Mortality and relapse dynamics in AML after three years of complete remission.

Patients with AML remain at risk of death after therapy. Our objective was to characterize patients with AML after three years in remission. 453 patients were documented to be alive and in remission 3 years after diagnosis, median follow-up was 7.

Outcomes of patients with newly diagnosed acute myeloid leukemia with FLT3-tyrosine kinase domain mutations: Prognostic implications of NPM1 co-mutation.

Background: The prognostic impact of Fms-like tyrosine kinase 3 (FLT3)-tyrosine kinase domain (TKD) mutation in patients with acute myeloid leukemia (AML) is not well defined. The authors described outcomes of one of the largest cohorts of patients with FLT3-TKD mutated (FLT3-TKD) AML to date.

Methods: This retrospective study included patients with newly diagnosed AML who received frontline treatment at The University of Texas MD Anderson Cancer Center from January 2012 to March 2024 divided into two cohorts: FLT3-TKD AML and nucleophosmin-mutated (NPM1)/FLT3-TKD wild-type (FLT3-TKD) AML.

Contemporary outcomes of octa-nonagenarians with newly diagnosed acute myeloid leukemia.

Background: Octa-nonagenarians with acute myeloid leukemia (AML) represent a high-risk group due to frequently poor performance status, adverse genomics (e.g., TP53 mutations, complex karyotype), a high incidence of secondary AML, and inability to undergo an allogeneic stem cell transplantation.

Current Treatment Strategies for FLT3-Mutated Acute Myeloid Leukemia in Patients not Candidates for Intensive Chemotherapy.

Purpose Of Review: Younger patients with acute myeloblastic leukemia with FLT3 mutations (FLT3-mutated AML) benefit from the addition of FLT3 inhibitors to intensive chemotherapy. However, patients who are not eligible for intensive chemotherapy have poor outcomes with standard low-intensity treatments. In this review we assess the current state of treatment strategies for patients with FLT3-mutated AML who are not candidates for intensive chemotherapy.

Erythroid-predominant myelodysplastic neoplasms exhibit a distinct genomic landscape with poor outcomes after venetoclax-based therapy.

Erythroid differentiation confers BCL-XL dependence and venetoclax resistance in acute myeloid leukemia (AML). However, whether myelodysplastic neoplasms (MDS) with erythroid predominance (EP), defined by ≥50% erythroid bone marrow elements, have distinct biology and drug sensitivities remains unknown. To study this, we evaluated an MDS patient cohort (n = 371) and showed that EP MDS (n = 67, 18%) are characterized by higher TP53 (multihit TP53: 36% vs 17%, p = 0.

Landscape and clinicopathologic features of RAS pathway mutations in chronic myelomonocytic leukemia.

RAS pathway mutations (RASMT) induce proliferative features and promote transformation in chronic myelomonocytic leukemia (CMML). However, the unique clonal landscape and hierarchy of distinct RASMT remain unexplored. To characterize the landscape, architecture and implications of unique RASMT in CMML we evaluated a cohort of 814 patients with CMML.

Multimodal and Data-Driven Assessment of Myeloid Neoplasms Refines Classification across Disease States.

Unlabelled: The World Health Organization fifth edition and International Consensus Classification for myeloid neoplasms both incorporate empirical numerical thresholds to morphologic and molecular features defining certain disease entities. However, the clinical implications of these thresholds remain unclear. We analyzed a large cohort (N = 6,976) of patients with myeloid neoplasms to evaluate the impact of proposed yet different numerical thresholds for variant allele frequency of genetic mutations or hematologic parameters set forth by the World Health Organization fifth edition and International Consensus Classification for classification of SF3B1-mutated myelodysplastic neoplasms, NPM1-mutated acute myeloid leukemia (AML), and oligomonocytic chronic myelomonocytic leukemia.

Clonal evolution of hematopoietic stem cells after autologous stem cell transplantation.

The impact of exogenous stressors, such as cancer chemotherapies, on the genomic integrity and clonal dynamics of normal hematopoiesis is not well defined. We conducted whole-genome sequencing on 1,276 single-cell-derived hematopoietic stem and progenitor cell (HSPC) colonies from ten patients with multiple myeloma treated with chemotherapies and six normal donors. Melphalan treatment significantly increased the mutational burden, producing a distinctive mutation signature, whereas other chemotherapeutic agents had minimal effects.

Outcomes of Frontline Triplet Regimens With a Hypomethylating Agent, Venetoclax, and Isocitrate Dehydrogenase Inhibitor for Intensive Chemotherapy-Ineligible Patients With Isocitrate Dehydrogenase-Mutated AML.

Purpose: The development of targeted therapeutics has revolutionized treatment for elderly patients with AML. Two doublet regimens are approved in the frontline setting for intensive chemotherapy (IC)-ineligible AML: venetoclax (VEN) in combination with hypomethylating agent (HMA) therapy and azacitidine (AZA) plus ivosidenib (IVO) specifically for -mutated AML. Although both regimens have improved AML outcomes, most patients will either not respond to frontline therapy or relapse, with dismal salvage outcomes.

Bexmarilimab plus azacitidine for high-risk myelodysplastic syndrome and relapsed or refractory acute myeloid leukaemia: results from the dose-escalation part of a multicentre, single-arm, phase 1/2 trial.

Background: Bexmarilimab blocks Clever-1 on macrophages to enhance antigen presentation and T cell activation. Because Clever-1 is expressed by myeloid leukaemia cells, bexmarilimab may combat leukaemia and influence the tumour microenvironment to augment the effectiveness of standard-of-care therapy in patients with myelodysplastic syndrome and acute myeloid leukaemia. The aim of this study was to determine the safety of bexmarilimab in combination with standard-of-care treatment in myelodysplastic syndrome and acute myeloid leukaemia and to identify the recommended dose for expansion of bexmarilimab in combination with standard of care.

A Phase 2 Trial of CPX-351 Combined With Venetoclax in Relapsed or Refractory Acute Myeloid Leukemia.

Outcomes in patients with relapsed/refractory (RR) AML are poor. We sought to investigate if CPX-531 in combination with venetoclax (CPX + VEN) was tolerable and effective in RR AML. This was a single institution phase 1b/2 trial of CPX + VEN.

Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Acute Myeloid Leukaemia.

Introduction: This phase 2 study evaluated magrolimab+venetoclax (VEN)+azacitidine (AZA) in untreated, unfit acute myeloid leukaemia (AML) and magrolimab+mitoxantrone+etoposide+cytarabine in relapsed/refractory (R/R) AML.

Methods: Endpoints included complete remission rate (CRR), overall response rate (ORR), overall survival (OS) and safety.

Results: Eighteen and 36 patients were enrolled into the unfit and R/R AML arms, respectively.

Characteristics and outcomes of newly diagnosed acute myeloid Leukemia with KMT2A rearrangements.

Acute myeloid leukemia (AML) with KMT2A rearrangement (KMT2Ar) has poor outcomes. We analyzed 1,611 patients with AML and 4.3% demonstrated rearrangements in KMT2A.

BLAST: a globally applicable and molecularly versatile survival model for chronic myelomonocytic leukemia.

We sought to develop a survival model in chronic myelomonocytic leukemia (CMML) that is primarily based on clinical variables and examine additional impact from mutations and karyotype. A total of 457 molecularly annotated patients were considered. Multivariable analysis identified circulating blasts ≥2% (1 point), leukocytes ≥13 × 109/L (1 point), and severe (2 points) or moderate (1 point) anemia as preferred risk variables in developing a clinical risk stratification tool for overall survival (OS), acronymized to "BLAST": low risk (0 points; median, 63 months); intermediate risk (1 point; median, 28 months; hazard ratio [HR], 2.

Synergistic Activity of Combined FLT3-ITD and MDM2 Inhibition with Quizartinib and Milademetan in FLT3-ITD Mutant/TP53 Wild-type Acute Myeloid Leukemias.

Purpose: Acute myeloid leukemia (AML) is characterized by frequent mutations in FMS-like tyrosine kinase 3 (FLT3), overexpression of murine double minute 2 (MDM2), and TP53 wild-type (WT). Monotherapies targeting FLT3 frequently result in the development of resistant disease. In this study, we investigated the antileukemic efficacy of co-targeting FLT3 and MDM2 with quizartinib and milademetan (Q/M) in FLT3 internal tandem duplication (FLT3-ITD) AML cell lines, xenograft and patient-derived xenograft (PDX) models, and a phase I clinical trial.

Safety and efficacy of the combination of azacitidine with venetoclax after hypomethylating agent failure in higher-risk myelodysplastic syndrome.

Objective: Therapies for patients with higher-risk myelodysplastic syndromes (HR-MDS) who have failed hypomethylating agents (HMAs) are needed. This Phase I/II study evaluates the safety, tolerability, and efficacy of venetoclax, an orally bioavailable BCL-2 inhibitor, in combination with azacitidine in this population.

Methods: We conducted a single-center, dose-escalation, Phase I/II trial (NCT04550442) involving 33 patients with HR-MDS or CMML (IPSS ≥ 1.