Effect of bone marrow disease on hematologic toxicity and response to [¹⁷⁷Lu]Lu-PSMA-617 therapy: insights from PSMA-PET/CT imaging

Nuno Borges^{1

2

3}, Meryam Losee⁴, Mofei Liu⁵, Su-Chun Cheng⁵, Arda Könik^{5

6}, Jolivette Ritzer⁵, Andrew Wolanski⁵, Thomas S C Ng^{6

7}, Atish D Choudhury^{5

6}, Mary-Ellen Taplin^{5

6}, Praful Ravi^{5

6}, Heather Jacene^{5

8

6}

Affiliations

¹ Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, USA. nborges2@bwh.harvard.edu.
² Brigham and Women's Hospital, 75 Francis Street, Boston, Boston, MA, USA. nborges2@bwh.harvard.edu.
³ Harvard Medical School, 25 Shattuck Street, Boston, MA, USA. nborges2@bwh.harvard.edu.
⁴ School of Medicine and Health Sciences, George Washington University, 2300 I St NW, Washington, DC, USA.
⁵ Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, USA.
⁶ Harvard Medical School, 25 Shattuck Street, Boston, MA, USA.
⁷ Massachusetts General Hospital, 55 Fruit St, Boston, MA, USA.
⁸ Brigham and Women's Hospital, 75 Francis Street, Boston, Boston, MA, USA.

PMID: 40908334
DOI: 10.1007/s00259-025-07541-3

Effect of bone marrow disease on hematologic toxicity and response to [¹⁷⁷Lu]Lu-PSMA-617 therapy: insights from PSMA-PET/CT imaging

Nuno Borges et al. Eur J Nucl Med Mol Imaging. 2025.

. 2025 Sep 5.

doi: 10.1007/s00259-025-07541-3. Online ahead of print.

Authors

Affiliations

¹ Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, USA. nborges2@bwh.harvard.edu.
² Brigham and Women's Hospital, 75 Francis Street, Boston, Boston, MA, USA. nborges2@bwh.harvard.edu.
³ Harvard Medical School, 25 Shattuck Street, Boston, MA, USA. nborges2@bwh.harvard.edu.
⁴ School of Medicine and Health Sciences, George Washington University, 2300 I St NW, Washington, DC, USA.
⁵ Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, USA.
⁶ Harvard Medical School, 25 Shattuck Street, Boston, MA, USA.
⁷ Massachusetts General Hospital, 55 Fruit St, Boston, MA, USA.
⁸ Brigham and Women's Hospital, 75 Francis Street, Boston, Boston, MA, USA.

PMID: 40908334
DOI: 10.1007/s00259-025-07541-3

Abstract

Purpose: Despite the effectiveness of [¹⁷⁷Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer (mCRPC), hematologic toxicity remains a concern, particularly in patients with bone metastases. This study evaluated whether the extent, intensity, and heterogeneity of bone disease on pretreatment PSMA-PET/CT were associated with hematologic toxicity, PSA response, and overall survival (OS) in mCRPC patients treated with [¹⁷⁷Lu]Lu-PSMA-617.

Methods: This retrospective study included 96 mCRPC patients who underwent pretreatment PSMA-PET/CT and received standard-of-care [¹⁷⁷Lu]Lu-PSMA-617. Hematologic toxicity, PSA responses, and OS were analyzed in relation to quantitative PET parameters, including tumor volume, SUVmean, and heterogeneity of PSMA uptake in bone metastases.

Results: Clinically significant hematologic toxicity occurred in 19 patients (19.8%). Treatment discontinuation was more likely in those with a significantly higher (p = 0.007) percentage of total bone volume with PSMA-avid disease (median 28% vs. 1.7%). Those requiring dose delays or reductions (median 21% vs. 1.5%), blood transfusions (median 21% vs. 1.4%), and platelet transfusions (median 32% vs. 1.8%) also exhibited higher median percentages of total bone volume involvement (all p < 0.01). Patients with more heterogeneous PSMA uptake had lower PSA50 response rates than those with more homogeneous uptake (30.3% vs. 64.5%, p = 0.002). A > 50% difference between PSMA-low and PSMA-high bone disease was associated with significantly shorter OS (p < 0.001).

Conclusion: Extensive PSMA-avid bone involvement was associated with increased hematologic toxicity in mCRPC treated with [¹⁷⁷Lu]Lu-PSMA-617. Greater heterogeneity in PSMA uptake correlated with lower PSA50 response and OS but not hematologic toxicity. Careful patient selection and monitoring are needed, particularly in those with widespread bone disease.

Keywords: Castration-resistant prostate cancer; Heterogeneity; PSA50; PSMA-PET/CT; Post treatment; [177Lu]Lu-PSMA-617.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval: This is a retrospective observational study of data obtained from electronic medical record (EMR) review and an institutional review board-approved prospective database that includes all patients who had PSMA-PET/CT scans and standard-of-care treatment with [177Lu]Lu-PSMA-617 at our institution (DFCI protocol 21–629). The Dana-Farber Harvard Cancer Center IRB waived the requirement for informed written consent. The study was conducted in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments. Financial interests: Atish D Choudhury: Advisory board: Tolmar, Pfizer, Astellas, Janssen, Sanofi Aventis; Research Funding to Institution: Bayer, Pfizer, Eli Lilly, Sumitomo Pharma; Honoraria for speaking engagement: Bayer, Pfizer, Lantheus. Mary-Ellen Taplin: Advisory board: Blue Earth Diagnostics, Novartis. Thomas Ng: Unrelated support from Lantheus and Bayer; Supported in part by U.S. National Institutes of Health (R21EB036323, R01DK097112), U.S. Department of Defense (W81XWH-22-1-0061), and the Lee Family Foundation. Praful Ravi: Research funding to institution: Lilly, Bayer, Telix, Blue Earth Diagnostics, Lantheus, Novartis; Advisory Board – Bayer. Heather Jacene: Research Funding to Institution: Blue Earth Diagnostics, Lantheus; Honoraria: Elsevier, intouchCONGRESS, Monrol, ITM; Consulting: Spectrum Dynamics; Royalties: Cambridge Publishing; Stipend: American Journal of Radiology; Supported in part by U.S. National Institutes of Health (R01CA251803, R01Ca235589). All other authors have no disclosures.

References

1. Bubendorf L, Schopfer A, Wagner U, et al. Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol. 2000;31(5):578–83. https://doi.org/10.1053/hp.2000.6698 . - DOI - PubMed
1. Vogelzang NJ, Coleman RE, Michalski JM, et al. Hematologic safety of radium-223 dichloride: baseline prognostic factors associated with myelosuppression in the ALSYMPCA trial. Clin Genitourin Cancer. 2017;15(1):42–e528. https://doi.org/10.1016/j.clgc.2016.07.027 . - DOI - PubMed
1. Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385(12):1091–103. https://doi.org/10.1056/NEJMoa2107322 . - DOI - PubMed - PMC
1. Fizazi K, Herrmann K, Krause BJ, et al. Health-related quality of life and pain outcomes with [(177)Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24(5):597–610. https://doi.org/10.1016/S1470-2045(23)00158-4 . - DOI - PubMed - PMC
1. Groener D, Nguyen CT, Baumgarten J, et al. Hematologic safety of (177)Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer. EJNMMI Res. 2021;11(1): 61. https://doi.org/10.1186/s13550-021-00805-7 . - DOI - PubMed - PMC

LinkOut - more resources

Full Text Sources
- Springer
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Effect of bone marrow disease on hematologic toxicity and response to [¹⁷⁷Lu]Lu-PSMA-617 therapy: insights from PSMA-PET/CT imaging

Affiliations

Effect of bone marrow disease on hematologic toxicity and response to [¹⁷⁷Lu]Lu-PSMA-617 therapy: insights from PSMA-PET/CT imaging

Authors

Affiliations

Abstract

Conflict of interest statement

References

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous