KEY TAKEAWAYS
- The SIERRA phase III trial aimed to evaluate the outcomes of SIERRA trial participants with failed targeted therapies who underwent HCT following conditioning with Iomab-B.
- The study offered a promising new treatment option for R/R AML patients who have failed targeted therapies.
Iodine-131 apamistamab(Iomab-B), an iodine-labeled anti-CD45 monoclonal antibody, has shown promise in enabling allogeneic hematopoietic stem cell transplantation (alloHSCT) for relapsed or refractory (R/R) acute myeloid leukemia (AML) patients, particularly those who have previously failed venetoclax therapy.
Researchers aimed to evaluate the outcomes of SIERRA trial participants with failed targeted therapies who underwent HCT following conditioning with Iomab-B.
Patients aged >55 years with R/R AML were randomized (1:1) to receive Iomab-B followed by fludarabine, total body irradiation (2 Gy), and alloHSCT, or conventional care (CC) (physician’s choice of therapy, including targeted agents and alloHSCT if leukemia-free). Crossover to Iomab-B–based alloHSCT was permitted for CC patients with progression or without complete remission.
Of 153 patients, 94 (61%) received targeted therapies before randomization, including inhibitors of B-cell lymphoma 2 (BCL-2; venetoclax; 65%), fms-like tyrosine kinase 3 (FLT-3; 24%), and isocitrate dehydrogenase (IDH; 10%). In the CC group, 35% received salvage-targeted therapies before alloHSCT, with 26% responding and undergoing alloHSCT.
Among nonresponders, 55% crossed over to receive Iomab-B, followed by alloHSCT. All Iomab-B recipients (n=66) underwent alloHSCT vs 18.2% (14) in the CC group. In the evaluable patients(Iomab, 59; CC, 64), durable complete remission (dCR) was achieved in 22% (13/59) with Iomab-B vs 0 in the CC group. Among dCR patients, 77% had prior targeted-therapy failure, and 54% had venetoclax failure.
The 1-year survival rate was 90% (9/10) for all prior targeted therapy–failure patients and 85% (6/7) for those with prior venetoclax failure. Overall safety was comparable between groups with and without prior targeted therapy.
The study offered a promising new treatment option for R/R AML patients who have failed targeted therapies.
Source: https://clml-soho2023.elsevierdigitaledition.com/310/index.html
Clinical Trial: https://clinicaltrials.gov/study/NCT02665065
Nath R, Seropian S, Choe H, Litzow MR, Abboud C, Koshy N, Stiff PJ, Tomlinson B, Abhyankar S, Foran JM, Hari P, Chen GL, Al-Kadhimi ZS, Kebriaei P, Sabloff M, Orozco JJ, Jamieson K, Magalhaes-Silverman M, Van Besien K, Schuster M, Law A, Abedin S, Larkin K, Rowley S, Munshi P, Cook R, Mayer S, Levy MY, Lazarus HM, Sandmaier BM, Reddy V, Spross J, McNamara K, Haeuber E, Vusirikala M, Nahar A, Pagel JM, Giralt SA, Desai A, Gyurkocza B. The Randomized Phase III SIERRA (Study of Iomab‑B in Elderly Relapsed or Refractory AML) Trial: Successful Allogeneic Hematopoietic Stem Cell Transplantation Using Treatment With Iomab‑B‑Led Regimen for Patients With Active, Relapsed or Refractory AML With Failed Targeted Therapies.
