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Optimizing Risk and Response Adaptive Strategies using Immunotherapy in Multiple Myeloma

Saad Usmani

Saad Usmani

MD

Memorial Sloan Kettering Cancer Center

Project Term: July 1, 2017 - June 30, 2022

Despite great improvement in survival outcomes over the last 20 years, multiple myeloma (MM) remains an incurable disease. As anti-myeloma therapeutics continue to expand, it is becoming more crucial to personalize treatment approaches that provide the most value to a specific patient. We are applying this approach in three clinical trials for newly diagnosed MM testing various immunotherapeutic approaches with associated correlative studies. Together, these studies may provide new therapeutic approaches as well as better MRD assessment to better understand a patient’s response.

Lay Abstract

Despite the more than three-fold improvement in survival outcomes over the last 15 years, multiple myeloma (MM) remains an incurable disease. There is growing recognition that MM disease biology is complex and that personalized treatment strategies need to be developed for different MM patients. However, the current MM treatment paradigm is largely based on a patient’s eligibility for a stem cell transplant. Thus, an incredibly heterogeneous disease is being treated in a ‘one-size-fits-all’ way that translates into broad variability in patient outcomes. As anti-myeloma therapeutics continue to expand, it is becoming more crucial to personalize treatment approaches to provide the most value to each individual patient. In addition, it is imperative to complement clinical trials with development of prognostic and predictive biomarkers. Prognostic biomarkers provide the likely natural course of MM in an untreated patient, while predictive biomarkers identify the subpopulation of patients who have better outcomes with specific treatment strategies. Over the last decade, researchers have explored new prognostic biomarkers, such as imaging (PET-CT) as well as assays that test for minimal residual disease (MRD), which is the small number of tumor cells that may remain after treatment. However, their utility as predictive biomarkers is not well established. The overarching aim of this proposal is to investigate risk- and response-adaptive clinical trial strategies for newly diagnosed MM while exploring the predictive role of these biomarkers. We will apply this approach in three clinical trials for newly diagnosed MM. The first two trials compare various combinations of immunotherapeutic agents with current regimens. The first trial examines MRD assays and PET-CT as predictive biomarkers. The second trial assesses MRD to determine the need for transplant and maintenance. The third trial examines the effectiveness of the immunotherapeutic antibody Daratumumab in clearing the bone marrow of residual tumor cells before stem cell collection and transplant in MM patients having a less than ideal response to induction chemotherapy. Together, these studies may provide new therapeutic approaches and improve MRD assessment to better understand a patient’s response. These practice-changing strategies will help move the MM field towards personalized care.

Program
Career Development Program
Grant Subprogram
Scholar in Clinical Research
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