The SIERRA trial is a prospective, randomized phase 3 trial in older patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). The hypothesis was that a targeted delivery of radiation to the bone marrow, achieved with a limit of 24-Gy radiation dose to the liver (through an infusion of a therapeutic dose of iodine-131-apamistamab [Iomab-B]), would facilitate successful engraftment despite active disease in the marrow.
Patients eligible for this study were aged ≥55 years with active R/R AML (≥5% blasts), sufficient organ function, and related/unrelated 8/8 human leukocyte antigen–matched donors. Patients were randomized (1:1) to the Iomab-B arm or conventional care (CC) arm. In the Iomab-B arm, patients received an outpatient dose of Iomab-B followed by nuclear medicine imaging to determine via dosimetry the patient-specific therapeutic dose. Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) was performed 12 to 14 days following the infusion of a therapeutic dose of Iomab-B, and a nonmyeloablative conditioning backbone of fludarabine (30 mg/m2 x 3) and low-dose total body irradiation (2 Gy x 1 dose). Patients on the CC arm received salvage therapy, including newly approved targeted agents, at the discretion of the investigator. If patients achieved complete response (CR), they could proceed to conditioning (exact regimen being physician’s choice) and allo-HSCT. Patients not achieving CR in the CC arm could cross over and receive Iomab-B–based conditioning and allo-HSCT.
Interim data were available for 113 patients. A total of 56 patients (median age, 63 years) were randomized to Iomab-B and received allo-HSCT. Despite a pretherapy median of 30% marrow blasts, all Iomab-B patients engrafted. In the CC arm, 48 of 57 (84%) patients failed salvage therapy. Thirty of these patients (median, 22% marrow blasts) crossed over and received Iomab-B and allo-HSCT. Patient age, donor type (matched related donor or matched unrelated donor), bone marrow cellularity, blast percentage, stem-cell dose, administered Iomab-B activity (in millicuries [mCi]), and absorbed radiation dose to the marrow (Gy) were analyzed for time to engraftment among each group. High rates of allo-HSCT with curative potential were observed in 88% of patients in the Iomab-B arm and 79% of patients who crossed over. Neither the radiation dose delivered to the marrow (median, 14.8 Gy; range, 4.6-32 Gy) nor the total administered activity (median, 641 mCi; range, 354-1027 mCi) demonstrated significant correlation with time to neutrophil engraftment or platelet engraftment.
In conclusion, despite a heavy leukemia burden, with median bone marrow blasts of 30% prior to allo-HSCT (Iomab-B arm), delivering Iomab-B via a personalized dosimetric approach resulted in absorbed marrow radiation doses that facilitated consistent engraftment following allo-HSCT among older patients with R/R AML. In addition, no relationship was found between speed of engraftment and total administered activity (in mCi) or radiation dose (in Gy) delivered to the bone marrow.
Reference
Gyurkocza B, Nath R, Choe H, et al. Personalized Targeted Radioimmunotherapy with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] in Patients with Active Relapsed or Refractory Acute Myeloid Leukemia Results in Successful Donor Hematopoietic Cells Engraftment with the Timing of Engraftment Not Related to the Radiation Dose Delivered. Presented at: 62nd American Society of Hematology Annual Meeting & Exposition, December 5-8, 2020. Abstract 193.