Treatment With 131L-Apamistamab Before AlloHCT Demonstrates Efficacy, Safety Among Older Patients With R/R AML

Phase 3 Results from the SIERRA Trial

Phase 3 results from the SIERRA trial demonstrated that anti-CD45 radioconjugate ¹³¹I-apamistamab before allogeneic hematopoietic cell transplantation (alloHCT) was well-tolerated and was associated with a higher durable complete remission (dCR) rate than standard care among older patients with relapsed/refractory (R/R) acute myeloid leukemia (AML).

“Older patients with R/R AML have dismal prognoses without allogeneic hematopoietic cell transplantation (alloHCT). SIERRA compared a targeted pretransplant regimen involving the anti-CD45 radioconjugate ¹³¹I-apamistamab with conventional care,” stated first study author Boglarka Gyurkocza, MD, Memorial Sloan Kettering Cancer Center, New York, New York, and coauthors.

This open-label trial included 153 patients (¹³¹I-apamistamab [n = 76]; conventional care [n = 77]) in the intention-to-treat (ITT) population. Eligible participants included those aged ≥55 years with active R/R AML who were randomly assigned on a 1-to-1 basis to either an ¹³¹I-apamistamab–led regimen before alloHCT or conventional care followed by alloHCT if initial complete remission (CR)/CR with incomplete platelet recovery (CRp) occurred.

The initial response was assessed 28 to 56 days after alloHCT in the ¹³¹I-apamistamab arm and 28 to 42 days after salvage chemotherapy initiation. Additionally, patients without CR/CRp or with AML progression could cross over to receive ¹³¹I-apamistamab followed by alloHCT. The primary end point measured in this study was durable complete remission (dCR) lasting 180 days after initial CR/CRp. Secondary end points included overall survival (OS) and event-free survival (EFS), assessed hierarchically in the ITT population.

Study results demonstrated 44 of 77 conventional care arm patients crossed over and 40 of 77 (52%) patients received ¹³¹I-apamistamab and alloHCT, with 6 patients (13.6%) experiencing a dCR. In the ITT population, the dCR rate was significantly higher with ¹³¹I-apamistamab (17.1% [95% (confidence interval) CI, 9.4 to 27.5]) than conventional care (0% [95% CI, 0 to 4.7]; P < .0001). The OS hazard ratio (HR) was 0.99 (95% CI, 0.70 to 1.41; P = .96), and the EFS HR was 0.23 (95% CI, 0.15 to 0.34), with a  HR of <1 favoring ¹³¹I-apamistamab.

Furthermore, the safety profile measured grade ≥3 treatment-related adverse events occurring in 59.7% and 59.2% of the ¹³¹I-apamistamab and conventional care groups, respectively.

“The ¹³¹I-apamistamab–led regimen was associated with a higher dCR rate than conventional care in older patients with R/R AML,” concluded Dr Gyurkocza and colleagues.

They also noted that “¹³¹I-apamistamab was well-tolerated and had the potential to address an unmet need in this patient population.

Source:

Gyurkocza B, Nath R, Seropian S, et al. Randomized phase 3 SIERRA trial of 131I-apamistamab before allogeneic hematopoietic cell transplantation versus conventional care for relapsed/refractory AML. J Clin Onc. Published online September 19, 2024. doi: 10.1200/JCO.23.02018