Breakthrough in Immunotherapy and Myeloma Prevention

The third week in October found us listening to exciting updates from two of our research initiatives, the Immunotherapy Initiative, and the Prevention Project, funded in collaboration with the Perelman Family Foundation. Multiple principle investigators from each Initiative gathered in the MMRF offices in Norwalk CT to report on research progress seen over the past six months.

Updates from the Immunotherapy Initiative:

  • Network of Dr. David Avigan, Beth Israel Deaconess Medical Center
    • CAR-T cells that recognize two proteins on the surface of myeloma cells (BCMA plus CD38) is more effective at killing myeloma cells than CAR T cells that recognize only BCMA.
    • Vaccines combining both cancer cells and immune cells can stimulate the immune cells and improve their ability to recognize myeloma cells and kill them.
    • immune markers may be able to identify the patients that respond to vaccine therapy best, and patients that can maintain a longer remission.

This combination of CAR T cells with cellular vaccines holds great promise as a therapy for myeloma.

  • Network of Dr. Ivan Borrello, Johns Hopkins Kimmel Cancer Center
    • Dr. Borrello’s research network is characterizing the effects of bone marrow microenvironment on disease progression and response to therapy. Next steps will focus on
      • defining differences between healthy volunteers, MGUS (monoclonal gammopathy of unknown significance)  patients, SMM (smoldering multiple myeloma) patients,, and myeloma patients with active, symptomatic disease.
      • Patients are given a numerical Immunoscore which will reflect the status of each patient’s immune system and help predict which patients will respond best to specific immune therapies and which patients may be resistant to therapies.
  • Network of Dr. Ola Landgren, Memorial Sloan Kettering Cancer Center
    • The network is developing a pipeline of cutting-edge tests designed to uncover how a patient’s myeloma and immune cells respond to immunotherapy, with the goal of identifying ways to check both response and toxicity.
    • This network is building a highly collaborative approach to sharing very limited patient samples across multiple research sites for analysis. The data from these studies will be shared amongst research sites for correlative studies.

Updates from the Prevention Project

  • Dr. Irene Ghobrial team, Dana Farber Cancer Institute:
    • The team has identified several markers in MGUS/SMM patients, including  mutations in the MYC gene, the MAPK gene, and NF-kappaB pathways which may indicate that patients who have these markers are at greater risk of progression to MM.
    • A comparison of using current blood sampling methods to follow disease in SMM patients showed that results based either on cell-free DNA or circulating tumor cells alone are not sufficient when compared to standard bone marrow biopsy results. More advanced approaches combining both methods are needed for the most accurate determination of disease burden.
  • Dr. Ola Landgren team, Memorial Sloan Kettering Cancer Center:
    • Targeted sequencing is an effective and sensitive approach to assess translocations and chromosomal gains and losses in MM. There are ongoing efforts to implement sequencing-based assays to replace cytogenetics (or FISH) in the clinical setting, to provide more accurate results and better define myeloma subtype, which is a critical part of precision medicine.