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

Autor:	Gyurkocza B; David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center, New York, NY., Nath R; Banner MD Anderson Cancer Center, Gilbert, AZ., Seropian S; Yale University School of Medicine-Yale Cancer Center, New Haven, CT., Choe H; The Ohio State University, Columbus, OH., Litzow MR; Mayo Clinic, Rochester, MN., Abboud C; Washington University School of Medicine, St Louis, MO., Koshy N; Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, TX., Stiff P; Loyola University Medical Center, Maywood, IL., Tomlinson B; University Hospitals Cleveland Medical Center, Cleveland, OH., Abhyankar S; University of Kansas Cancer Center, Kansas City, KS., Foran J; Mayo Clinic, Jacksonville, FL., Hari P; Froedtert Hospital and the Medical College of Wisconsin, Milwaukee, WI., Chen G; Roswell Park Comprehensive Cancer Center, Buffalo, NY.; MD Anderson Cancer Center, Houston, TX., Al-Kadhimi Z; University of Nebraska Medical Center, Omaha, NE., Kebriaei P; MD Anderson Cancer Center, Houston, TX., Sabloff M; University of Ottawa and The Ottawa Hospital Research Institute, Ottawa, ON, Canada., Orozco JJ; Fred Hutchinson Cancer Center and University of Washington School of Medicine, Seattle, WA., Jamieson K; University of North Carolina (UNC), Chapel Hill, NC., Silverman M; University of Iowa, Iowa City, IA., Van Besien K; Weill Cornell Medical College, New York, NY., Schuster M; Stony Brook University Cancer Center, Stony Brook, NY., Law AD; Hans Messner Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, Toronto, ON, Canada., Larkin K; The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH., Pandit-Taskar N; Department of Radiology, Memorial Sloan Kettering, New York, NY., Rowley SD; Hackensack University Medical Center, Hackensack, NJ., Munshi P; MedStar Georgetown University Hospital, Washington, DC., Cook R; Oregon Health & Science University, Portland, OR., Levy MY; Baylor Scott & White Health, Dallas, TX., Lazarus HM; Case Western Reserve University, Cleveland, OH., Sandmaier BM; Fred Hutchinson Cancer Center and University of Washington School of Medicine, Seattle, WA., Pagel JM; Loxo Oncology at Lilly, Stamford, CT., Reddy V; D2V Clinical, Raleigh, Durham, NC., MacDougall J; Statistical Consultant to Actinium Pharmaceuticals, New York, NY., McNamara K; Actinium Pharmaceuticals, New York, NY., Spross J; Actinium Pharmaceuticals, New York, NY., Haeuber E; Actinium Pharmaceuticals, New York, NY., Vusirikala M; Actinium Pharmaceuticals, New York, NY., Nahar A; Actinium Pharmaceuticals, New York, NY., Desai A; Actinium Pharmaceuticals, New York, NY., Giralt S; David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center, New York, NY.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2024 Sep 19, pp. JCO2302018. Date of Electronic Publication: 2024 Sep 19.
DOI:	10.1200/JCO.23.02018
Abstrakt:	Purpose: 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 131 I-apamistamab with conventional care. Methods: 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 131 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 131 I-apamistamab group and 28-42 days after salvage chemotherapy initiation; patients without CR/CRp or with AML progression could cross over to receive 131 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. Results: The ITT population included 153 patients ( 131 I-apamistamab [n = 76]; conventional care [n = 77]). In total, 44/77 conventional care arm patients crossed over and 40/77 (52%) received 131 I-apamistamab and alloHCT, with six patients (13.6%) experiencing a dCR. In the ITT population, the dCR rate was significantly higher with 131 I-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 131 I-apamistamab. Grade ≥3 treatment-related adverse events occurred in 59.7% and 59.2% of the 131 I-apamistamab and conventional care groups, respectively. Conclusion: The 131 I-apamistamab-led regimen was associated with a higher dCR rate than conventional care in older patients with RR AML. 131 I-apamistamab was well tolerated and could address an unmet need in this population.
Databáze:	MEDLINE
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