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Clinical Trial
. 2021 Jan;56(1):202-209.
doi: 10.1038/s41409-020-01000-3. Epub 2020 Jul 24.

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

Sherilyn A Tuazon  1   2 , Brenda M Sandmaier  1   2 , Theodore A Gooley  1 , Darrell R Fisher  3 , Leona A Holmberg  1   2 , Pamela S Becker  1   4 , Sally J Lundberg  1 , Johnnie J Orozco  1   2 , Ajay K Gopal  1   2 , Brian G Till  1   2 , David G Coffey  1   2 , Margaret E Nartea  1 , Manuela C Matesan  5 , John M Pagel  6 , Joseph G Rajendran  5 , Oliver W Press  1   2 , William I Bensinger #  6 , Damian J Green #  7   8
Affiliations
Clinical Trial

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

Sherilyn A Tuazon et al. Bone Marrow Transplant. 2021 Jan.

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.

Trial registration: ClinicalTrials.gov NCT01503242.

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Figures

Fig 1.
Fig 1.. Treatment schema.
Dosimetry was performed using 111In-DOTA-BC8 infusion followed by gamma camera imaging at 4 timepoints over the course of 5 days and a bone marrow (BM) biopsy was obtained ~24 hours after infusion of 111In-DOTA-BC8. On approximately day −12, 90Y-anti-CD45 antibody was administered followed by fludarabine (30 mg/m2/day) on days −4, −3 and −2, then total body irradiation (TBI; 2 Gy) and allogeneic peripheral blood stem cell transplant (PBSCT) on day 0. Cyclosporine and mycophenolate mofetil (MMF) were started on day −3 and 0, respectively.
Fig 2.
Fig 2.
Progression-free and overall survival of patients after allogeneic HCT with 90Y-DOTA-BC8 reduced intensity conditioning.
See this image and copyright information in PMC

References

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