As reported in Journal of Clinical Oncology by Gyurkocza et al, the phase III SIERRA trial has shown higher rates of durable complete remissions with the anti-CD45 radioconjugate iodine-131–apamistamab vs conventional care followed by allogeneic hematopoietic cell transplantation (allo-HCT) in patients aged ≥ 55 years with relapsed or refractory acute myeloid leukemia.
Study Details
In the open-label trial, 153 patients from 22 sites in North America were randomly assigned between February 2017 and October 2021 to receive an I-131–apamistamab–led regimen (n = 76) or conventional care (n = 77). Patients in the I-131–apamistamab group received a single therapeutic I-131–apamistamab infusion, followed by fludarabine–total-body irradiation (Flu-TBI) at 12 days prior to allo-HCT. Patients in the conventional care group received salvage chemotherapy followed by standard-of-care allo-HCT if they achieved complete remission/complete remission with incomplete platelet recovery. Patients in the conventional care group without complete remission/complete remission with incomplete platelet recovery could cross over to receive I-131–apamistamab and Flu-TBI prior to alloHCT.
Initial response was assessed 28 to 56 days after allo-HCT in the I-131–apamistamab group and 28 to 42 days after salvage chemotherapy initiation in the conventional care group. The primary outcome measure was durable complete remission lasting 180 days after initial complete remission/complete remission with incomplete platelet recovery.
Key Findings
In the intention-to-treat population, durable complete remission was observed in 17.1% (95% confidence interval [CI] = 9.4%–27.5%) of the I-131–apamistamab group vs 0% (95% CI = 0%–4.7%) of the conventional care group (P < .0001). Among 44 patients in the conventional care group who crossed over to receive I-131–apamistamab, 42 received I-131–apamistamab and allo-HCT; of these, 6 patients (13.6%) had durable complete remission.
In the intention-to-treat population, median overall survival was 6.3 months in the I-131–apamistamab group vs 5.9 months in the conventional care group (hazard ratio [HR] = 0.99, 95% CI = 0.70–1.41, P = .96). Among patients who crossed over to receive I-131–apamistamab, median overall survival was 7.1 months, compared with 3.2 months among those who did not cross over (HR = 0.53, 95% CI = 0.33–0.86). In the intention-to-treat population, median event-free survival was 3.2 vs 0 months (HR = 0.23, 95% CI = 0.15–0.34, P = .0001).
Grade ≥ 3 treatment-related adverse events occurred in 59.7% of the I-131–apamistamab group and 59.2% of the conventional care group.
The investigators concluded “The [I-131]-apamistamab–led regimen was associated with a higher [durable complete response rate] than conventional care in older patients with [relapsed or refractory acute myeloid leukemia]. [I-131]-apamistamab was well tolerated and could address an unmet need in this population.”
Sergio Giralt, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Actinium Pharmaceuticals. For full disclosures of the study authors, visit ascopubs.org.
