Abstract
AML-521 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
Clinical lymphoma, myeloma and leukemia, Vol.23(Suppl. 1), pp.S309-S310
09/2023
DOI: 10.1016/S2152-2650(23)01076-5
Abstract
Background
Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) have dismal outcomes, and <20% undergo allogeneic hematopoietic stem cell transplantation (alloHSCT). Those with venetoclax failure have worse outcomes (median survival, 2–3 months) without alloHSCT. SIERRA investigated the use of iodine-131 apamistamab (Iomab-B), a 131I-labeled anti–cluster of differentiation (CD)-45 monoclonal antibody, to enable alloHSCT in patients with active R/R AML; Iomab-B was compared with conventional care (CC).
Aim
To report outcomes from SIERRA patients with failed targeted therapies.
Methods
Patients >55 years of age with R/R AML were randomized (1:1) to receive Iomab-B followed by fludarabine, total body irradiation (2 Gy), and alloHSCT or 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.
Results
Of 153 patients, 94 (61%) received targeted therapies, including inhibitors of B-cell lymphoma 2 (BCL-2; venetoclax; 65%), fms-like tyrosine kinase 3 (FLT-3; 24%), and isocitrate dehydrogenase (IDH; 10%) prior to randomization, with a balanced distribution between groups. In the CC group, 27 (35%) received targeted therapies as salvage prior to alloHSCT; of those, 7 (26%) responded and received alloHSCT. Eleven of 20 nonresponders (55%) crossed over to receive Iomab-B followed by alloHSCT. All patients who received Iomab-B (n=66) underwent alloHSCT vs 14 (18.2%) in the CC group. Of evaluable patients (Iomab, 59; CC, 64), durable complete remission (dCR) was achieved in 13 (22%) vs 0. Of the 13 dCR patients, 10 (77%) had prior targeted-therapy failure and 7 (54%) had venetoclax failure; 1-year survival was 90% (9/10) in all prior targeted therapy–failure patients and 85% (6/7) in those with prior venetoclax failure. The overall safety of the groups with and without prior targeted therapy was comparable.
Conclusion
Patients with failure of targeted therapies, including venetoclax, were able to undergo alloHSCT with the Iomab-B–led regimen. Of those who achieved dCR with Iomab-B, >70% had previous targeted-therapy failure, including >50% with previous venetoclax failure. The majority of dCR patients were long-term survivors. Iomab-B significantly improves outcomes in patients with prior targeted-therapy failure. (www.sierratrial. com or clinicaltrials.gov NCT02665065).
Details
- Title: Subtitle
- AML-521 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
- Creators
- Rajneesh NathStuart SeropianHannah ChoeMark R. LitzowCamille AbboudNebu KoshyPatrick J. StiffBenjamin TomlinsonSunil AbhyankarJames M. ForanParameswaran HariGeorge L. ChenZaid S. Al-KadhimiPartow KebriaeiMitchell SabloffJohnnie J. OrozcoKatarzyna JamiesonMargarida Magalhaes-SilvermanKoen Van BesienMichael SchusterArjun LawSameem AbedinKarilyn LarkinScott RowleyPashna MunshiRachel CookSebastian MayerMoshe Yair LevyHillard M. LazarusBrenda M. SandmaierVijay ReddyJennifer SprossKathleen McNamaraElaina HaeuberMadhuri VusirikalaAkash NaharJohn M. PagelSergio A. GiraltAvinash DesaiBoglarka Gyurkocza
- Resource Type
- Abstract
- Publication Details
- Clinical lymphoma, myeloma and leukemia, Vol.23(Suppl. 1), pp.S309-S310
- Publisher
- Elsevier Inc
- DOI
- 10.1016/S2152-2650(23)01076-5
- ISSN
- 2152-2650
- eISSN
- 2152-2669
- Language
- English
- Date published
- 09/2023
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984461351002771
Metrics
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