# Integration of single cell sequencing as a biomarker of PARP inhibitor response for IDH1 and IDH2 mutated AML and MDS

> **NIH NIH UM1** · YALE UNIVERSITY · 2021 · $123,583

## Abstract

Project Summary/Abstract
Meningioma is the most common intracranial tumor and affects approximately 150,000
individuals in the USA. Approximately 10-20% of them will eventually develop recurrent disease
despite standard surgery and radiation therapy (RT). There is currently no effective salvage
therapy for radiation-relapsed meningioma. Preclinical models suggest possible synergy when
immune checkpoint inhibitors of the programmed-death-1 (PD-1) and cytotoxic T-lymphocyte-
associated protein 4 (CTLA-4) pathways are administered with concurrent RT, and anti-PD-1
inhibitor has shown promising activity against meningioma in cases reports. The ETCTN 10186
study is a phase I/II study that evaluates the safety and efficacy of combining anti-PD-1 and
anti-CTLA-4 inhibitors with multi-fraction stereotactic radiosurgery for radiation-relapsed high-
grade meningioma. Although predictive biomarkers for immunotherapy response have not been
well established, specific T-cells or myeloid cells in peripheral blood have shown correlations
with the treatment response to anti-PD-1 or anti-CTLA-4 inhibitors in previous clinical trials for
solid tumors. The objective of the proposed study is to leverage the blood samples collected in
the ETCTN study to discover potential biomarkers to predict immunotherapy response. The
specific aim is to determine if peripheral T-cell or myeloid dynamics as assessed using
multiparameter flow cytometry would correlate with treatment response. Twelve patients have
already been enrolled in the ongoing ETCTN study, and their peripheral blood mononuclear
cells (PBMCs) at baseline and weeks 4 and week 12 during treatment have been centrally
processed and cryopreserved. These PBMC samples will be analyzed by multiparameter flow
cytometry to evaluate the phenotype changes of peripheral T-cells and myeloid cells during
treatment. The changes over time and the correlation with radiological response will be
examined to generate candidate peripheral blood biomarkers for further development and
validation. Once specific candidate phenotypes are identified, the reproducibility of quantifying
these cellular subsets using flow cytometry will also be evaluated.

## Key facts

- **NIH application ID:** 10337798
- **Project number:** 3UM1CA186689-06S1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Patricia M. LoRusso
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $123,583
- **Award type:** 3
- **Project period:** 2021-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10337798

## Citation

> US National Institutes of Health, RePORTER application 10337798, Integration of single cell sequencing as a biomarker of PARP inhibitor response for IDH1 and IDH2 mutated AML and MDS (3UM1CA186689-06S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10337798. Licensed CC0.

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