Iomab-B Leads to More Durable Responses vs alloHCT in AML Treatment

Microscopic image of bone marrow cells - Generated with Google Gemini AI

Treatment with Iomab-B (¹³¹I-apamistamab), a CD45-targeted radiotherapy, was linked to higher durable complete remission (dCR) rates compared with conventional care among older patients with relapsed/refractory acute myeloid leukemia (AML), according to findings from the phase 3 SIERRA study (NCT02665065).¹

In the intent-to-treat population, the dCR rate was 17.1% (95% CI, 9.4%-27.5%) with Iomab-B vs 0% (95% CI, 0%-4.7%) with conventional care of salvage therapy followed by allogeneic hematopoietic cell transplant (alloHCT). This met the study’s primary end point. HR for overall survival (OS) was 0.99 (95% CI, 0.70-1.41; P =.96) and HR for event-free survival was 0.23 (95% CI, 0.15-0.34).

Grade 3 or higher treatment-related adverse effects were comparable between the 2 arms, with 59.7% and 59.2% of the Iomab-B and conventional care arms experiencing them, respectively.

"The SIERRA trial was important for the field of transplant and demonstrated for the first time in a randomized study that the CD45 antibody-radioconjugate Iomab-B can provide patients with improved access to a potentially curative hematopoietic stem cell transplant, and improved outcomes compared [with] current chemotherapy-based regimens. Importantly, Iomab-B demonstrated a statistically significant improvement in key efficacy end points including durable complete remission and event-free survival,” said Sergio Giralt, MD, deputy division head, Division of Hematological Malignancies, and attending physician, Adult Bone Marrow Transplant Service at Memorial Sloan Kettering Cancer Center, and SIERRA trial investigator, in a press release.²

“Despite multiple drug approvals for patients with AML, there remains no curative options for older patients with relapsed or refractory disease and outcomes for these patients also remain dismal. My fellow investigators and I are disappointed that the SIERRA trial will not support the approval of Iomab-B despite the positive results and significant unmet medical need of this patient population. However, there is continued significant interest from the transplant community to participate in the upcoming phase 3 study with Iomab-B to provide patients access to this important drug candidate,” Giralt added.

In August 2024, the FDA stated that data from the SIERRA trial would not be sufficient to support a biologics license application and required another randomized study for filing. The FDA recommended that Actinium Pharmaceuticals, the sponsor, conduct a study evaluating alloHCT using Iomab-B plus a reduced-intensity condition regimen of fludarabine and total-body irradiation vs alloHCT and reduced-intensity conditioning with cyclophosphamide, fludarabine, and total-body irradiation.³

Additionally, the new study should not allow crossover. In the SIERRA trial, 44 of 77 patients crossed over from the conventional care arm to the Iomab-B arm,¹ potentially confounding OS results.

REFERENCES:

1. Gyurkocza B, Nath R, Seropian S, et al. Randomized phase III SIERRA trial of 131I-Apamistamab before allogeneic hematopoietic cell transplantation versus conventional care for relapsed/refractory AML. J Clin Oncol. Published online September 19, 2024. doi:10.1200/JCO.23.02018

2. Actinium Pharmaceuticals announces publication of results from the phase 3 SIERRA Trial of Iomab-B in the Journal of Clinical Oncology. News release. Actinium Pharmaceuticals, Inc. September 20, 2024. Accessed September 23, 2024. https://tinyurl.com/69kb9e3b

3. Actinium provides regulatory update on planned BLA filing and future plans for Iomab-B in the US. News release. Actinium Pharmaceuticals, Inc. August 5, 2024. Accessed September 23, 2024. https://tinyurl.com/44htcubs