Dendritic Cell Vaccine Shows Promising Results in Multiple Myeloma Patients
Dendritic cell vaccines have found success in treating several kinds of cancer, including breast cancer and lung cancer, and now, a new dendritic cell vaccine has shown promising results in treating high-risk multiple myeloma patients.
A new study authored by Frederick L. Locke, MD, chair of the Blood and Bone Marrow Transplant and Cellular Immunotherapy Department at Moffitt Cancer Center, highlights the safety and success of administering a dendritic cell vaccine before and after autologous stem cell transplant (ASCT) in inducing immune response in patients with multiple myeloma.
Multiple Myeloma Treatment
Multiple myeloma is a rare, chronic and incurable cancer that makes up just 1% of all hematologic malignancies worldwide. The current standard of care involves using high-dose chemotherapy induction therapy before ASCT. But, when the myeloma is still active even after induction therapy, it can negatively impact prognosis.
Other treatment options for multiple myeloma include:
- CAR T therapies - Moffitt offers options for relapsed or refractory multiple myeloma that target B-cell maturation antigen (BCMA) to help immune cells seek and destroy cancerous cells. Additionally, citacabtagene autoleucel, a chimeric antigen receptor T cell therapy, may increase response rate and reduce the risk of disease progression.
- EMMA - The Ex Vivo Mathematical Myeloma Advisor (EMMA), found only at Moffitt, is a personalized medicine tool that provides recommendations for multiple myeloma care by testing a person’s sensitivity to drugs concurrently – individually and in combination. EMMA uses a powerful digital microscope to document cell reactions, eliminating a trial-and-error approach.
- Multiple myeloma precursor clinic- This specialty Moffitt clinic treats those with Monoclonal Gammopathy of Undetermined Significance (MGUS), which can lead to multiple myeloma. The clinic’s goal is to delay or preven multiple myeloma complications, including kidney failure and the potential need for dialysis.
Dendritic Cell Therapy
Dendritic cells make molecules that activate the immune system and can help induce antitumor immunity. Dendritic cell vaccine therapy is a newer treatment option that combines cell therapy and a vaccine. By harvesting and preparing dendritic cells with specific peptides or tumor antigens, they can be re-injected back into the patient’s body to trigger an immune system response.
The goal of such therapy is to harness the immune system’s natural capabilities to fight cancer growth and help patients reach remission – and stay there longer – with potential to prevent the cancer from returning.
Other dendritic cell discoveries at Moffitt include:
- Immunotherapy drugs targeting the TIM-3 protein found on dendritic cells to activate T cells
- Dendritic cell vaccine for leptomeningeal disease (LMD) from Triple-Negative Breast Cancer (TNBC) or HER2+ Breast Cancer (HER2+BC) administered intrathecally
- A clinical trial to stimulate the body’s immune system response to leptomeningeal disease
- Direct tumor injection to stimulate dendritic cells through the CD40 and interferon β (IFNβ) pathways for non-small cell lung cancer, working in conjunction with immune checkpoint inhibitors to produce even stronger responses
The Study
Dr. Locke’s study focused on patients with remaining active myeloma even after induction, as this population is most in need of the vaccine.
Researchers created this particular dendritic cell vaccine by engineering patients’ own dendritic cells to express survivin, an inhibitor of apoptosis protein (IAP) that is overexpressed in a wide spectrum of tumors, preventing cancer cell death and promoting malignant cell growth and treatment resistance. By presenting the immune system with survivin peptides, the goal was to induce a survivin-specific immune response in patients who have most aggressive disease, potentially keeping them in remission for longer.
Phase 1 of the trial included 13 patients with multiple myeloma who received one dose of the vaccine 30 days before ASCT and another dose 21 days after the transplant.
Results
The study’s results are promising. Dr. Locke and his team found that the dendritic cell vaccine was tolerated well by patients with only minor adverse reactions. It induced an increase in CD4 T cells in 35% of the group, and an increase in CD8 T cells in 30% of the group. Antibodies against survivin peptides were detected in just two out of 13 patients at baseline, but that number grew to nine out of 13 patients after vaccination and ASCT. All in all, 85% of patients had either a T cell response or an antibody response against survivin.
Seven patients showed an improved clinical response 90 days after transplant, all of which showed a survivin-specific immune response. At the four-year follow-up, six out of the seven patients were alive and disease-free, providing a 71% estimated rate of four-year survival – a significant increase from the historical data that shows just a 50% chance of four-year progression-free survival.
Together with ASCT, this dendritic cell vaccine was associated with long-term disease control, which is excellent news for multiple myeloma patients who may have not reached remission prior to their transplant.
What’s Next
From this study, we’ve found that we can target survivin with a vaccine-based approach to induce an immune response prior to ASCT for multiple myeloma patients. As this strategy is implemented, there is promising potential that it may help improve multiple myeloma patient outcomes.
Looking ahead to the future, Moffitt’s multidisciplinary team of clinicians and researchers hope to see larger, randomized studies to better assess the potential benefits of using the vaccine earlier in the timeline of the disease to prevent more aggressive forms.
Moffitt Cancer Center prides itself in providing various treatment options for multiple myeloma patients beyond the standard of care to give patients the best outcomes and best shot at reaching remission and avoiding returning disease.
The best place for your multiple myeloma patients to be is Moffitt, where we work collaboratively with referring providers to ensure the highest quality care and the most cutting-edge, promising treatments.
If you’d like to refer a patient to Moffitt, complete our online form or contact a physician liaison for assistance. As part of our efforts to shorten referral times as much as possible, online referrals are typically responded to within 24 - 48 hours.