The SIERRA trial is a prospective, randomized phase 3 trial in older patients with relapsed/refractory acute myeloid leukemia (R/R AML). The hypothesis of this study is that a targeted delivery of radiation to the bone marrow would facilitate successful engraftment despite active disease in the marrow. The delivery of radiation to the bone marrow was achieved through an infusion of a therapeutic dose of iodine-131-apamistamab (Iomab-B) to the liver with a limit of 24 Gy radiation.
Patients included in this study were required to be aged ≥55 years with active R/R AML (≥5% blasts), have sufficient organ function, and have related/unrelated 8/8 human leukocyte antigen–matched donors. Patients were randomized to either the Iomab-B arm or conventional care (CC) arm in a 1-to-1 manner. Patients in the Iomab-B arm received a patient-specific therapeutic dose of Iomab-B as determined via dosimetry using nuclear medicine imaging. In addition to lomab-B, patients received a nonmyeloablative conditioning backbone of fludarabine (30 mg/m2 x 3) and low-dose total body irradiation (2 Gy x 1 dose). Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) was performed 12 to 14 days thereafter. At the discretion of the investigator, patients in the CC arm received salvage therapy, which could include newly approved targeted agents. Patients achieving a complete response (CR) could proceed to physician’s choice of conditioning and allo-HSCT. Patients could cross over to the lomab-B arm if they did not achieve CR.
At cutoff, data were available for 113 patients with a median age of 63 years. Of these, 56 patients were randomized to the Iomab-B arm and received allo-HSCT. All patients in the lomab-B arm engrafted despite a pretherapy median of 30% marrow blasts. A total of 57 patients were randomized to the CC arm, of which, 48 (84%) failed salvage therapy. Thirty of these patients, with a median of 22% marrow blasts, crossed over to the Iomab-B arm and received allo-HSCT. High rates of allo-HSCT with curative potential were observed in 88% of patients in the Iomab-B arm and 79% of crossover patients. No significant correlation was found between time to neutrophil engraftment or platelet engraftment and the radiation dose delivered to the marrow (median, 14.8 Gy; range, 4.6-32 Gy) or the total administered activity (median, 641 mCi; 354-1027 mCi).
In summary, delivering Iomab-B to the liver resulted in absorbed marrow radiation doses that facilitated consistent engraftment following allo-HSCT among older patients with R/R AML despite a heavy leukemia burden. In addition, no correlation was shown between total administered activity or radiation dose delivered to the bone marrow and speed of engraftment.
Reference
Abstract 193. ASH 2020. December 5, 2020. 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.