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 ¿MRD400 status (400-fold minimal residual
disease (MRD) depletion over 4 months) to validate ¿MRD400 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
¿MRD400 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.