Results of a small study recently conducted at Johns Hopkins University indicate that Revlimid may boost vaccine responses in multiple myeloma patients.

Based on these results, the researchers who organized the study believe Revlimid could be used as part of a strategy to increase immune responses against both cancer and infectious diseases.

The researchers also argue that Revlimid may help reduce infections in myeloma patients being treated with the drug.  Infections are an important challenge for myeloma patients due to the immune system dysfunction that develops during the course of the disease.

Furthermore, immune-based therapies (such as vaccines) are currently a growing area of development in myeloma research (see related Beacon news).  As such, the Johns Hopkins researchers suggest that the enhanced anti-myeloma responses generated by Revlimid may be beneficial in these therapies.

Revlimid (lenalidomide) is classified as an immunomodulatory agent because it is able to stimulate immune responses and inhibit inflammation.

Previous research has shown that Revlimid can boost immune responses when administered to myeloma patients (see related Beacon news).

Due to the nature of the disease, multiple myeloma has profound effects on the function of the immune system.

When functioning properly, plasma cells produce a variety of infection-fighting proteins called antibodies. In multiple myeloma, however, plasma cells begin overproducing one type of abnormal antibody (M-protein), which cannot effectively fight infections.

The resulting weakening of the immune system can increase the susceptibility of myeloma patient's to infectious diseases, the most common of which are pneumonia, pyelonephritis (inflammation of the kidney), bladder or kidney infections, and sinusitis.

The current guidelines of the International Myeloma Working Group recommend that myeloma patients receive a number of vaccinations to increase protection against these diseases (see related Beacon news).

In this study, the researchers sought to determine whether using Revlimid could further enhance infectious disease vaccine responses in myeloma patients.

In addition, they sought to investigate whether Revlimid boosts the immune response against myeloma cells.

The researchers designed their study to monitor immune responses during Revlimid treatment in two ways.

First, in order to determine whether Revlimid enhances vaccine responses, the researchers administered Revlimid in combination with the vaccine Prevnar.  Prevnar is a vaccine used to prevent disease caused by the bacterium Streptococcus pneumoniae. 

Additionally, they measured Revlimid’s effects on the immune response to myeloma directly by measuring components of the immune system that specifically recognize and destroy cancerous cells.

The study enrolled 22 myeloma patients who had relapsed following one to three prior therapies.  Enrolled patients went one month without myeloma treatment prior to the start of the study.

The patients were divided into two treatment groups.  Patients in both groups received 25 mg of Revlimid daily on days 1 to 21 of a 28-day cycle, for a total of six cycles.  In addition, all patients received two vaccinations with Prevnar.

Patients in the first treatment group received their first Prevnar vaccination two weeks before the start of Revlimid treatment and a second vaccination on day 14 of the second treatment cycle.  Patients in the second group received their first vaccination on day 14 of the second treatment cycle and another vaccination on day 14 of the fourth treatment cycle.

Because steroids such as dexamethasone (Decadron) and prednisone suppress the immune system, patients were not allowed to use steroids during the study.

The researchers measured antibody levels in both patient groups prior to treatment, prior to the second vaccination, and six weeks after the second vaccination.

They found that while the levels of antibody against the Prevnar vaccine were steady or declined in the first treatment group, which received the first vaccination prior to the start of Revlimid treatment, antibodies instead rose for patients in the second group, which had been treated with Revlimid prior to the vaccinations.

Furthermore, researchers also measured the number of specific immune cells, called T cells, generated against the Prevnar vaccine.

They found that, in the first patient group, there was no increase in the number of specific T cells following either the first or second vaccination.  In the second treatment group, however, researchers found that specific T cells increased, with a maximal 4.7-fold increase observed following the first vaccination.

In addition to having a greater number of T cells generated against the Prevnar vaccine, researchers also found that the T cells generated by patients in the second treatment group were superior at protecting against Streptococcus pneumoniae infection than those generated by the first treatment group.

The researchers also measured the immune responses to myeloma cells in patients from both treatment groups.

They found that the myeloma-specific immune response was enhanced in the second treatment group, which had been treated with Revlimid prior to Prevnar vaccination.  In this group, the number of cells specific for the destruction of myeloma cells increased from 2.25 percent to 7.7 percent over the course of treatment.  The first treatment group, however, did not generate a myeloma-specific response.

For more information, please see the study in the journal Clinical Cancer Research (abstract).