AML-123: Targeted Conditioning with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] Leads to High Rates of Transplantation and Engraftment in Older Patients with Active, Relapsed, or Refractory (rel/ref) AML: Preliminary Midpoint Results from the Prospective, Randomized Phase 3 SIERRA Trial

Context Despite new therapies for AML, older patients with rel/ref AML do not have durable responses and are ineligible for potentially curative HCT. The SIERRA trial addresses this unmet need. Objective Midpoint analysis, with safety, engraftment data, and transplant rates. Design Phase 3, randomized patients in the CC arm who do not attain remission may then receive Iomab-B followed by HCT. Setting USA and Canada. Patients or other participants Aged ≥55 years with active rel/ref AML. Interventions Iomab-B plus RIC (FLU/TBI) and HCT, or CC. Main outcome measures Primary endpoint - durable CR (dCR) ≥ 180 days. However, this analysis is on safety and transplant rates. Results First 50% of patients (n=75) had a median age of 64, with 85% failing ≥2 induction therapies and 33% failing targeted therapies. Median baseline marrow blasts Iomab-B (30%) and CC (26%). All patients transplanted after Iomab-B engrafted (median days 15 for ANC, 18 for platelets). After randomization, 82% (31/38) patients in the CC arm failed salvage therapy, despite 32% (12/38) receiving targeted therapy. Majority (73%, 8/11) of patients receiving venetoclax with HMA or LDAC did not achieve remission. Of the 31 patients not achieving remission on CC, 20 (65%) crossed over to receive Iomab-B/HCT. The most common reason preventing crossover was disease progression. CC showed increased incidence of Grade ≥3 febrile neutropenia vs Iomab-B (46% vs 23%). Iomab-B administration was generally well tolerated with 1 Grade 3 and no Grade 4 infusion reactions. There were no Iomab-B-related deaths and 100-day non-relapse mortality was 6% on the Iomab-B arm. Conclusions Despite advanced age, active disease and many prior therapies, 84% (31/37) of all patients in the Iomab-B arm were able to undergo HCT and all successfully engrafted. In comparison, only 18% (7/38) of the patients on the CC arm achieved remission and underwent conventional HCT despite a high percentage receiving recently approved agents and targeted therapies. Iomab-B has a favorable safety profile with no graft failures and low transplant-related mortality. These preliminary results represent significant improvements over the current rates of transplantation in this patient population. SIERRA trial is currently enrolling ( www.sierratrial.com or clinicaltrials.gov NCT02665065 ).