Radioimmunotherapy in combination with reduced-intensity conditioning for allogeneic hematopoietic cell transplantation in patients with advanced multiple myeloma

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 MM patients, most of them heavily pretreated including various therapies with proteasome inhibitors, immunomodulatory drugs, anti CD38 antibodies, and autologous hematopoietic cell transplantation (auto-HCT), were treated with a RIT-RIC combination prior to 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) was applied to the bone marrow. After a median follow-up time for surviving patients of 2.1 years (IQR 1.3–3.0), the two-year progression-free survival and overall survival rates were 43 % (95% CI 26–73%) and 55 % (95% CI 38–79), respectively. The two-year non-relapse mortality and cumulative incidence of progression were 17% (95% CI 3–30%) and 46 % (95% CI 25–67%), respectively. Renal toxicity and mucositis were the most frequently observed extramedullary side effects. In conclusion, the addition of RIT to RIC was safe and feasible, and resulted in promising outcomes compared to those previously reported for RIC-based allo-HCT-treated relapsed/refractory MM patients without RIT addition. Nevertheless, in spite of RIT addition, relapse after allo-HCT remained a major determinant of therapeutic failure. Therefore, development of novel RIT strategies (e.g., dual targeting strategies or combinations with adapter chimeric antigen receptor T cell-based therapies) are warranted.