# Project 3: Integrating Plasma Cell-Specific Radioimmunotherapy into Allogeneic Stem Cell Transplantation for Myeloma

> **NIH NIH P01** · FRED HUTCHINSON CANCER CENTER · 2021 · $241,565

## Abstract

PROJECT SUMMARY / ABSTRACT – Project 3
The majority of patients with multiple myeloma (MM) ultimately die of progressive disease despite high rates of
initial response to novel agents. Recent advances allow patients with standard-risk MM to anticipate a median
survival of over 7 years from diagnosis, however those with high-risk disease features continue to experience
early relapse and death. Although autologous hematopoietic cell transplant (HCT) remains a standard of care,
this intervention does not ameliorate the differences in outcome predicted by pre-HCT risk features. In contrast,
responses observed after allogeneic HCT cannot be predetermined by high-risk features. Myeloablative
conditioning regimens, in concert with a graft-versus-myeloma effect, have cured some patients with MM, but
the accompanying toxicity and high rates of non-relapse mortality (NRM) have limited wide adoption. To minimize
the risk of NRM associated with high-intensity preparative regimens, reduced-intensity conditioning (RIC)
regimens have been introduced. Relapse after RIC however, remains the leading cause of death, and measures
that can safely improve the efficacy of the conditioning regimen should be explored. The radio-sensitivity of
malignant plasma cells has been well documented, and the poor prognosis associated with high-risk marrow
cytogenetics is not predictive of response to radiation therapy. CD38 antigen-targeting with α-emitter
radioimmunotherapy (RIT) can eliminate disease in pre-clinical MM models. Based on the physical
characteristics of α-emitting radionuclides and new opportunities to harness their potential, there is a compelling
rationale for employing α-emitter RIT to treat MM. The α-emitter astatine-211 ( 211At) deposits a very large amount
of energy (~100 keV/μm) within a few cell diameters (50-90 μm) resulting in irreparable double strand DNA
breaks that overwhelm cellular repair mechanisms. The purpose of this application is to integrate α-emitter RIT
targeting CD38 (211At-OKT10-B10) into allogeneic HCT conditioning to improve outcomes without increasing
toxicity and NRM. The project will address three hypotheses: 1). 211At-OKT10-B10 will be safe and well tolerated
when integrated into an allogeneic HCT conditioning regimen 2). 211At-OKT10-B10 will selectively target all
malignant plasma cells irrespective of mutational status, 3). B cell maturation antigen (BCMA) targeting with
211At-BCMA-B10 will represent a further refinement to targeting that will demonstrate efficacy in preclinical mouse
models.

## Key facts

- **NIH application ID:** 10601302
- **Project number:** 6P01CA078902-24
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Damian J. Green
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $241,565
- **Award type:** 6
- **Project period:** 1999-04-12 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10601302

## Citation

> US National Institutes of Health, RePORTER application 10601302, Project 3: Integrating Plasma Cell-Specific Radioimmunotherapy into Allogeneic Stem Cell Transplantation for Myeloma (6P01CA078902-24). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10601302. Licensed CC0.

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