Randomized Phase III SIERRA Trial of <sup>131</sup> I-Apamistamab Before Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care for Relapsed/Refractory AML
Abstract
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.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (40)
Boglarka Gyurkocza
1Memorial Sloan Kettering Cancer Center, Adult Bone Marrow Transplantation, Department of Medicine, New York, United States
Rajneesh Nath
Banner MD Anderson Cancer Center, Gilbert, Arizona, United States
Stuart Seropian
Hannah Choe
2The Ohio State University Comprehensive Cancer Center - James Cancer Hospital, Columbus, United States
Mark R. Litzow
Mayo Clinic
Camille Abboud
12Washington University School of Medicine, St Louis, United States
Nebu Koshy
7Baylor Scott & White Health, Dallas, United States
Patrick Stiff
1Loyola University Medical Center, Maywood, United States
Benjamin Tomlinson
University Hospitals Cleveland Medical Center, Cleveland, OH
Sunil Abhyankar
2University of Kansas Medical Center, Division of Hematology and Oncology, Kansas City, United States
James Foran
6Mayo Clinic Comprehensive Cancer Center, Jacksonville, United States
Parameswaran Hari
2Medical College of Wisconsin, Milwaukee, United States
George Chen
Department of Chemistry Virginia Tech Blacksburg Virginia USA
Zaid Al-Kadhimi
University of Alabama at Birmingham, Birmingham, AL
Partow Kebriaei
MD Anderson Cancer Center
Mitchell Sabloff
5The Ottawa Hospital, Ottawa, Canada
Johnnie J. Orozco
Fred Hutchinson Cancer Research Center, Seattle, WA
Katarzyna Jamieson
14University of North Carolina Hospitals, Chapel Hill, United States
Margarida Silverman
University of Iowa, Iowa City, IA
Koen van Besien
Seidman Cancer Center, Cleveland, Ohio, United States
Michael Schuster
1Stony Brook University Hospital, Division of Hematology and Oncology, Stony Brook, United States
Arjun Datt Law
Princess Margaret Cancer Centre, Toronto, ON, Canada
Karilyn Larkin
17Ohio State University Hospital, Columbus, United States
Neeta Pandit-Taskar
Memorial Sloan Kettering Cancer Center, New York, NY
Scott D. Rowley
Hackensack University Medical Center, Hackensack, NJ
Pashna Munshi
1MedStar Georgetown University Hospital, Stem Cell Transplant and Cellular Immunotherapy Program, Washington, United States
Rachel Cook
1Oregon Health and Science University, Portland, United States
Moshe Y. Levy
Baylor Scott & White Health, Dallas, TX
Hillard M. Lazarus
Case Western Reserve University, Cleveland, OH
Brenda M. Sandmaier
2Division of Hematology and Oncology, University of Washington School of Medicine, Seattle, WA
John M. Pagel
10Swedish Cancer Institute, Seattle, WA
Vijay Reddy
D2V Clinical, Raleigh, Durham, NC
James MacDougall
Statistical Consultant to Actinium Pharmaceuticals, New York, NY
Kathleen McNamara
Actinium Pharmaceuticals, New York, NY
Jennifer Spross
Actinium Pharmaceuticals, New York, NY
Elaina Haeuber
Premier Research, Philadelphia, PA
Madhuri Vusirikala
Actinium Pharmaceuticals, New York, NY
Akash Nahar
4Daiichi Sankyo Inc., Basking Ridge, United States
Avinash Desai
Actinium Pharmaceuticals, New York, NY
Sergio Giralt
1Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY