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90Y-labeled anti-CD45 antibody allogeneic hematopoietic cell transplantation for high-risk multiple myeloma

Bone Marrow Transplantation volume 56, pages 202–209 (2021)Cite this article

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Abstract

To improve disease control without increasing the toxicity of a reduced-intensity allogeneic hematopoietic cell transplantation (HCT) in multiple myeloma (MM), a phase I trial was performed using an antibody-radionuclide conjugate targeting CD45 (90Y-DOTA-BC8) as conditioning. 90Y-DOTA-BC8 was combined with fludarabine and low-dose TBI followed by allogeneic HCT in patients with MM and ≥1 adverse risk characteristic at diagnosis, relapse after autologous transplant, or plasma cell leukemia (PCL). The primary objective was to estimate the maximum tolerated radiation absorbed dose. Fourteen patients were treated (one with PCL, nine failed prior autologous HCT, and nine with ≥1 adverse cytogenetics). Absorbed doses up to 32 Gy to liver were delivered. No dose-limiting toxicities occurred. Non-hematologic toxicities were manageable and included primarily gastrointestinal (43%) and metabolic/electrolyte disturbances (36%). Treatment-related mortality at 100 days was 0%. At a median follow-up of 5 years, the overall survival was 71% (median not reached) and the progression-free survival was 41% (median 40.9 months). The incorporation of CD45-targeted radioimmunotherapy (RIT) into a reduced-intensity allogeneic HCT is well-tolerated and may induce long-term remissions among patients with poor-risk MM, supporting further development of RIT-augmented conditioning regimens for HCT.

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Fig. 1: Treatment schema.
Fig. 2: Survival outcomes.

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Acknowledgements

This work was supported by grants R21 CA155911, T32 CA009515, R01 CA205248, and P30 CA015704 from the National Institutes of Health, National Cancer Institute and the Conquer Cancer Foundation. The authors thank the patients and family members who enrolled in NCI protocol NCT01503242. We acknowledge the nurses at the University of Washington Medical Center and the Seattle Cancer Care Alliance for clinical care contributions. We also acknowledge Nicholas Brown, Elizabeth Morrigan, and Monina Almeda for assistance with data collection, Kelsey Baker for statistical support, and Nancy Press for assistance with the figures.

Funding

NIH/NCI R21 CA155911, NIH/NCI T32 CA009515, NIH/NCI R01 CA205248, NIH/NCI P30 CA015704, Conquer Cancer Foundation.

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Author notes

  1. These authors contributed equally: William I. Bensinger, Damian J. Green

Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Sherilyn A. Tuazon, Brenda M. Sandmaier, Theodore A. Gooley, Leona A. Holmberg, Pamela S. Becker, Sally J. Lundberg, Johnnie J. Orozco, Ajay K. Gopal, Brian G. Till, David G. Coffey, Margaret E. Nartea, Oliver W. Press & Damian J. Green

  2. Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA, USA

    Sherilyn A. Tuazon, Brenda M. Sandmaier, Leona A. Holmberg, Johnnie J. Orozco, Ajay K. Gopal, Brian G. Till, David G. Coffey, Oliver W. Press & Damian J. Green

  3. Versant Medical Physics and Radiation Safety, Richland, WA, USA

    Darrell R. Fisher

  4. Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA

    Pamela S. Becker

  5. Department of Nuclear Medicine, University of Washington, Seattle, WA, USA

    Manuela C. Matesan & Joseph G. Rajendran

  6. Swedish Cancer Institute, Seattle, WA, USA

    John M. Pagel & William I. Bensinger

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Contributions

S.A.T. collected, analyzed and interpreted data and wrote the manuscript. D.J.G. collected, analyzed and interpreted data and co-wrote the manuscript. W.I.B. collected, analyzed and interpreted data and wrote the clinical trial. O.W.P., J.M.P., T.A.G., J.G.R. and D.R.F. contributed to the conception and design of the study. T.A.G. and D.G.C. analyzed the data. All authors contributed to data interpretation, manuscript editing and, aside from O.W.P.†, approval of the final manuscript.

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Correspondence to Damian J. Green.

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Conflict of interest

BMS reports consulting for Kiadis Pharma, Actinium Pharmaceuticals, Frazier Healthcare Ventures, and Bristol-Meyers Squibb, equity ownership in AnaptysBio, Oncoresponse, Inipharm, EpiThany, and Blaze Bioscience, employment and equity ownership in Mavupharma, Inc., and research funding from Bellicum. LAH reports research funding from Seattle Genetics, Merck, Millennium Pharmaceuticals, Celgene, Sanofi-Aventis, royalties from UpToDate, and consulting for Jazz Pharmaceuticals and the National Comprehensive Cancer Network. JJO receives research funding from Actinium Pharmaceuticals. AKG reports grants and nonfinancial research support from Teva, Bristol-Myers Squibb, Merck, Takeda, Seattle Genetics, Pfizer, Janssen, Takeda, and Effector, and personal fees and nonfinancial support from Seattle Genetics, Pfizer, Janssen, Gilead Sciences, Sanofi-Aventis, Spectrum, Amgen, Aptevo, BRIM bio, Acerta, I-Mab-pharma, Compliment, Asana Bio, and Incyte. BGT holds patents and receives royalties and research funding from Mustang Bio. JMP reports consulting for Actinium Pharmaceuticals, Astrazeneca Pharmaceuticals, Bayer Healthcare Pharmaceuticals, F. Hoffman-La Roche, Pharmacyclics LLC, Teva Pharmaceuticals, consulting and personal fees from Celgene, Gilead Sciences, Janssen, personal fees from Millennium Pharmaceuticals, and honoraria from Seattle Genetics and Spectrum Pharmaceuticals. WIB reports consulting and personal fees from Amgen, Celgene, Janssen and personal fees from Millennium Pharmaceuticals. DJG receives research funding from Juno Therapeutics, Celgene, Merck, Seattle Genetics, Sanofi-Aventis, Cellectar Bio and consults for Cellectar Bio, Celgene, Seattle Genetics, and GSK. The remaining authors have disclosed no conflicts of interest.

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Tuazon, S.A., Sandmaier, B.M., Gooley, T.A. et al. 90Y-labeled anti-CD45 antibody allogeneic hematopoietic cell transplantation for high-risk multiple myeloma. Bone Marrow Transplant 56, 202–209 (2021). https://doi.org/10.1038/s41409-020-01000-3

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