Iomab-B Leads to High Bone Marrow Transplant Rate in Relapsed/Refractory AML

Sergio A. Giralt, MD

Treatment with iodine-131 apamistamab (Iomab-B) led to a high bone marrow transplant rate compared with salvage chemotherapy in elderly patients with relapsed/refractory acute myeloid leukemia (AML), according to interim findings of the first 75 patients enrolled on the phase III SIERRA trial (NCT02665065).¹

All patients receiving a therapeutic dose of Iomab-B (n = 31) received a bone marrow transplant and were rapidly engrafted without experiencing delays in blood count recovery, compared with an initial complete response (CR) of 18% in the control arm who could proceed to conventional bone marrow transplant.

"The results from the first 50% of patients to be enrolled in the SIERRA trial continue to be highly encouraging, particularly Iomab-B's ability to enable a transplant in this patient population that would otherwise be ineligible,” Sergio Giralt, MD, chief of Adult BMT, Memorial Sloan Kettering Cancer Center, and chair of Myeloma Service, stated in a press release. “Despite eight new therapies having been approved for patients with AML, better outcomes for patients with AML are needed, in particular for the large number of relapsed and refractory patients. Newly approved targeted agents are not curative and as seen in the SIERRA trial do not enable a high rate of potentially curative BMT."

CD45 is expressed by a variety of hematopoietic cells, including leukemia, lymphoma, and all immune cells. Prior data have shown that delivery of high doses of Iomab-B, which targets CD45, depletes hematopoietic stem cells. Targeted radiation to leukemia cells also elicits a direct antitumor effect.

In the 150-patient, phase III SIERRA trial, investigators are randomizing patients ≥55 years with active, relapsed/refractory AML 1:1 to receive Iomab-B compared with salvage chemotherapy. Patients who achieve a CR to chemotherapy can continue treatment with a standard regimen or proceed to hematopoietic stem cell transplant (HSCT). Those who do not achieve a CR can cross over to receive Iomab-B; the dose of this treatment is individualized to achieve radiation exposure to the liver ≤24 Gy.

The median age is 64 years (range, 55-76) and all patients have active disease with a median bone marrow blast percentage of 28% (range, 5%-98%) at randomization. Patients were either of intermediate or poor risk groups; 68% of patients enrolled were in poor prognostic adverse cytogenetic and molecular risk group.

Thirty-two percent of patients who were randomized to the control arm received available targeted agents; 92% of these patients received venetoclax (Venclexta) with either a hypomethylating agent or low dose cytarabine. Of these, 27% of patients achieved a CR.

The primary endpoint of the study is durable CR rate, defined as a morphologic CR lasting for at least 180 days; the secondary endpoint was overall survival (OS) at 1 year.

Results also showed that the 100-day non-relapse transplant-related mortality remains lower in the Iomab-B arm (3%) versus 29% for patients in the control arm who received conventional transplants. Of the 31 patients who received Iomab-B in the study arm, 30 are potentially evaluable for the primary endpoint compared with 5 in the control arm, which remains consistent with interim data reported at 25% of enrollment.

The number of days to achieve absolute neutrophil count engraftment was 15 in the Iomab-B arm, 18 for those who had a CR after salvage therapy, and 13 for those who had no CR after salvage therapy; the number of days to platelet engraftment was 18, 22, and 17 days, respectively. The number of days to HSCT from day of randomization was 30 in the Iomab-B arm, 67 in those who achieved CR after salvage chemotherapy, and 64 days in those who did not achieve CR after chemotherapy.

"We are thrilled that data from the halfway point of the SIERRA trial validate the promising interim safety and feasibility results from the first 25% of patients in this trial,” Mark Berger, MD, chief medical officer, Actinium Pharmaceuticals, stated in the press release. “It is particularly gratifying for me to see that these relapsed, refractory patients with heavy disease burden who received a therapeutic dose of Iomab-B were successfully transplanted.

“In addition, it is heartening that Iomab-B can be an effective pathway to transplant even when the recently approved targeted therapies unfortunately fail, as shown by our control arm and crossover data. With the first half of the trial behind us and with strong data in hand, we are focused on taking this message to hematologists and transplant physicians. We look forward to continuing to execute on our strategies to bring Iomab-B to patients as quickly as possible."

Earlier data from the study were presented in February 2019.² Data showed that all but 1 of the first 19 patients randomized to Iomab-B had a CR and successful engraftment; the 1 patient who did not have successful engraftment did not receive a therapeutic dose of Iomab-B. Nine out of 10 patients who crossed over from conventional treatment had successful engraftment.

References

1. Actinium Announces Positive Interim Results from Iomab-B Pivotal Phase 3 SIERRA Trial at 50% of Total Patient Enrollment. Actinum Pharmaceuticals, Inc. Published October 28, 2019. https://yhoo.it/32Tg77H. Accessed October 28, 2019.
2. Agura E, Gyurkocza B, Nath R, et al. Novel re-induction and anti-CD45 targeted conditioning with iodine (131I) apamistamab [Iomab-B] yields encouraging results in older patients with active, relapsed or refractory AML (R/R AML): safety & feasibility data from the prospective randomized phase III SIERRA trial. Presented at: 2019 Transplantation & Cellular Therapy Meetings; February 20-24, 2019; Houston, TX. Abstract LBA3.