Memory-like NK cells after hematopoietic cell transplant to eradicate measurable residual disease
Rizwan Romee
MDDana-Farber Cancer Institute
Project Term: July 1, 2024 - June 30, 2027
Relapse in patients with acute myeloid leukemia (AML) after hematopoietic cell transplant (HCT) is associated with extremely poor prognosis and thus remains a major unmet need. Natural killer (NK) cells are attractive for treating relapse in the post-HCT setting as these cells are not associated with causing graft-versus-host-disease. Cytokine-induced memory-like (CIML or memory-like) NK cells described by our group, demonstrate enhanced anti-leukemia activity, and persist for up to several months in an immune compatible post HCT setting (when derived from the stem cell donor). The goal of this trial is to evaluate donor CIML NK cells early after HCT in AML patients with measurable residual disease (MRD) and therefore otherwise with a high risk of relapse.
Blood cancers including AML are typically treated with chemotherapy followed by stem cell transplant to achieve potential cure. However, relapse after stem cell transplant remains the number one cause of treatment failure in these patients and these patients have extremely poor outcomes (<20% long term survival). Standard therapies, including collecting more donor lymphocytes (T cells) or doing a 2nd transplant have a low chance of success and are often associated with significant risks, including graft-versus-host disease (GVHD). Natural killer (NK) cells are a type of an immune cell that have the ability to attack and destroy blood cancer and have the advantage of not causing GVHD. Cytokine-induced memory-like (CIML) NK cells have all the advantages of NK cells, but in addition can last longer in patients after infusion, are better able to attack and destroy blood cancer cells when compared to conventional NK cells and can further awaken other immune cells like T cells to help eradicate the surviving cancer cells. Initial experience with CIML NK cells to treat relapsed blood cancer, both before and after bone stem cell transplant, has shown they are safe and can put the cancer back into remission in over half of the treated patients. However, all treated patients eventually have their blood cancer come back again, suggesting that CIML NK cells do not destroy all cancer cells especially when the tumor load is high. This clinical trial mainly aims to evaluate the safety and potential efficacy of donor derived (same donor as the stem cell graft) CIML NK cells early after stem cell transplant in patients with AML with otherwise high risk of disease relapse. An additional aim is to learn potential resistance mechanisms in the blood cancer cells which allows them to escape CIML NK cells. These mechanisms, once identified, could lead to new therapies that could be combined with CIML NK cells to make them a very effective tool to prevent and treat relapse of blood cancer including after stem cell transplant.