Genomic and Immunomic Mechanisms of Resistance During Daratumumab Post Stem Cell Transplantation in Patients with Poor-Risk T-Cell Lymphoblastic Lymphoma/Leukemia
Abstract
Fiscal Year 2022 (FY22) Peer Reviewed Cancer Research Program (PRCRP) Topic Areas and Military Health Focus Area Addressed: This proposal addresses the topic areas of lymphoma and blood cancers with a focus on poor risk T-cell lymphoblastic lymphoma/T-cell acute lymphoblastic leukemia. It addresses the military health areas of mission readiness and health and well-being of military members, Veterans, their beneficiaries, and the general public by specifically addressing the areas of early detection/diagnosis, prognosis, and treatment of pediatric, adolescent, and young adults (PAYA) with T-cell acute lymphoblastic lymphoma and leukemia (T-LL/ALL). Scientific Objective and Rationale: T-LL/ALL is a cancer of white blood cells. It is most common in children, adolescents, and young adults. We cure most patients with T-LL/ALL with very strong chemotherapy. Unfortunately, we do not cure everyone. Patients with T-LL/ALL who do not respond to therapy or who have their disease return (relapse) are very hard to cure. Because their cancer cells do not respond to chemotherapy, new approaches are needed. A bone marrow transplant (BMT) can cure some children and young adults who relapse. But even after transplant, over half of patients (1 in 2) die from T-LL/ALL. To improve cures, we have launched a national clinical trial that combines BMT with a new medicine called Daratumumab. Daratumumab is not a chemotherapy drug. Daratumumab is an immunotherapy drug. Immunotherapies act like the parts of our body that fight infection. Our immune system is supposed to fight cancer cells too, but sometimes it needs help. This grant will study blood, bone marrow, spinal fluid, and tumor samples from patients enrolled on the trial. The major goal is to understand why some patients respond to treatment and why others do not. This will allow us to develop new therapies. We will use very special and advanced tools to study the cancer cells. It will help us identify which patients with T-LL/ALL may respond very well to BMT and immunotherapy. Our hope is to develop blood tests that can predict which patients will relapse. Then we can use these tests in future patients to prevent relapse. Ultimately, we hope to cure more patients with T-LL/ALL. Impact and Ultimate Applicability: T-LL/ALL can affect all people, but it is more common in Black children and young adults. This study will benefit children and adults from all racial and ethnic backgrounds. The studies will help us understand why some patients with T-LL/ALL are not cured with chemotherapy. We can then develop blood tests to predict which patients are likely to fail traditional therapy before they do. We can then treat them with new therapies like the ones studied on our clinical trial. By understanding why some children do and do not respond to chemotherapy, we can develop new medicines and treatments. FY22 PRCRP Overarching Challenges Addressed: (1) Develop innovative prevention strategies and early detection methods to decrease cancer burden in diverse different populations. (2) Identify strategies to predict treatment resistance, recurrence, and the development of advanced disease. (3) Develop and improve minimally invasive methods to detect cancer initiation, recurrence, and progression. (4) Transform cancer treatment through the identification of new targets, especially for advanced disease (T-LL/ALL) and metastasis. (5) Advance immunotherapy across different PRCRP Topic Areas (Daratumumab in lymphoma and blood cancers). (6) Improve prevention strategies, diagnosis, treatment, and outcomes for patients in underserved or under recognized populations (e.g., military populations, rural populations, communities of color, other minorities, and women). The results of our studies will lead to changes in both up-front and relapse diagnosis and treatment of T-LL/ALL and enhance the survival rate across all patient populations. Relevance to Military Health
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310686
Entities
People
- Mitchell S Cairo
Organizations
- New York Medical College
- United States Army