# Preventing Myeloma Relapse after Autologous Stem Cell Transplantation with Decoy Resistant IL-18

> **NIH NIH U01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2021 · $165,584

## Abstract

Abstract
Multiple myeloma is the second most common hematological malignancy and despite improved patient
outcomes in the era of novel agents, it remains largely incurable. Clinical studies show that autologous stem cell
transplantation (ASCT) remains an efficacious consolidation treatment for eligible patients and a subset of
transplant recipients achieve long-term control of disease. Currently, the prolongation of plateau-phase induced
by ASCT is attributed to the use of myeloablative chemotherapy and cytoreduction. However, ASCT generates
inflammation and profound lymphodepletion, whilst disrupting the marrow microenvironment, all of which has the
potential to induce anti-myeloma immunity. We have recently utilized novel preclinical models to provide
definitive evidence that ASCT invokes myeloma-specific T cell immunity and the re-establishment of a state of
immune equilibrium. Furthermore, we have demonstrated that disease progression after ASCT in these systems
is a result of CD8 T cell exhaustion that is dependent on the accumulation of myeloid suppressive populations
and the expression of multiple checkpoint molecules by CD8 T cells. These inhibitory pathways are highly
amenable to immunotherapeutic approaches after ASCT that invoke long term survival. This proposal will utilize
sophisticated protein and transcriptional based approaches to examine the relationship of T cell function in the
peri-transplant period to subsequent survival and disease control in well-annotated clinical cohorts. A major focus
will be the optimization of innovative immunotherapy approaches after ASCT in preclinical systems for clinical
translation.

## Key facts

- **NIH application ID:** 10286958
- **Project number:** 3U01CA244291-01S1
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Geoffrey Roger HILL
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $165,584
- **Award type:** 3
- **Project period:** 2021-03-11 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10286958

## Citation

> US National Institutes of Health, RePORTER application 10286958, Preventing Myeloma Relapse after Autologous Stem Cell Transplantation with Decoy Resistant IL-18 (3U01CA244291-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10286958. Licensed CC0.

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