Outcomes of patients with bone marrow fibrosis in de novo and secondary acute myeloid leukemia.

person Samuel Urrutia The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Samuel Urrutia, Hagop M. Kantarjian, Farhad Ravandi-Kashani, Elias Jabbour, Rashmi Kanagal-Shamanna, Sanam Loghavi, Keyur P. Patel, Guillermo Montalban-Bravo, Nicholas James Short, Naval Guastad Daver, Gautam Borthakur, Courtney Denton Dinardo, Tapan M. Kadia, Lucia Masarova, Prithviraj Bose, Naveen Pemmaraju, Guillermo Garcia-Manero, Koji Sasaki

Authors person Samuel Urrutia The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Samuel Urrutia, Hagop M. Kantarjian, Farhad Ravandi-Kashani, Elias Jabbour, Rashmi Kanagal-Shamanna, Sanam Loghavi, Keyur P. Patel, Guillermo Montalban-Bravo, Nicholas James Short, Naval Guastad Daver, Gautam Borthakur, Courtney Denton Dinardo, Tapan M. Kadia, Lucia Masarova, Prithviraj Bose, Naveen Pemmaraju, Guillermo Garcia-Manero, Koji Sasaki Organizations The University of Texas MD Anderson Cancer Center, Houston, TX, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX Abstract Disclosures Research Funding No funding sources reported Background: The outcomes of patients with de novo acute myeloid leukemia (AML) with bone marrow fibrosis (MF) have not been systematically studied. Our objective was to define the prognosis of patients with AML and multiple degrees of bone marrow fibrosis, efficacy of therapy, and survival outcomes. Methods: We retrospectively evaluated 2302 patients diagnosed with AML at a single center from 2007 to 2023 and annotated clinicopathologic characteristics and outcomes. Results: We identified 492 (21%) with AML and MF. We found 344 (69.9%) had MF 0-1 and 148 (30.1%) had MF 2-3. Median age was 67 (IQR: 57-73). Fifty-five (11.1%) had a history of myeloproliferative neoplasm (MPN). Patients with MF 2-3 were associated with complex cytogenetics (39.2%), JAK2 mutations (25.7%), and lower incidence of IDH2 (16.9%) or CEBPA (15.5%) mutations (Table). For patients with MF 0-1, median overall survival (mOS) was 14.2 months compared to 7.5 months for those with MF 2-3 (p<0.005). Survival in patients with MPN history was 9.4 months compared to 12.4 months in patients with de novo AML. In a multivariate analysis, MF 2-3 (HR 2.00 95%CI 1.59-2.51), non-diploid cytogenetics (HR 1.29, 95%CI 1.33-1.69), and number of co-morbidities (HR 1.26 95%CI 1.10-1.43) were prognostic for shorter mOS. Sixty-four percent were treated with low-intensity chemotherapy (LIC), 36.1% with intensive chemotherapy (IC). Complete remission (CR)/CR with incomplete count recovery (CRi) rates were 63.5% for IC vs 37.9% for LIC (p=0.007). Four-week mortality after induction was 5.8% with IC, 8.4% with LIC (p = 0.809). In patients aged 60 and older, with MF 2-3, intensive therapy did not result in improved survival (6.5 months vs 7.0 months, p = 0.19). Conclusions: Patients with AML and MF 2-3 have worse outcomes irrespective of MPN history. For patients aged 60 and above, intensive chemotherapy does not result in improved survival. Patient characteristics by degree of marrow fibrosis mild (0-1), advanced (2-3). No. (%) / median [IQR] Overall (n=492) MF 0-1 (n=344) MF 2-3 (n=148) p Female, n (%) 224 (45.5) 162 (47.1) 62 (41.9) 0.335 Age 67.0 [57.0, 73.0] 67.0 [57.0,74.0] 66.0 [56.8,72.0] 0.508 ANC x10 9 /L 0.7 [0.2, 2.0] 0.6 [0.2,1.7] 1.1 [0.4,3.0] <0.001 Hemoglobin g/dL 9.2 [8.6, 9.7] 9.3 [8.6,9.8] 9.1 [8.5,9.6] 0.07 Platelet count x10 3 /L 34.0 [19.0, 71.5] 37.0 [20.0,69.0] 31.0 [17.0,75.5] 0.289 Bone marrow blast % 41.0 [24.0, 65.0] 47.0 [26.0,69.0] 30.0 [22.0,52.5] <0.001 Diploid CG 143 (29.1) 109 (31.7) 34 (23.0) 0.065 Complex CG 143 (29.1) 85 (24.7) 58 (39.2) 0.002 History of MPN 145 (29.5) 90 (26.2) 55 (37.2) 0.019 TET2 194 (39.4) 141 (41.0) 53 (35.8) 0.328 JAK2 100 (20.3) 62 (18.0) 38 (25.7) 0.07 RAS 130 (26.4) 93 (27.0) 37 (25.0) 0.72 CEBPA 118 (24.0) 95 (27.6) 23 (15.5) 0.006 IDH2 114 (23.2) 89 (25.9) 25 (16.9) 0.04 OS (months), median 11.3 14.2 7.5 <0.001 OS: overall survival.