In findings from the phase 3 SIERRA trial, Iomab-B-based conditioning for patients with relapsed or refractory acute myeloid leukemia provided significant efficacy and tolerable safety results over the current standard of care.
The use of Iomab-B-based conditioning with allogeneic hematopoietic cell transplantation (alloHCT) showed rapid engraftment and high initial complete remission with/without platelet recovery (CR/CRp) and showed a significant improvement for patients that achieved a durable complete remission (dCR) when compared with conventional care for patients with relapsed/refractory (R/R) acute myeloid leukemia (AML).1
These updated findings from the pivotal, randomized phase 3 SIERRA trial (NCT02665065) were presented at the 2023 Tandem Meetings on Transplantation and Cellular Therapy that demonstrated the effectiveness of targeted radiotherapy over conventional care for older patients with R/R AML. This study met its prespecified primary end point with 22% (n = 13) of patients on Iomab-B maintaining a dCR for 180 days or more compared with none in the control arm (95% CI, 12.29%-34.73%; P < .0001).
In the Iomab-B arm, of the 59 evaluable patients 74.6% (n = 44) achieved a CR/CRp compared with 6.3% (n = 6.3) of 64 evaluable patients in the control arm. In the arm of 44 patients who crossed over from the control arm to receive Iomab-B, 91% received transplant and 52.3% of these patients achieved a CR/CRp. Moreover, 6 of the crossover patients had a dCR of 180 days or more at the time of follow up (95% CI, 5.17%-27.35%).
According to Sergio Giralt, MD, deputy head, Division of Hematologic Malignancies at Memorial Sloan Kettering Cancer Center, who presented the data in place of Boglarka Gyukocza, MD, at the meeting, patients on conventional chemotherapy were given post-HCT maintenance therapy based on the physician’s choice compared to patients on the Iomab-B arm only receiving FLT3 inhibitors for patients with a FLT3 mutation.
Giralt highlighted that the promising response rates translated to a doubling of overall survival (OS) among the 76 patients in the Iomab-B arm at a median of 6.4 months (95% CI, 5.1-7.9) compared with 3.2 months (95% CI, 1.6-7.0) in the 33 patients given conventional chemotherapy, excluding those on the crossover arm. Twenty-six percent (95% CI, 16.7%-36.4%) of patients on Iomab-B were alive at 1 year compared with 13.1% (95% CI, 4.2%-27.4%) of patients on the conventional chemotherapy arm. Patients in the crossover arm demonstrated a median OS of 7.1 months (95% CI, 5.2-9.2), and 1-year OS of 35.8% (95% CI, 22.0%-49.8%).
The median duration of response was also doubled in the Iomab-B arm at 6.3 months (95% CI, 0.5-49.5) vs 3 months (95% CI, 0.6-28.8) in the conventional arm; however, it was longest in the crossover arm at 7.1 months (95% CI, 1.7-56.5).
Long-term OS was also observed among 13 patients with a dCR, with all patients surviving at 6 months, 92.3% at 12 months, 71.9% at 18 months, and 59.9% at 24 months. Event-free survival (EFS) was also significantly improved in the Iomab-B arm with 28% of patients experiencing EFS at 180 days compared with 0.2% in the conventional chemotherapy arm (HR, 0.22; 95% CI, 0.15-0.34, P < .0001).
According to Giralt, OS with Iomab-B was favored among all subgroups in the trial; however, he highlighted 2 subgroups of patients with significant improvements: those with a Karnofsky Performance Status (KPS) score less than 90 (n = 45; HR, 0.44; 95% CI, 0.25-0.77) and those with adverse or poor cytogenetic risk (n = 43; HR, 0.43; 95% CI, 0.25-0.75).
At the time of randomization, most patients in both arms had a primary induction failure (56.6% vs 51.9%, respectively), a median of 3 prior lines of treatment, and 47 patients in each arm had received prior targeted therapy.
“The median age [of patients on Iomab-B] was 64 years old, which is important because this is different from the ASAP trial [NCT02461537], which I know many [clinicians are] thinking about,” explained Giralt. “Many of these patients were either relapsed/refractory or who were beyond second relapse, and only half of the patients were primary induction failures.”
Iomab-B is used to prepare and condition patients for hematopoietic stem cell transplantation instead of chemotherapy, which is the current standard of care for this patient population.
The SIERRA study looked at 153 patients aged 55 years or older diagnosed with R/R AML, who were administered either Iomab-B or conventional therapy, both prior to alloHCT. Patients in the control arm could receive chemotherapy with either cytarabine and daunorubicin, or targeted therapy with a Bcl-2 inhibitor, FLT3 inhibitor, or IDH 1/2 inhibitor.
Patients were randomized 1:1 to either Iomab-B then HCT or conventional care. Patients 55 years or older with active disease and a BM blast count of 5% or had the presence of circulating blasts were eligible for the trial. Eligible patients also could have a KPS score of 70 or more, an 8/8 allele-level, or a related or unrelated matched donor; however, patients with previous HCT were excluded.
Observing for efficacy results, researchers also looked at tolerability of Iomab-B finding it to be tolerable among 66 evaluable patients compared to 14 on the conventional arm. The most common adverse events in the Iomab-B arm vs conventional chemotherapy arm included febrile neutropenia (43.9% vs 50%, respectively), mucositis (15.2% vs 21.4%), and sepsis (6.1% vs 28.6%). The cumulative incidence of grades III-IV acute graft-vs-host-disease was lower in the Iomab-B arm at 9.4% (95% CI, 3.8%-18.2%) compared with 14.3% (95% CI, 2.1%-37.6%) in the conventional care arm.
“A significant proportion of patients who achieve a durable complete remission are long-term survivors,” concluded Giralt. “Iomab-B offers a novel solution to increase access to transplant and improve outcomes in patients with relapsed/refractory AML and is a potential new standard of care for patients failing to achieve a remission.”
Based on results from the SIERRA study, Actinium Pharmaceuticals, Inc, the manufacturer behind Iomab-B, plans to submit a biologics license application to the FDA for the approval of the therapy in patients aged 55 years old or older who cannot access bone marrow transplant with the current standard of care.2