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4231 Acute Myeloid Leukemia with Inv(3) or t(3;3): A Clinical and Cytogenetic Characterization of 40 Patients

Program: Oral and Poster Abstracts
Session: 613. Acute Myeloid Leukemias: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, Acute Myeloid Malignancies, AML, adult, Clinical Research, health outcomes research, patient-reported outcomes, Diseases, Myeloid Malignancies, Study Population, Human
Monday, December 11, 2023, 6:00 PM-8:00 PM

Maria Moscvin, MD1*, Matthew Schwede, MD2, Gabriel N. Mannis2,3,4 and Tian Y. Zhang, MD, PhD2,5,6

1Stanford Healthcare, Palo Alto, CA
2Division of Hematology, Department of Medicine, Stanford University, Stanford, CA
3Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA
4Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA
5Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA
6Stanford Cancer Institute, Stanford, CA


Acute myeloid leukemia (AML) with inv(3) or t(3;3) is an extremely aggressive and rare subtype of AML. Leukemogenesis in inv(3) AML is in part due to juxtaposition of the GATA2 enhancer in close proximity to the MECOM/EVI1 promoter; as the result, the fusion drives EVI1 overexpression and uncontrolled proliferation of myeloid progenitors. Given its rarity, published clinical outcome data are limited. To improve our understanding of the clinical outcomes of inv(3) AML, we conducted a retrospective study to describe the clinical features of a cohort of newly diagnosed inv(3)/t(3;3) AML patients treated at Stanford Cancer Center between 2002 and 2023.


Data were retrospectively collected from databases associated with the Stanford Health Care electronic health record (EHR), and diagnosis dates came from the Stanford Cancer Registry. Inv(3)/t(3;3) AML diagnosis was defined according to WHO criteria as the presence of ≥20% blasts in the bone marrow (BM) or peripheral blood (PB) and the presence of inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2) on cytogenetic analysis at initial diagnosis. Response to first induction, salvage, and consolidation therapy as well as allogeneic hematopoietic stem cell transplant (alloHSCT) were captured. CR was defined as the presence of <5% of blasts in the BM evaluation by morphological evaluation after each line of treatment. Overall survival (OS) was defined as time from diagnosis to death from any cause. A descriptive study of the main demographic, clinical, hematologic, and cytogenetic variables of patients who received intensive and non-intensive therapy was performed. The analysis was performed using R 4.3.1. A p value of < 0.05 was defined to be statistically significant.


A total of 40 patients met inclusion criteria including 68% (n=27) with de novo AML, 25% (n=10) with secondary AML from an antecedent hematological disorder and 7.5% (n=3) therapy-related AML. Clinical characteristics of the patients are summarized in Figure 1A. The median age at time of diagnosis was 56 (range, 19-78). There was a slight female predominance, with 58% (n=23) female and 42% (n=17) males. Ninety-three percent of patients had an ECOG score 1 (n=37). Median leukocyte, hemoglobin, and platelet counts were 4.5 K/uL, [1.3-761], 9.4 g/dL, [3.4-13.6], and 98 K/uL [9-592], respectively. The median blast percentage in BM and PB was 49% [13-98] and 30% [0-95], respectively. Inv(3)/t(3;3) was the only cytogenetic aberration in 10 patients (25%) and chromosome (chr) 7 abnormalities were the most common additional aberration, present in 22 patients (55%). CR after the first induction therapy was achieved in 9 patients (22%); 6 patients (15%) died during or shortly after induction therapy, and the remaining 25 (63%) were resistant. Salvage therapies for patients included re-induction with 7+3, FLAG-Ida, mitoxantrone-containing regimens, clofarabine-based protocols, or combination of hypomethylating agents with venetoclax. Seventeen (43%) patients underwent alloHSCT (10 in CR and 7 with active disease). When comparing intensive vs non-intensive induction regimen, no statistical significance was identified for complete remission (CR) rate (p= 1.00), overall survival (OS) rate (p=0.65) or relapse-free survival (RFS) rate (p=0.86). Similarly, no statistically significant prognostic factors (age, WBC, BM blast %, platelet count, hemoglobin, ANC, or time to transplant) for OS were identified. Interestingly, chr 7 abnormalities in inv(3) patients conferred a worse prognosis in this cohort (OS 41% vs. 59%, p= 0.0064, Figure 1B). This association was confirmed using a multiple Cox proportional hazards regression adjusting for age and blast percentage. Moreover, while chr 7 abnormality was also associated with a lower response rate (CR 14% vs. 40%), it did not reach statistical significance (p=0.12).


In summary, de novo AML inv(3)/t(3;3) is a rare and aggressive subtype of AML conferring extremely poor prognosis. There appears to be an increase of incidence in females affecting a slightly younger demographic. Consistent with previous studies, the presence of chr 7 abnormalities was associated with even worse outcomes, which interestingly also drive EVI1 overexpression. The exact link between 3q26 loci rearrangements and chr 7 abnormalities warrants further investigation.

Disclosures: Mannis: Genentech: Consultancy; BMS/Celgene: Consultancy; Astellas: Consultancy; Macrogenics: Honoraria; Agios: Consultancy; Abbvie: Consultancy; Stemline: Consultancy. Zhang: Servier: Consultancy; Bristol Myers Squibb: Research Funding; Rigel: Consultancy; Abbvie: Consultancy; Stanford University: Current Employment.

*signifies non-member of ASH