Randomized Phase III SIERRA Trial of 131I-Apamistamab before Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care for Relapsed/Refractory AML

Boglarka Gyurkocza, Rajneesh Nath, Stuart Seropian, Hannah Choe, Mark R. Litzow, Camille Abboud, Nebu Koshy, Patrick Stiff, Benjamin Tomlinson, Sunil Abhyankar, James Foran, Parameswaran Hari, George Chen, Zaid Al-Kadhimi, Partow Kebriaei, Mitchell Sabloff, Johnnie J. Orozco, Katarzyna Jamieson, Margarida Silverman, Koen Van BesienMichael Schuster, Arjun Datt Law, Karilyn Larkin, Neeta Pandit-Taskar, Scott D. Rowley, Pashna Munshi, Rachel Cook, Moshe Y. Levy, Hillard M. Lazarus, Brenda M. Sandmaier, John M. Pagel, Vijay Reddy, James MacDougall, Kathleen McNamara, Jennifer Spross, Elaina Haeuber, Madhuri Vusirikala, Akash Nahar, Avinash Desai, Sergio Giralt

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)201-213
Number of pages13
JournalJournal of Clinical Oncology
Volume43
Issue number2
DOIs
StatePublished - Jan 10 2025

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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