myeloma,” was published in Clinical Cancer Research, a journal of the ACCR.
ASCT leads to complete response for about 50%-60% of patients
ASCT is a standard myeloma treatment. Briefly, a person’s own healthy blood stem cells, which can give rise to all other kinds of blood cells, are harvested, then transplanted back into the patient after a course of chemotherapy (called an induction regimen) to kill off as many cancer cells as possible.
This way, the stem cells can repopulate the blood with healthy, non-cancerous cells.
However, even with aggressive induction therapy regimens, ASCT leads to a complete response or better — remission — for about 50%-60% of patients, according to the researchers.
Locke and colleagues had previously shown that a pneumococcal vaccination, a standard vaccine that protects against illnesses caused by a common bacteria, before and after ASCT boosted immune responses in myeloma patients that could also be beneficial for fighting off cancer.
Now, the scientists set out to develop a tumor-targeted vaccine that could maximize treatment responses to ASCT. Their selected target was survivin, a protein that, as the name suggests, suppresses cell death.
While survivin is undetectable in most adult tissues, it is overly produced in almost all cancers, including myeloma, where its presence is associated with a poor prognosis.
To make the vaccine, the team engineered patients’ own dendritic cells to produce a modified version of survivin.
Dendritic cells work by presenting protein fragments, such as those of viruses, to immune T-cells, which then launch an immune attack against these fragments. By producing survivin, the engineered dendritic cells can trigger an immune response against it and the cells producing it.
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.
Targeting survivin may induce immune response against aggressive cancer
“We hypothesized that by targeting this protein, we could induce an immune response in patients who have the most aggressive disease and potentially keep them in remission for a longer period of time,” Locke said.
The researchers then tested the vaccine in 13 adults with high-risk multiple myeloma within a Moffitt Cancer Center-sponsored Phase 1 trial.
Participants had active myeloma and did not achieve a complete response after induction chemotherapy prior to ASCT. This is a known risk factor for a poor prognosis, but these patients are not often included in clinical trials, according to Locke.
“We focused on this patient population because they are most in need of the vaccine,” Locke said.
Patients received a single dose of the vaccine within a month of receiving ASCT and another dose about three weeks after the transplant.
Results showed that the vaccine in combination with ASCT was well tolerated, with side effects attributed to the vaccine that included local site reactions, skin rash, itching, and fever. No serious side effects were associated with the vaccine.
The vaccine was found to significantly increase some type of survivin-targeted immune response in 11 patients (85%). This included increasing the proportion of certain immune T-cell populations programmed to specifically target survivin in about one-third of patients.
Moreover, antibodies against survivin were detected in nine patients (69%) after vaccination plus ASCT, while these were present only in two patients (13.4%) at the study’s start.
7 patients (54%) saw improved clinical response at 3 months post-transplant
Three months post-transplant, seven patients (54%) saw an improved clinical response. These included four patients who showed a complete response, and three others who converted from a partial response after the induction regimen to a very good partial response.
All of these patients showed an increase in immune responses against survivin.
After a median 4.2 years of follow-up, six of these seven patients were alive and cancer-free. Across the entire group of trial participants, estimated 4-year overall survival was 85% and progression-free survival after four years 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%,” Locke said.
Overall, “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,” Locke added.
The researchers called for more research into the vaccine.
“Methods to enhance the immune potentiating capacity of the vaccine to increase the fold expansion of survivin-specific T cells may be warranted, as is the exploration of utilizing the vaccine as an earlier line of therapy or in alternate disease states,” they wrote.
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