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

Hannah Choe, Dr. Rajneesh Nath, Dr. Stuart E. Seropian, Mark R. Litzow, Camille Abboud, Nebu Koshy, Patrick J. Stiff, Benjamin Tomlinson, Sunil H. Abhyankar, James Foran, …
Transplantation and cellular therapy, Vol.30(2 Supplement), pp.S59-S60
02/2024
DOI: 10.1016/j.jtct.2023.12.094

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Abstract

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. 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). 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. 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.

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