Targeted Myeloablative Radiation Using 131I-Apamistamab Prior to Allogeneic Hematopoietic Cell Transplant for Patients with R/R AML Results in Robust Engraftment

Background Most older patients (pts) with relapsed or refractory (r/r) AML cannot tolerate intensive treatment and are not eligible for curative allogeneic hematopoietic cell transplant (HCT). Iomab-B (131I-apamistamab), an anti-CD45 radioimmunoconjugate, safely delivers targeted radiation to hematopoietic cells, allowing for myeloablation and eradication of leukemic cells. Iomab-B based induction and conditioning can provide these pts with access to HCT. Methods SIERRA (NCT02665065) was a multi-center, randomized, controlled phase 3 study comparing the efficacy of Iomab-B based conditioning vs physician's choice of Conventional Care (CC) in pts ≥55 years of age with active, r/r AML. Pts were randomized (1:1, N=153) to CC or Iomab-B with fludarabine and total body irradiation (2 Gy) followed by HCT. Primary endpoint was durable CR (dCR), defined as CR/CRp ≥6 mos. CR/CRp assessment was 28-56 days post HCT on the Iomab-B arm or 28-42 days post start of CC. Pts not achieving CR/CRp could crossover (CO) to Iomab-B. We analyzed time to neutrophil and platelet engraftment, and complete donor chimerism (defined as >95% donor cells detected in bone marrow or blood) rates in each transplanted group (Iomab-B, CO and CC). Results A total of 153 pts were enrolled in the SIERRA trial, 76 in the Iomab-B arm and 77 in the CC arm. Baseline characteristics were well balanced between both arms (Table 1). The primary endpoint of dCR at 6 mos strongly favored Iomab-B with 22% dCR vs. 0% for CC (p<0.0001). Of the 106 pts who received a therapeutic dose (TD) of Iomab-B (Iomab-B=66, CO=40), 100% underwent HCT vs. 14 (18.2%) on the CC arm. The median radiation dose to marrow was 16 Gy (range: 4.6-44.6 Gy), 100% engraftment was achieved without any graft rejection. Median times to neutrophil and platelet engraftment were 14 days (range 9-31) and 19 days (range 10-40) for Iomab-B arm; 13 days (range 10-35) and 18.5 days (range 12-38) for CO pts; 16 days (range 13-83) and 15 days (range 8-35) for the CC+HCT arm respectively (Table 2). Ninety of the 106 pts that received Iomab-B+HCT were evaluable for chimerism by day +90 with 79% (71/90) having complete donor chimerism and 21% mixed chimerism which was due to persistent AML. Cumulative incidence of grade III-IV acute graft-versus-host-disease (GvHD) for pts receiving Iomab-B was 9.4% vs. 14.3% for those on CC+HCT arm. The cumulative incidence of chronic GvHD at 12 mos was 16.9% and 13.5% for Iomab-B and CO pts respectively; no pts on the CC+HCT arm were evaluable for chronic GvHD at one year due to death or relapse. Conclusion Despite receiving a very high dose of targeted radiation to the marrow, having a high leukemia burden and being heavily pre-treated, all pts undergoing HCT using the Iomab-B led regimen achieved engraftment that was robust and comparable to those in the CC arm who received standard of care conditioning. Iomab-B pts had overall low rates of chronic and acute grade III-IV GvHD.