Randomized Phase III SIERRA Trial of 131I-Apamistamab Before Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care for Relapsed/Refractory AML Journal Article
| Authors: | Gyurkocza, B.; Nath, R.; Seropian, S.; Choe, H.; Litzow, M. R.; Abboud, C.; Koshy, N.; Stiff, P.; Tomlinson, B.; Abhyankar, S.; Foran, J.; Hari, P.; Chen, G.; Al-Kadhimi, Z.; Kebriaei, P.; Sabloff, M.; Orozco, J. J.; Jamieson, K.; Silverman, M.; Van Besien, K.; Schuster, M.; Law, A. D.; Larkin, K.; Pandit-Taskar, N.; Rowley, S. D.; Munshi, P.; Cook, R.; Levy, M. Y.; Lazarus, H. M.; Sandmaier, B. M.; Pagel, J. M.; Reddy, V.; MacDougall, J.; McNamara, K.; Spross, J.; Haeuber, E.; Vusirikala, M.; Nahar, A.; Desai, A.; Giralt, S. |
| Article Title: | Randomized Phase III SIERRA Trial of 131I-Apamistamab Before Allogeneic Hematopoietic Cell Transplantation Versus Conventional Care for Relapsed/Refractory AML |
| 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. © 2024 American Society of Clinical Oncology. |
| Keywords: | adult; controlled study; event free survival; aged; middle aged; survival rate; transplantation, homologous; major clinical study; leukemia, myeloid, acute; clinical trial; mortality; randomized controlled trial; clinical protocol; hematopoietic stem cell transplantation; radioactive iodine; iodine radioisotopes; multicenter study; graft versus host reaction; hematopoietic cell; phase 3 clinical trial; graft rejection; drug therapy; calcineurin inhibitor; clinical laboratory; therapy; allotransplantation; antibody conjugate; immunoconjugates; acute myeloid leukemia; procedures; mycophenolate mofetil; palliative chemotherapy; humans; human; male; female; article; delayed graft function; apamistamab i 131 |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 43 |
| Issue: | 2 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2025-01-01 |
| Start Page: | 201 |
| End Page: | 213 |
| Language: | English |
| DOI: | 10.1200/jco.23.02018 |
| PUBMED: | 39298738 |
| PROVIDER: | scopus |
| PMCID: | PMC11709001 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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