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

• Published in: Journal of clinical oncology p. JCO2302018
• Main Authors: Gyurkocza, Boglarka, Nath, Rajneesh, Seropian, Stuart, Choe, Hannah, Litzow, Mark R, Abboud, Camille, Koshy, Nebu, Stiff, Patrick, Tomlinson, Benjamin, Abhyankar, Sunil, Foran, James, Hari, Parameswaran, Chen, George, Al-Kadhimi, Zaid, Kebriaei, Partow, Sabloff, Mitchell, Orozco, Johnnie J, Jamieson, Katarzyna, Silverman, Margarida, Van Besien, Koen, Schuster, Michael, Law, Arjun Datt, Larkin, Karilyn, Pandit-Taskar, Neeta, Rowley, Scott D, Munshi, Pashna, Cook, Rachel, Levy, Moshe Y, Lazarus, Hillard M, Sandmaier, Brenda M, Pagel, John M, Reddy, Vijay, MacDougall, James, McNamara, Kathleen, Spross, Jennifer, Haeuber, Elaina, Vusirikala, Madhuri, Nahar, Akash, Desai, Avinash, Giralt, Sergio
• Format: Journal Article
• Language: English
• Published: United States 19.09.2024
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.23.02018

Older 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 I-apamistamab with conventional care. SIERRA (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 I-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 I-apamistamab group and 28-42 days after salvage chemotherapy initiation; patients without CR/CRp or with AML progression could cross over to receive I-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. The ITT population included 153 patients ( I-apamistamab [n = 76]; conventional care [n = 77]). In total, 44/77 conventional care arm patients crossed over and 40/77 (52%) received I-apamistamab and alloHCT, with six patients (13.6%) experiencing a dCR. In the ITT population, the dCR rate was significantly higher with I-apamistamab (17.1% [95% CI, 9.4 to 27.5]) than conventional care (0% [95% CI, 0 to 4.7]; < .0001). The OS hazard ratio (HR) was 0.99 (95% CI, 0.70 to 1.41; = .96), and the EFS HR was 0.23 (95% CI, 0.15 to 0.34), with HR <1 favoring I-apamistamab. Grade ≥3 treatment-related adverse events occurred in 59.7% and 59.2% of the I-apamistamab and conventional care groups, respectively. The I-apamistamab-led regimen was associated with a higher dCR rate than conventional care in older patients with RR AML. I-apamistamab was well tolerated and could address an unmet need in this population.