Clinical Trial: A Personalized Vaccine in Smoldering Myeloma at MD Anderson Cancer Center

Many approaches are attempting to prevent smoldering myeloma from progressing to active myeloma. One such approach is a personalized vaccine being developed at MD Anderson Cancer Center.

A trial of 30 patients (with 20 patients currently in the study) aims to create a personalized vaccine from the patient's own bone marrow sample. The content of the vaccine are peptides (short proteins) which are derived from the bioinformatics analysis of genetic sequencing of each patient's individual myeloma. The vaccine product is subject to high manufacturing standards that are guided by the FDA. Each vaccine takes about 3 months to produce after the bone marrow biopsy is performed and the vaccine is ready to be administered. The study is being run by Elisabet Manasanch, MD of MD Anderson Cancer Center. 

In Stage I of the study, patients undergo collection of blood and bone marrow to make the vaccine. After the vaccine has been developed, the personalized vaccine is given as a subcutaneous shot eight times in total: every other week for the first two months and then monthly for months 3-6 if there is no disease progression or unacceptable toxicity.

In Stage II of the study, the vaccine is combined with lenalidomide, a well known drug in multiple myeloma care that boosts the immune system. Patients undergo collection of blood and bone marrow to make the vaccine. Similarly, they receive the subcutaneous shot eight times in total: every other week for the first two months and then monthly for months 3-6 if there is no disease progression or unacceptable toxicity.

This study aims to prove that such a personalized vaccine can work in smoldering myeloma. Success will be determined by the proportion of patients for whom the vaccine can be successfully developed, taking note of any major side effects. 

Researchers are also watching study results to determine: 

• How long T cell responses last to the vaccine
• Time to progression from smoldering myeloma to active myeloma
• Duration of response
• Clinical benefit rate
• Overall survival
• MRD status
• Immune system reactions such as dendritic cells, T and B cells, natural killer (NK)- and NKT-cells, and inhibitory/activation markers on tumor cells at baseline  and during the trial

Patients can join if they have intermediate or high-risk smoldering multiple myeloma that includes at least one of the following risk factors:

• Greater than or equal to 95% abnormal plasma cells/total plasma cells in bone marrow compartment. (This is measured as a percentage of the total abnormal versus normal plasma cells in the bone marrow using standard flow cytometry of the bone marrow aspirate.
• Low uninvolved immunoglobullins (for example, if a patient has IgA smoldering multiple myeloma, then either having a low IgM and/or low IgG will qualify as a risk factor for progression to multiple myeloma) 

Patients cannot have myeloma-defining events or amyloidosis. Patients cannot be on steroids or have received chemotherapy agents approved for myeloma treatment.