Radioimmunotherapy in Combination with Reduced-Intensity Conditioning for Allogeneic Hematopoietic Cell Transplantation in Patients with Advanced Multiple Myeloma

Frederick Fasslrinner; Friedrich Stölzel; Michael Kramer; Raphael Teipel; Claudia Brogsitter; Anke Morgner; Claudia Arndt; Michael Bachmann; Mathias Hänel; Christoph Röllig; Jörg Kotzerke; Johannes Schetelig; Martin Bornhäuser

doi:10.1016/j.bbmt.2019.11.007

Radioimmunotherapy in Combination with Reduced-Intensity Conditioning for Allogeneic Hematopoietic Cell Transplantation in Patients with Advanced Multiple Myeloma

Biol Blood Marrow Transplant. 2020 Apr;26(4):691-697. doi: 10.1016/j.bbmt.2019.11.007. Epub 2019 Nov 12.

Affiliations

¹ Medical Clinic and Polyclinic I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. Electronic address: [email protected].
² Medical Clinic and Polyclinic I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
³ Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁴ Department of Medicine III, Klinikum Chemnitz, Chemnitz, Germany.
⁵ Helmholtz-Zentrum Dresden-Rossendorf, Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.
⁶ Helmholtz-Zentrum Dresden-Rossendorf, Department of Radioimmunology, Institute of Radiopharmaceutical Cancer Research, Dresden, Germany; German Cancer Consortium, partner site Dresden, Germany, and German Cancer Research Center, Heidelberg, Germany; National Center for Tumor Diseases, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁷ Medical Clinic and Polyclinic I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; German Cancer Consortium, partner site Dresden, Germany, and German Cancer Research Center, Heidelberg, Germany; National Center for Tumor Diseases, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁸ Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; German Cancer Consortium, partner site Dresden, Germany, and German Cancer Research Center, Heidelberg, Germany; National Center for Tumor Diseases, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

PMID: 31730919
DOI: 10.1016/j.bbmt.2019.11.007

Abstract

Radioimmunotherapy (RIT) has the potential to reduce the incidence of relapse after allogeneic hematopoietic cell transplantation (allo-HCT) in patients with advanced-stage multiple myeloma (MM). In this study, we evaluated the efficacy of RIT in combination with chemotherapy-based reduced-intensity conditioning (RIC). RIT was based on the coupling of an anti-CD66 antibody to the beta emitter 188-rhenium (188-re) for targeted bone marrow irradiation. Between 2012 and 2018, 30 patients with MM, most of them heavily pretreated with various therapies including proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies, and autologous hematopoietic cell transplantation (auto-HCT), were treated with a RIT-RIC combination before allo-HCT. In addition to a fludarabine plus melphalan- or treosulfan-based RIC, a median dose of 18.1 Gy (interquartile range [IQR], 14.6 to 24.1 Gy) was applied to the bone marrow. After a median duration of follow-up for surviving patients of 2.1 years (IQR, 1.3 to 3.0 years), the 2-year progression-free survival and overall survival rates were 43% (95% confidence interval [CI], 26% to 73%) and 55% (95% CI, 38% to 79%), respectively. The 2-year nonrelapse mortality and cumulative incidence of progression were 17% (95% CI, 3% to 30%) and 46% (95% CI, 25% to 67%), respectively. Renal toxicity and mucositis were the most frequent extramedullary side effects. In conclusion, the addition of RIT to RIC was safe and feasible and resulted in promising outcomes compared with those previously reported for RIC-based allo-HCT without the addition of RIT in patients with relapsed/refractory MM. Nevertheless, despite the addition of RIT, relapse after allo-HCT remained a major determinant of therapeutic failure. Therefore, the development of novel RIT strategies (eg, dual targeting strategies or combinations with adapter chimeric antigen receptor T cell-based therapies) is needed.

Keywords: Allogeneic hematopoietic cell transplantation; CD66; Multiple myeloma; Radioimmunotherapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Hematopoietic Stem Cell Transplantation*
Humans
Multiple Myeloma* / therapy
Neoplasm Recurrence, Local
Radioimmunotherapy
Transplantation Conditioning
Transplantation, Homologous