A phase III trial, named SIERRA, has revealed that the anti-CD45 radioconjugate iodine-131 apamistamab (I-131 apamistamab) significantly improves durable complete remission rates compared to conventional care in patients aged 55 years and older with relapsed or refractory acute myeloid leukemia (AML) prior to allogeneic hematopoietic cell transplantation (allo-HCT). The study, published in the Journal of Clinical Oncology, highlights a potential new approach for this challenging patient population.
Study Design and Key Findings
The open-label trial randomized 153 patients across 22 North American sites between February 2017 and October 2021. Patients were assigned to receive either I-131 apamistamab followed by fludarabine-total body irradiation (Flu-TBI) before allo-HCT (n=76) or conventional salvage chemotherapy followed by allo-HCT if they achieved complete remission (n=77). Patients in the conventional care arm who did not achieve complete remission were allowed to cross over to receive I-131 apamistamab and Flu-TBI prior to allo-HCT.
The primary outcome was durable complete remission, defined as lasting 180 days after initial complete remission. Results showed that 17.1% (95% CI = 9.4%-27.5%) of patients in the I-131 apamistamab group achieved durable complete remission, compared to 0% (95% CI = 0%-4.7%) in the conventional care group (P < .0001).
Median overall survival in the intention-to-treat population was 6.3 months in the I-131 apamistamab group and 5.9 months in the conventional care group (HR = 0.99, 95% CI = 0.70-1.41, P = .96). However, among the 44 patients who crossed over to receive I-131 apamistamab, median overall survival was 7.1 months, compared to 3.2 months for those who did not cross over (HR = 0.53, 95% CI = 0.33-0.86). Median event-free survival was 3.2 months vs 0 months (HR = 0.23, 95% CI = 0.15-0.34, P = . 0001).
Safety and Tolerability
Grade ≥ 3 treatment-related adverse events occurred in 59.7% of the I-131 apamistamab group and 59.2% of the conventional care group, indicating comparable tolerability between the two approaches.
Clinical Implications
The study's investigators concluded that the I-131 apamistamab-led regimen was associated with a significantly higher durable complete response rate than conventional care in older patients with relapsed or refractory AML. They also noted that I-131 apamistamab was well-tolerated and could address an unmet need in this population. According to Sergio Giralt, MD, of Memorial Sloan Kettering Cancer Center, the corresponding author for the Journal of Clinical Oncology article, this novel approach offers a potential new option for patients with limited treatment alternatives.
