This article is the third in a five-part series about emerging vaccines for multiple myeloma. It describes vaccines for which clinical trials have been completed. The first article ^[1] in the series provides an introduction to the concept of a myeloma vaccine, and the second article ^[2] provides an introduction to the various types of myeloma vaccines that are currently under development. The fourth article ^[3] focuses on ongoing vaccine research, and the fifth article ^[4] tells the story of a patient who participated in a myeloma vaccine clinical trial.

Clinical trials for various myeloma vaccines have been completed within the last several years. The following is a summary of the most recently reported results from completed clinical trials for multiple myeloma vaccines, starting with the most promising results.

Phase 2 Clinical Trial Shows Cell-Based Antibody Fragment Myeloma Vaccine Improves Survival

In October 2009, researchers at the Mayo Clinic in Rochester, Minnesota, reported the results of a Phase 2 myeloma vaccine trial. According to their findings, a vaccine developed from the cells of myeloma patients was associated with prolonged survival.

Patients were immunized with unique fragments created from their monoclonal (M)-protein combined with cells that activate the immune system.

This trial was conducted in patients directly following autologous stem cell transplantation. A total of 27 patients were given the vaccine, 17 of whom were relapsed/refractory and 10 of whom were in a response or plateau phase.

Responses in patients receiving the vaccine were compared to 124 patients who underwent stem cell transplantation without vaccination.

To qualify for the trial, patients had to have quantifiable M-protein present in the serum, which was frozen and stored for vaccine preparation prior to stem cell transplantation.

Myeloma patients were vaccinated intravenously with their unique M-protein/immune cell vaccine in weeks 0, 2, 4, and 16 following their stem cell transplants.

Ninety-six percent of patients achieved an objective response following stem cell transplantation. Following vaccination, 22 percent of patients achieved improvement to complete response, and 7 percent improved to partial response. The remaining patients experienced prolonged stabilized disease.

There was no statistical difference in time-to-progression or progression-free survival between patients who received the vaccine and those who did not. Overall survival, however, of 5.3 years for patients receiving the vaccine was significantly better than overall survival of 3.4 years for patients who did not receive the vaccine.

For more information, please see the research article in the American Journal of Hematology ^[5] (abstract).

Phase 1 Trial Shows Treatment With Natural Killer Cells From A Related Donor Can Cause Complete Remission

In December 2008, researchers at the Myeloma Institute for Research and Therapy in Arkansas, lead by Dr. Frits van Rhee, published results from a Phase 1 trial investigating another type of cell-based therapy for high-risk or relapsed multiple myeloma.

According to Susann Szmania, a researcher involved in the study, once this type of therapy has been proven effective in the high-risk disease setting, it could be used as an upfront therapy for multiple myeloma patients.  She also noted that it would be a useful addition to stem cell transplantation and/or novel therapies.

To generate anti-myeloma responses in patients, researchers collected natural killer cells from a family member of each participant and used these cells to vaccinate the myeloma patients. Natural killer cells are one part of the immune system primarily responsible for defense against viral infection. However, they can also recognize and kill tumor cells.

Ten patients with relapsed multiple myeloma after single or double autologous stem cell transplantation were enrolled in the study.  Patients were treated with chemotherapy, and then the natural killer cells were administered over two days.  Two weeks later, the patients underwent another autologous stem cell transplant.

Researchers found that 50 percent of study participants achieved complete remission or near complete remission.  The researchers noted that the complete response rate in their study was better than a 40 percent complete response rate seen in a similar group of patients who did not receive natural killer cells, but the results were not statistically different.

No patients experienced graft-versus-host disease, which is a serious side effect associated with stem cell transplants using cells from a donor.

In email correspondence with The Beacon, Ms. Szmania revealed that a similar Phase 2 study has recently been activated.  The trial, designed by Dr. van Rhee and led by Dr. Bijay Nair, will enroll 30 patients over the next 3 years.

For more information on the results of the Phase 1 trial, see the study in the British Journal of Haematology ^[6] (abstract).

Phase 1/2 Clinical Trial Of Cell-Based Antibody Fragment Vaccine Can Stabilize Myeloma

In October 2007, researchers in Italy reported the results of a Phase 1/2 clinical trial that demonstrated a myeloma vaccine was safe and produced an anti-myeloma immune response.

The vaccine was created by combining unique fragments created from each patient’s M-protein with dendritic cells, a type of cell responsible for activating the immune system.

Myeloma patients were enrolled in the trial if, following double stem cell transplantation, they could not tolerate maintenance therapy or progressed during maintenance therapy.

A total of 15 symptomatic multiple myeloma patients were enrolled in the trial. The patients received five injections of the vaccine at two week intervals. If stable disease was achieved and enough vaccine was available, monthly injections were continued.

Following immunization, one patient achieved partial remission after 40 months. Seven patients had stable disease after an average follow-up of 26 months, and seven patients progressed.

For more information, see the research article in the British Journal of Haematology ^[7] (abstract)

Phase 1 Trial Shows Cell-Based Vaccine Can Stabilize Myeloma

In October 2010, researchers from Beth Isreael Deaconess Medical Center and Dana Farber Cancer Institute published results of a Phase 1 trial demonstrating that a multiple myeloma vaccine produced disease stabilization in the majority of enrolled myeloma patients with advanced disease (see related Beacon ^[8] news).

The researchers designed an anti-myeloma vaccine by combining myeloma tumor cells with dendritic cells, a type of cell that helps activate the immune system. When administered to patients, the vaccine stimulates the immune system to form a response against the tumor cells.

A total of 18 multiple myeloma patients were enrolled. After vaccination, 61 percent of patients achieved stable disease.  The longest duration of ongoing stable disease without evidence of progression was 41 months.

The vaccine was well tolerated and did not result in decreased blood cell counts or autoimmunity, a condition in which the patient’s immune system attacks the patient’s own cells and tissues. The most common side effects were redness and pain at the vaccine injection site.

The researchers suggested future trials investigate the use of the vaccine in multiple myeloma patients who undergo vaccination soon after stem cell transplantation.

For more information, please see the article in the journal Blood ^[9] (abstract).

Phase 1/2 Clinical Trial Shows Myeloma Vaccination Regimen Is Ineffective And Poorly Tolerated

In October 2010, researchers at the University of Maryland reported the results of a Phase 1/2 clinical trial demonstrating that a complex myeloma vaccination regimen was not as effective or safe as autologous stem cell transplantation followed by maintenance therapy.

A total of 56 myeloma patients were enrolled in the study.  Patients were divided into two groups; one group received the myeloma vaccine prior to stem cell transplantation, while the other only underwent transplantation.

Prior to stem cell transplantation, half of the patients received a series of myeloma vaccinations comprised of the human telomerase reverse transcriptase (hTERT) and survivin proteins, which are overproduced in myeloma cells.

Those patients’ white blood cells were then collected and activated to divide so they would have more immune cells to specifically target hTERT and survivin.  Two days after stem cell transplantation, the white blood cells were injected into patients.

Researchers found patients who were vaccinated had inferior event-free survival compared to those patients who did not receive vaccination, with 25 percent and 65 percent, respectively, predicted to be event free at two years.  Furthermore, there was no statistical difference in the overall survival between groups.

Researchers attributed the inferior event-free survival in the vaccinated group to decreased use of maintenance therapy following transplantation rather than the myeloma vaccine.

Additionally, patients who received the myeloma vaccinations were at increased risk for developing diarrhea, possibly due to an immune reaction in the colon following vaccination.

For more information, please see the research article in Blood ^[10] (abstract).