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598 HCT-Adapted ELN 2022 Risk Classification: Validation of a Very Poor Risk Group (Adverse-Plus) in AML Patients Undergoing Allogeneic Hematopoietic Cell Transplantation. Study on Behalf of the Grupo Español De Trasplante y Terapia Celular (GETH-TC)

Program: Oral and Poster Abstracts
Type: Oral
Session: 723. Allogeneic Transplantation: Long-Term Follow up and Disease Recurrence: Long-term Outcomes Including in Bone Marrow Failure and Rare Diseases
Hematology Disease Topics & Pathways:
AML, Research, Acute Myeloid Malignancies, Clinical Research, Diseases, Treatment Considerations, Registries, Myeloid Malignancies, Human
Sunday, December 8, 2024: 12:45 PM

Carlos Jimenez-Vicente1,2*, Maria Queralt Salas1,3*, Jordi Esteve, MD, PhD4,5, Monica Baile Gonzalez6*, Carmen Martin Calvo, MD7*, Itziar Oiartzabal Ormategui, MD8*, Albert Esquirol, MD9*, Felipe Peña, MD10,11*, Sara Fernandez-Luis, MD12*, Inmaculada Heras, MD13*, Ana Pilar Gonzalez-Rodriguez14*, Alberto Lopez Garcia, MD15, Tamara Torrado, MD16*, Adolfo Jesús Sáez Marín, MD17*, Cynthia Acosta Fleitas, PhD18*, Lucia García Mañó19*, Sara Villar, MD20*, Silvia Filafferro21*, Pascual Basalobre22* and Maria Jesús Pascual, MD23*

1Hematopoietic Cell Transplantation Unit, Hospital Clínic de Barcelona, ICHMO, Barcelona, Spain
2Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS),, Barcelona, Spain
3Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Spain
4Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Spain
5Hematology Department, Hospital Clínic Barcelona, ICAMS, Barcelona, Spain
6Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC), Salamanca, Spain
7Hospital Universitario Reina Sofía, Cordoba, Spain
8Hematology Department, Hospital Universitario de Donosti, Donosti, Spain
9Hematology and Hemotherapy Department, Hospital de la Sant Creu i Sant Pau. IIB-Sant Pau and José Carreras Leukemia Research Institutes. Universitat Autónoma de Barcelona, Barcelona, Spain
10Clinical Hematology Department, Institut Català d’Oncologia-Hospitalet, IDIBELL, Barcelona, Spain
11Institut Català d'Oncologia - Hospital Duran i Reynals, Barcelona, Spain
12Hospital Universitario Marqués de Valdecilla (IDIVAL), Santander, Spain
13Hematology Division, Hospital Morales Meseguer, Murcia, Spain
14Hospital Universitario Central de Asturias, Oviedo, Spain
15Fundacion Jimenez Diaz University Hospital, Madrid, Spain
16Hospital Universitario de A Coruña, A Coruña, Spain
17Servicio de Hematología, Hospital 12 de Octubre, Madrid, Madrid, Spain
18Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas, ESP
19Hematology Department., Hospital Universitario Son Espases, IdISBa., Palma, Spain
20Hematology and Cell Therapy Department. Clinica Universidad de Navarra. IdiSNA., Pamplona, Spain
21Grupo EspañOl De Trasplante De Progenitores HematopoyéTicos Y Tera, Madrid, ESP
22Grupo Español de Trasplante de Progenitores Hematopoyéticos y Terapia Celular, Madrid, Spain
23Hematology Department, Hospital Regional Universitario de Málaga, Málaga, Spain

Background

In 2022, the European LeukemiaNet (ELN) updated its guidelines for risk allocation in acute myeloid leukemia (AML) patients (Döhner H et al., Blood 2022). Subsequently, a few studies validated externally the prognostic value of this new classification in allografted patients (Jentzsch M et al., Blood Cancer J., 2022 and Jiménez-Vicente C et al, B J Haem 2024). The latter identified a new subgroup, Adverse-Plus (AdvP), with worse outcome if MECOM (EVI1) rearrangement, complex karyotype (CK), TP53 mutation and/or del(17p) were present at AML diagnosis (HCT-Adapted ELN classification)

Methods

This multicenter, retrospective study aims to validate the prognosis ability of the new ELN risk classification with the consideration of the new the subgroup category recently proposed by Jiménez-Vicente C, in AML patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) at 16 Spanish GETH-TC institutions. The study included 651 AML patients who underwent their first allo-HCT in complete morphological response (CR) between 2015 and 2023. All patients achieved CR after at least one line of anthracycline-based induction intensive chemotherapy, with genetic information recorded at diagnosis. Data were updated in May 2024.

Patients were initially categorized into favorable (Fav), intermediate (Int), and adverse (Adv) ELN risk groups based on genetic information. Subsequently, those in the Adv group were further divided into the Adv* and AdvP groups based on the previously mentioned criteria (HCT-Adapted ELN 2022 classification).

Results

The median age of the cohort was 55 years (range 17-74); 52.6% were male, and 84.9% underwent allo-HCT in first CR. Thirty-nine percent of the patients received myeloablative regimens (MAC), and 51.9% received PTCY-based prophylaxis. Grafts were sourced from HLA-matched donors (67.6%), HLA-mismatched unrelated donors (7.4%), and haploidentical donors (28.7%).

According to the HCT-Adapted ELN 2022 classification, 126 patients (19.4%) were in the Fav group, 248 (38.1%) in the Int group, 177 (27.2%) in the Adv group, and 100 (15.4%) in the AdvP group. Baseline characteristics between subgroups were investigated. Compared with the Fav group, AdvP patients were older (median age 58 vs. 53 years, p < 0.001), underwent allo-HCT in first CR (92% vs. 58.7% (p < 0.001).

During follow-up 28.4% of the patients relapsed and 34.5% died. The 2-year overall survival (OS) and leukemia-free survival (LFS) were 80.5% and 71.5% for the Fav group, 72.5% and 66.7% for the Int group, 72.3% and 63.5% for Adv* group, and 37.8% and 32.3% for the AdvP group.

A multivariate regression analysis (MVA) including relevant variables for the allo-HCT [age <55 years (vs. younger), AML type (De novo vs. Secondary/Therapy-Related), MRD positive status prior to allo-HCT (vs. negative), reduced intensity conditioning regimen (vs. myeloablative) PTCY-prophylaxis (vs. others), HLA-matched donor (vs. others) and first CR (vs. others)] confirmed the poor prognosis of the AdvP group. Compared with the Adv* group, patients within the AdvP group had lower OS (HR: 3.05, p < 0.001) and LFS (HR: 2.66, p < 0.001). Age >55 years (OS (HR: 1.72, p = 0.002), LFS (HR: 1.41, p = 0.011) and a positive MRD status prior to allo-HCT (OS (HR: 1.49, p = 0.007), LFS (HR: 1.51, p = 0.002) were associated with lower OS and LFS. Interestingly, the outcome of Adv* risk patients was similar to Int (OS (HR: 1.02, p = 0.90), LFS (HR: 1.17, p = 0.37)

Further investigations were conducted among the 100 patients in the AdvP group, based on genetic abnormalities identified at diagnosis. Of these patients, 22% had MECOM(EVI1) rearrangements, and 78% had a CK and/or TP53 mutations. Within this subgroup, 62% of the patients relapsed and 67% died. Furthermore, the estimated 2-year OS and LFS were 51% and 40% for patients with MECOM(EVI1) rearrangements, and 34% (p = 0.04) and 30% (p = 0.07) for those with CK and/or TP53 mutations.

Conclusion

The study validates the ELN 2022 risk classification as a prognostic marker for allo-HCT outcomes in AML patients in CR, confirming also the poorer outcome in the Adv group, attributable to patients subclassified under the new AdvP risk category. This information provides relevant information on relapse risk after allo-HCT, facilitate patient counseling, and warrants the design of specific transplant strategies for this AdvP subgroup to prevent post-transplant relapse.

Disclosures: Jimenez-Vicente: AbbVie: Speakers Bureau; AbbVie: Other: Travel Grants.

*signifies non-member of ASH