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3235 Clinical Impact of the New Bone Marrow Blasts Cutoff Defined By the International Classification Consortium (ICC) in Myeloid Neoplasms with Mutated TP53 gene

Program: Oral and Poster Abstracts
Session: 637. Myelodysplastic Syndromes – Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
adult, MDS, AML, Acute Myeloid Malignancies, Research, elderly, Clinical Practice (Health Services and Quality), epidemiology, Clinical Research, Chronic Myeloid Malignancies, Diseases, patient-reported outcomes, real-world evidence, young adult , Myeloid Malignancies, survivorship, Human, Study Population
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Francisco Beas1*, Maria Sola, MD2*, Mar Tormo, M.D.3, Ana Riera, MD3*, Nicolas Diaz Varela, MD4*, Félix López Cadenas, MD5*, Nieves Garcia-Gisbert6*, Sara García, MD7*, Laura Palomo, PhD8*, Sandra Novoa Jáuregui, MD9*, Olga Salamero, MD10*, Ana Pérez-González, MD10*, Silvia Saumell, MD, PhD9*, Barbara Tazon, PhD11*, Laura Gallur, MD9*, Gloria Hidalgo-Gómez, PhD9*, Sara Torres-Esquius, MSc9*, Francesc Bosch, MD, PhD9, Andres Jerez, MD, PhD11*, Maria Julia Montoro, MD, PhD9* and David Valcarcel, MD, PhD9

1Experimental Hematology Unit, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, AL, Spain
2Department of Hematology, Vall d’Hebron University Hospital, University Autonoma of Barcelona (UAB), Barcelona, Spain, Barcelona, Spain
3Hospital Clínico Universitario de Valencia, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
4Santiago Clinic Hospital CHUS, Santiago De Compostela, ESP
5Servicio de Hematología, Hospital Del Mar, Barcelona, Spain
6IMIM-Hospital del Mar, Barcelona, Spain
7Hematology Department, Hospital del Mar, Barcelona, Spain
8Department of Hematology, Vall d'Hebron University Hospital, Barcelona, Spain
9Department of Hematology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain
10Hematology Department, Vall d'Hebron University Hospital, University Autònoma of Barcelona (UAB), Barcelona, Spain
11Hematology Department, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain

Introduction: The recent ICC introduced a novel category denominated “myeloid neoplasms with mutated TP53” (MN-TP53) that includes: 1) myelodysplastic syndromes (MDS-TP53) in cases with multi-hit TP53 or mutated TP53 with complex karyotype, and blasts <10%; 2) MDS/acute myeloid leukemia (MDS/AML-TP53) in those with TP53 mutations and blasts between 10-19% and 3) AML-TP53 in patients with TP53 mutations and blasts ≥ 20%. In all the aforementioned groups, a variant allele frequency (VAF) >10% of TP53 gene is required for inclusion. As opposite to ICC, the WHO 2022 classification does not recognize this mutated group as a distinct entity, maintaining the 20% blast count as the boundary between MDS and AML, with no intermediate category. The objective of this study was to assess, in a multicentric series, whether the 10% blast cutoff has clinical implications in the MN-TP53 category.

Methods: All patients diagnosed with MDS and AML with MN-TP53 criteria according to ICC between 2009-2023 were included from four Spanish centers. TP53 gene status was assessed by Next-Generation Sequencing.

Results: A total of 107 patients were included: 25 (23.4%) MDS-TP53, 17 (15.9%) MDS/AML-TP53, and 65 (60.7%) AML-TP53. The median age at diagnosis was 70 years (interquartile range, IQR: 65-78) and 54 (50.5%) were male. Among all patients, 83 (77.6%) presented a complex karyotype. After a median follow-up of 6.2 months, 84 patients (78.5%) died, resulting in a median overall survival (OS) of 7.9 months.

The median OS for the MDS-TP53, MDS/AML-TP53 and AML-TP53 groups was 12.9, 14.3 and 5.4 months, respectively (p=0.025) (Figure 1). Paired comparisons showed similar OS between MDS-TP53 and MDS/AML-TP53 groups (p=0.5) but shorter OS in AML-TP53 group when confronted with MDS/AML-TP53 (p=0.03) or AML-TP53 with MDS-TP53 (p=0.052).

In addition to potential outcome dissimilarities, clinical characteristics at baseline were also compared (Table 1). Again, there were no differences between the MDS-TP53 and MDS/AML-TP53 groups at diagnosis. Intensity of chemotherapy treatment and frequency of allogenic hematopoietic stem cell transplant (alloHSCT) were also analyzed. One important difference between MDS-TP53 and MDS/AML-TP53 was that 4% and 29% of cases underwent alloHSCT, respectively. To assess the potential impact of allotransplant in this cohort, the survival analysis was repeated censoring the OS at the infusion date. The OS between groups MDS-TP53 and MDS/AML remained comparable (p=0,98).

Conclusions: In our cohort, patients with MDS-TP53 and MDS/AML-TP53 exhibit similar clinical behavior, in contrast to AML-TP53, suggesting that the newly proposed 10% blasts cutoff is not adding clinical value to the management of these entities.

Disclosures: Tormo: Gilead: Honoraria; Pfizer: Honoraria; MSD: Honoraria; SOBI: Other: Participation on Data Safety Monitoring Board; Jannsen: Other: Support for attending meetings; BMS: Honoraria; Astellas: Honoraria; AbbVie: Honoraria; Jazz: Other: support for attending meetings. Salamero: Pfizer: Consultancy, Honoraria; Jazz: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Tazon: Bristol Myer Squibb: Honoraria. Bosch: Novartis: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Mundipharma: Consultancy, Honoraria; Lilly: Consultancy; Roche: Honoraria; BeiGene: Consultancy; AstraZeneca: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyospharm: Other; Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Jerez: GILEAD: Research Funding; Astrazeneca: Research Funding; Novartis: Consultancy; BMS: Consultancy.

*signifies non-member of ASH