TY - JOUR T1 - Low Incidence Rates of Mucositis, Febrile Neutropenia or Sepsis in the Prospective, Randomized Phase 3 Sierra Trial for Patients with Relapsed or Refractory Acute Myeloid Leukemia with Targeted Delivery of Anti-CD45 Iodine (<sup>131</sup>I) Apamistamab [Iomab-B] JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1694 LP - 1694 VL - 62 IS - supplement 1 AU - Mona Natwa AU - Susan Passalaqua AU - Ming-Kai Chen AU - Robert Wagner AU - Wendell Yap AU - Landis Griffeth AU - Gregory Wiseman AU - Joyce Mhlanga AU - Richard Wahl AU - Norbert Avril AU - Robert Hellman AU - Dominick Lamonica AU - Manuela Matesan AU - Beth Chasen AU - Neil Hansen AU - Eugene Leung AU - Joseph Osborne AU - Jennifer Peterson AU - Yusuf Menda AU - Dinko Franceschi AU - Qing Liang AU - Vijay Reddy AU - Mark Berger AU - Neeta Pandit-Taskar Y1 - 2021/05/01 UR - http://jnm.snmjournals.org/content/62/supplement_1/1694.abstract N2 - 1694Background: Despite recently approved novel targeted therapies, most patients with high-risk acute myeloid leukemia (AML) still require allogeneic hematopoietic stem cell transplantation (HSCT) to achieve long-term survival. However, older patients with relapsed/refractory (R/R) AML are often unable to undergo HSCT due to the toxicity of myeloablative pre-conditioning. Since higher doses of chemotherapy or radiation are associated with prolonged myelosuppression or infectious complications, targeted radioimmunotherapy with Iomab-B (131I labeled apamistamab antibody), employed in the SIERRA trial, was designed to reduce toxicities in a patient population unable to tolerate standard high-dose myeloablative HSCT pre-conditioning. Iomab-B targets CD45, which is highly expressed on leukemia cells. We hypothesize that Iomab-B, which spares non-hematologic organs such as the GI tract, exhibits a favorable toxicity profile with respect to mucositis, febrile neutropenia (FN), and sepsis. Methods: SIERRA trial is a prospective trial for patients ≥ 55 years of age with R/R AML. Patients were randomized (1:1) to Iomab-B or Conventional Care (CC). Those in the Iomab-B group received a dosimetric infusion of Iomab-B followed by personalized therapeutic dose based on gamma camera imaging. Therapeutic dose calculations, utilizing the Olinda software (V2.1, Hermes Medical) to determine the delivery of a maximum of 24 Gy liver dose, were performed. HSCT was performed 12-14 days following the infusion of a therapeutic dose of Iomab-B and a non-myeloablative conditioning backbone of fludarabine (30 mg/m2 x 3) and 2 Gy of total body irradiation. Common non-hematologic Grade 3 or 4 adverse events (AEs) were evaluated from time of randomization and up to 100 days after HSCT in all patients who received Iomab-B. Statistical analysis was performed with activity of Iomab-B, as well as with the dose delivered to other organs, including GI tract, and the incidence of 3 AEs (FN, Mucositis and sepsis). For each of the 3 AEs of interest, a multivariate analysis was performed, allowing each of the predictor variables to be included in the model. Results: A total of 113 patients were randomized at the time of analysis. For those randomized to Iomab-B, data are available for 49 patients that received a therapeutic dose of Iomab-B and HSCT. The median dose of Iomab-B administered was 646 mCi (range 354-1027 mCi) and the median radiation dose delivered to the marrow in the Iomab-B group was 14.7 Gy (range 4.6-32 Gy). All patients (median age 64) treated with a therapeutic dose of Iomab-B achieved neutrophil engraftment, despite the high marrow blasts prior to initiation of therapy. Rates of AEs are shown in Table 1 and the organ doses are listed in Table 2. No correlation between FN, mucositis, sepsis and administered Iomab-B activity (p = 0.08), nor with dose delivered to GI tract (p = 0.09), was observed. Iomab-B showed a lower incidence of sepsis (p = 0.026), and trends towards reduced rates of severe mucositis, FN, when compared to CC arm (Table 3). Conclusions: Targeted myeloablative conditioning with Iomab-B resulted in low incidences of severe mucositis, FN, and sepsis. Unlike treatment with cytotoxic chemotherapy and total body irradiation, where mucositis, neutropenic infections, and sepsis increase with the administered dose, these were not correlated to the dose of Iomab-B administered or to the specific radiation dose delivered to the marrow or critical organs. Furthermore, the GI tract received a low dose of radiation (median of 2.8 Gy) compared to the larger dose (median of 14.7 Gy) delivered to the marrow. These results represent potentially significant improvements in the safe delivery of myeloablative therapy with high-dose targeted radioimmunotherapy prior to HSCT in older patients with R/R AML. ER -