TY - JOUR
T1 - Randomized Phase III SIERRA Trial of 131I-Apamistamab before Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care for Relapsed/Refractory AML
AU - Gyurkocza, Boglarka
AU - Nath, Rajneesh
AU - Seropian, Stuart
AU - Choe, Hannah
AU - Litzow, Mark R.
AU - Abboud, Camille
AU - Koshy, Nebu
AU - Stiff, Patrick
AU - Tomlinson, Benjamin
AU - Abhyankar, Sunil
AU - Foran, James
AU - Hari, Parameswaran
AU - Chen, George
AU - Al-Kadhimi, Zaid
AU - Kebriaei, Partow
AU - Sabloff, Mitchell
AU - Orozco, Johnnie J.
AU - Jamieson, Katarzyna
AU - Silverman, Margarida
AU - Van Besien, Koen
AU - Schuster, Michael
AU - Law, Arjun Datt
AU - Larkin, Karilyn
AU - Pandit-Taskar, Neeta
AU - Rowley, Scott D.
AU - Munshi, Pashna
AU - Cook, Rachel
AU - Levy, Moshe Y.
AU - Lazarus, Hillard M.
AU - Sandmaier, Brenda M.
AU - Pagel, John M.
AU - Reddy, Vijay
AU - MacDougall, James
AU - McNamara, Kathleen
AU - Spross, Jennifer
AU - Haeuber, Elaina
AU - Vusirikala, Madhuri
AU - Nahar, Akash
AU - Desai, Avinash
AU - Giralt, Sergio
N1 - Publisher Copyright:
© 2024 American Society of Clinical Oncology.
PY - 2025/1/10
Y1 - 2025/1/10
N2 - PURPOSEOlder patients with relapsed or refractory AML (RR 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.METHODSSIERRA (ClinicalTrials.gov identifier: NCT02665065) was a phase III open-label trial. Patients age ≥55 years with active RR AML were randomly assigned 1:1 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. Initial response was assessed 28-56 days after alloHCT in the 131I-apamistamab group and 28-42 days after salvage chemotherapy initiation; patients without CR/CRp or with AML progression could cross over to receive 131I-apamistamab followed by alloHCT. The primary end point was durable complete remission (dCR) lasting 180 days after initial CR/CRp. Secondary end points were overall survival (OS) and event-free survival (EFS), assessed hierarchically in the intention-to-treat (ITT) population.RESULTSThe ITT population included 153 patients (131I-apamistamab [n = 76]; conventional care [n = 77]). In total, 44/77 conventional care arm patients crossed over and 40/77 (52%) received 131I-apamistamab and alloHCT, with six patients (13.6%) experiencing a dCR. In the ITT population, the dCR rate was significantly higher with 131I-apamistamab (17.1% [95% 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 HR <1 favoring 131I-apamistamab. Grade ≥3 treatment-related adverse events occurred in 59.7% and 59.2% of the 131I-apamistamab and conventional care groups, respectively.CONCLUSIONThe 131I-apamistamab-led regimen was associated with a higher dCR rate than conventional care in older patients with RR AML. 131I-apamistamab was well tolerated and could address an unmet need in this population.
AB - PURPOSEOlder patients with relapsed or refractory AML (RR 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.METHODSSIERRA (ClinicalTrials.gov identifier: NCT02665065) was a phase III open-label trial. Patients age ≥55 years with active RR AML were randomly assigned 1:1 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. Initial response was assessed 28-56 days after alloHCT in the 131I-apamistamab group and 28-42 days after salvage chemotherapy initiation; patients without CR/CRp or with AML progression could cross over to receive 131I-apamistamab followed by alloHCT. The primary end point was durable complete remission (dCR) lasting 180 days after initial CR/CRp. Secondary end points were overall survival (OS) and event-free survival (EFS), assessed hierarchically in the intention-to-treat (ITT) population.RESULTSThe ITT population included 153 patients (131I-apamistamab [n = 76]; conventional care [n = 77]). In total, 44/77 conventional care arm patients crossed over and 40/77 (52%) received 131I-apamistamab and alloHCT, with six patients (13.6%) experiencing a dCR. In the ITT population, the dCR rate was significantly higher with 131I-apamistamab (17.1% [95% 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 HR <1 favoring 131I-apamistamab. Grade ≥3 treatment-related adverse events occurred in 59.7% and 59.2% of the 131I-apamistamab and conventional care groups, respectively.CONCLUSIONThe 131I-apamistamab-led regimen was associated with a higher dCR rate than conventional care in older patients with RR AML. 131I-apamistamab was well tolerated and could address an unmet need in this population.
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U2 - 10.1200/JCO.23.02018
DO - 10.1200/JCO.23.02018
M3 - Article
C2 - 39298738
AN - SCOPUS:85205359562
SN - 0732-183X
VL - 43
SP - 201
EP - 213
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 2
ER -