Predictive markers for personalized therapy in chronic lymphocytic leukemia

PROJECT SUMMARY/ABSTRACT Candidate. Jacob D. Soumerai, MD is an Assistant Professor of Medicine at Harvard Medical School (HMS) and Hematologist/Medical Oncologist at Massachusetts General Hospital (MGH) who conducts mentored clinical research in lymphoma and chronic lymphocytic leukemia (CLL). His goal over the next 5 years is to transition to an R01-funded, independent investigator leading a clinical trials and translational biomarker research program that advances the care of patients with lymphoma/CLL. Mentorship, Career Development, and Training Activities. To ensure his successful transition to independence, Dr. Soumerai developed a robust career development plan to address his training gaps through focused training/coursework and mentoring. His mentors are world-renowned experts in lymphoma and CLL with non-overlapping technical expertise directly related to Dr. Soumerai’s proposed K08 research plan and career objectives, and include Jeremy Abramson MD, Timothy Graubert MD and Andrew Zelenetz MD, PhD. Dr. Soumerai’s K08 career development plan will provide necessary training in translational biomarker assay development, advanced biostatistical techniques for biomarker research, regulatory requirements/procedures and clinical utility evaluation to develop validated biomarkers for clinical use. Research. Validated predictive markers for response are needed to develop personalized therapies and ultimately to improve the health and survival of people living with CLL. His central goal is to identify clinically validated predictive markers for response that help guide development of personalized CLL therapies. To achieve this goal, he will use his co-mentor’s trial of BCL2 inhibitor (BCL2i)-based therapy, which modifies therapy duration based on ΔMRD400 status (400-fold minimal residual disease (MRD) depletion over 4 months) to validate ΔMRD400 as a predictive marker to guide treatment duration to achieve undetectable MRD (uMRD) and identify high-risk patients (Aim 1). Next, he will use BCL2i retreatment efficacy data from his co-mentor’s trial to determine if ΔMRD400 status with prior BCL2i therapy, BALL risk factors for survival (B2-microglobulin, Anemia, LDH, time from Last therapy), or TP53 mutation/17p deletion can predict BCL2i retreatment success/failure (Aim 2). Finally, he will subject serial baseline/on-treatment patient samples from his co-mentor’s trial to PhasED-Seq/CAPP-Seq to identify genomic signatures that predict for failure to achieve uMRD, which might identify therapeutic vulnerabilities leading to novel therapeutic approaches (Aim 3). Completion of this proposal/training plan will position Dr. Soumerai with the necessary experience and skills to become an R01-funded independent investigator leading a clinical trials/translational biomarker research program in lymphoma/CLL.