Iomab-B Radiotherapy Enables Transplantation in Acute Myeloid Leukemia

The targeted radiotherapy Iomab-B enabled a cohort of patients with transplant-ineligible relapsed/refractory acute myeloid leukemia (AML) to receive bone marrow transplants, which yielded higher rates of response and survival, according to data from the phase 3 SIERRA trial (NCT02665065), according to a press release from Actinium Pharmaceuticals.

Investigators plan to submit a biologics license application for Iomab-B to the FDA based on findings from the phase 3 SIERRA trial.

These data were presented recently at the European Society for Blood and Marrow Transplantation (EBMT) 49th Annual Meeting. Additional results were previously presented at the 2023 Tandem Meetings. All patients who received Iomab-B treatment became eligible for transplant and engraftment, compared with 17% of patients in the control arm. For those eligible, time to transplant was 29.0 days in the Iomab-B arm vs 66.5 days in the control arm. The rates of complete remission at 30 days were 75% and 6.3%, respectively, in the experimental and control arms.

In the Iomab-B arm, the rates of durable complete remission (dCR) were 22% and 0% in the control arm (P <.0001). Event-free survival (EFS) was 26% vs 0.2% (hazard ratio [HR], 0.22; P <.0001), between both arms, respectively.

Patients who experienced a dCR after treatment with Iomab-B had a survival rate of 92% at 1 year and 60% at 2 years; median overall survival (OS) has not yet been reached in this population. In the overall population, median OS was 6.4 months among those treated with Iomab-B vs 3.2 months in the control arm among patients who did not cross over; the corresponding survival rates at 1 year were 26.1% and 13.1%

“Despite 10 drug approvals for AML since 2017, approximately 30% of patients never achieve a remission and over 50% develop relapsed or refractory disease, which is associated with dismal survival outcomes of 2 to 4 months,” Avinash Desai, MD, chief medical officer at Actinium, said in the press release. “Bone marrow transplant remains the only potentially curative treatment option for patients with relapsed/refractory AML, but current clinical practice precludes the overwhelming majority of [these] patients from [transplant] due to the need to first achieve remission and the use of highly toxic, non-targeted chemotherapies for conditioning.”

Iomab-B is a targeted radiotherapy designed to improve bone marrow transplant by depleting blood cancer, immune, and bone marrow stem cells that uniquely express CD45. The phase 3 SIERRA trial is a randomized, multicenter study assessing Iomab-B vs physician’s-choice salvage therapy across 153 patients.

The median age in the study population was 64 years old (range, 55-77). Patients had a median blast count of 30% and had undergone a median of 3 prior lines of treatment (range, 1-8). More than 90% of patients had intermediate or adverse cytogenetics and molecular risk, and 78% had experienced primary induction failure or first early relapse.

Treatment with Iomab-B also produced fewer toxicities; sepsis occurred in 6.1% of patients in the experimental arm vs 28.6% in the control arm. The rates of febrile neutropenia, mucositis, and acute graft-versus-host-disease were also lower in the experimental arm than the control arm.

Actinium announced its intention to submit a biologics license application for Iomab-B to the FDA in 2023 based on data from the SIERRA trial.

“If approved, Iomab-B can be practice changing by enabling patients with relapsed/refractory AML with active disease, one of the largest segments of AML, to access [bone marrow transplantation] in days, via a single therapeutic infusion, without having to first achieve a remission,” Desai concluded.

Reference

Actinium announces positive pivotal phase 3 SIERRA trial results of Iomab-B showcased to the European Transplant Community in oral presentation at the European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting. News Release. Actinium Pharmaceuticals, Inc. April 27, 2023. Accessed April 28, 2023. https://bit.ly/3ndnRks