Iomab-B may increase transplant access, improve outcomes in relapsed/refractory AML
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Targeted conditioning with iodine (131I) apamistamab enabled older patients with relapsed or refractory acute myeloid leukemia to undergo allogeneic hematopoietic stem cell transplantation, according to results of the phase 3 SIERRA trial.
The findings, presented at 2023 Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, showed iodine (131I) apamistamab, known as Iomab-B (Actinium Pharmaceuticals), led to rapid engraftment and durable complete remissions vs. conventional care, with low incidence of serious adverse events among a patient population typically ineligible for HSCT.
Background
Many patients with active relapsed or refractory AML, especially those who are older, are not offered HSCT because of failure to achieve remission, poor tolerance of conditioning and substantial transplant-related mortality, Sergio A. Giralt, MD, FACP, FASTCT, deputy division head of the division of hematologic malignancies and Melvin Berlin family chair in multiple myeloma at Memorial Sloan Kettering Cancer Center, professor of medicine at Weill Cornell Medical College, and HemOnc Today Editorial Board Member, said during a presentation.
Iodine (131I) apamistamab consists of an anti-CD45 antibody conjugated to radioactive iodine. Developed at Fred Hutchinson Cancer Research Center, the agent is designed to deliver high-dose targeted radiation to hematopoietic stem cells along with reduced-intensity conditioning before allogeneic HSCT.
Methodology
The prospective, randomized SIERRA trial compared rates of durable complete remission at 6 months after initial complete remission with Iomab-B vs. physician’s choice of conventional care prior to HSCT. Giralt presented efficacy and safety results among 153 patients aged 55 years or older with active relapsed or refractory AML and considered candidates for reduced-intensity conditioning. Patients in the Iomab-B group (n = 76; median age, 64 years) received a dosimetric dose of 20 millicuries and then a personalized single dose of the agent followed by a reduced-intensity conditioning regimen of fludarabine and total body irradiation.
The per-protocol analysis set included 59 patients in the Iomab-B group and 64 of 77 patients (median age, 66 years) in the conventional care group, of whom 44 had crossed over to the Iomab-B group.
Giralt noted the 30% median percentage of marrow blasts at randomization in the Iomab-B group. “Just think, how many patients would you actually transplant with 30% blasts in the bone marrow?” he said.
The Iomab-B group had a shorter time to HSCT from randomization than the conventional care group (median, 29 days vs. 66.5 days), but the groups had similar median time to engraftment and HSCT comorbidity index.
Results
Among evaluable patients in the per-protocol group 44 (74.6%) in the Iomab-B group achieved complete remission with or without platelet recovery 30 days after induction, compared with four (6.3%) in the conventional care group. Moreover, 13 patients (22%) assigned Iomab-B remained in complete remission at 180 days or longer vs. none in the conventional care group (P < .0001).
Most patients (91%) in the crossover group underwent transplant. More than half of them (52.3%) achieved complete remission with or without platelet recovery, and six (13.6%; 95% CI, 5.17-27.35) had durable complete remissions of 180 days or longer.
In total, 60% of those who achieved durable complete remission after receipt of Iomab-B reached the 2-year survival mark, Giralt said.
A comparison of the treatment groups excluding crossover showed the Iomab-B group had longer median OS (6.4 months vs. 3.2 months) and a higher 1-year OS rate (26% vs. 13.1%), as well as longer median duration of follow-up (6.3 months vs. 3 months). The crossover group had median OS of 7.1 months, a 1-year OS rate of 35.8% and median duration of follow-up of 7.1 months.
“The benefit of Iomab-B was seen across all different subgroups, particularly in patients with performance status of less than 90 and patients with adverse cytogenetics,” Giralt said.
The Iomab-B group also had a higher rate of 6-month EFS than the conventional care group (28% vs. 0.2%; P < .0001).
The conventional care group had higher rates of treatment-emergent adverse events including sepsis (28.6% vs. 6.1%), febrile neutropenia (50% vs. 43.9%) mucositis (21.4% vs. 15.2%) and grade 3 to grade 4 acute graft-versus-host disease (14.3% vs. 9.4%).
Implications, next steps
Actinium Pharmaceuticals plans to file a biologics license application seeking FDA approval of Iomab-B for adults aged 55 or older with relapsed or refractory AML who cannot proceed to bone marrow transplant with available therapies, the company stated in a press release.
“Iomab-B offers a novel solution to increase access to transplant and improve outcomes in patients with relapsed/refractory AML,” Giralt said. “This is a potential new standard of care for patients failing to achieve a remission. Further exploration of Iomab-B in other indications and with different conditioning regimens and donor types is warranted and planned.”
References:
- Gyurkocza B, et al. Abstract LBA3. Presented at: Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, Feb. 15-19, 2023; Orlando.
- Actinium announces positive full data results from the pivotal phase 3 SIERRA trial in patients with active, relapsed or refractory acute myeloid leukemia (press release). Available at: ir.actiniumpharma.com/press-releases/detail/437/actinium-announces-positive-full-data-results-from-the. Published Feb. 18, 2023. Accessed Feb. 20, 2023.
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Gyurkocza B, et al. Abstract LBA3. Presented at: Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, Feb. 15-19, 2023; Orlando.
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