Last week, MMRF held a meeting to hear updates from our Immune Networks of Excellence. This innovative program was initiated in 2018 with the goal of accelerating new immune therapies into the clinic to benefit multiple myeloma patients.
Dr. Ola Landgren of Memorial Sloan Kettering is leading a group of researchers looking into why some patients become resistant to immunomodulatory drugs, for example Revlimid and Pomalyst. This is an important question, as many patients receive Revlimid maintenance therapy, yet eventually relapse as their myeloma cells become resistant to this medication. The team is beginning to tease apart the complicated interactions between a patient’s immune system and their myeloma cells inside the bone marrow, and have found differences in the amount, type, and location of T cells present in patients with long successful MRD negative maintenance therapy vs patients who become MRD positive more quickly after beginning maintenance therapy. This information may someday help doctors predict which patients will relapse more quickly, thereby enabling a more timely switch to another therapy which could be more effective.
Dr. David Avigan of Beth Israel Deaconess Hospital leads a team of researchers who are working to develop a new combination therapy which will utilize both CAR T-cells and a personalized anti-myeloma vaccine. Their first task has been to develop a new CAR T-cell which binds to 2 different targets on the surface of myeloma cells, BCMA and CD38. The researchers have accomplished this goal and found that this new dual-target CAR T was more effective in killing myeloma cells than CAR T-cells that bind to only one target on myeloma cells. In addition, combination therapy with these dual-targeting T cells plus a vaccine worked better to keep mice from getting myeloma, and caused the CAR T-cells to last longer in the mouse bloodstream. If these results hold true in human clinical trials, a treatment of this type could cause CAR T-cell therapy to produce a longer-lasting response in patients; the current length of response to CAR T therapy is about one year. The initial human trials of this experimental combination therapy are already ongoing in a very small number of relapsed/refractory myeloma patients and will soon begin in patients with high risk myeloma.
Dr. Ivan Borrello of Johns Hopkins and his team are making very detailed measurements of what is happening in the bone marrow (T cell numbers and types, levels of immune factors) where myeloma cells grow, and relating these measurements to how well the myeloma cells grow and how well therapies work. In this way, they hope to be able to come up with a numerical “immunoscore” for patients which could one day help predict disease status and response to immunotherapy in individual patients. The team is already making progress in detecting and understanding which T cell populations are associated with better patient outcomes, and will be working to perfect and test their model in scenarios such as predicting which patients may progress from MGUS to SMM to MM, and identifying a high risk myeloma signature.
The immune system, and its interaction with myeloma cells, is incredibly complicated, and much work remains to be done in order to understand this interaction and how it can be utilized to help myeloma patients. These three Immune Networks of Excellence are at the forefront of this type of research in myeloma and their continued success will lead the myeloma community toward more effective therapies or possibly even a cure for myeloma. We look forward to hearing their next update!