Combination Strategies with Menin Inhibitors for Acute Leukemia.

Menin inhibitors are targeted therapies for the treatment of genetically defined subsets of acute leukemia. The menin inhibitor revumenib is currently approved for relapsed or refractory leukemia with rearrangement of lysine methyltransferase 2 A (KMT2A). However, multiple other menin inhibitors are currently in clinical development aimed at targeting additional subsets such as nucleophosmin 1 (NPM1) mutations which form up to 30% of acute myeloid leukemia.

Management of Chronic Myeloid Leukemia During Pregnancy: Review of Evidence and Treatment Algorithm.

Philadelphia chromosome-positive chronic myeloid leukemia (CML) during pregnancy is rare, with an annual incidence of 1 per 100,000 pregnancies. Managing CML in pregnancy is challenging due to concerns about the teratogenicity of the BCR::ABL1 tyrosine kinase inhibitors (TKIs). While some pregnant patients with chronic-phase CML may be managed with close monitoring and no therapy, others, particularly those diagnosed in the first trimester, may require treatment to prevent disease progression and maternal complications.

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 and patterns of relapse with ponatinib-based therapy in patients with chronic myeloid leukemia in myeloid blast phase.

We analyzed 76 patients who received a ponatinib-based regimen, either as monotherapy or in combination with chemotherapy, for chronic myeloid leukemia in myeloid blast phase (CML-MBP). The rate of morphological remission with or without count recovery (i.e.

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.

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.

Management of chronic myeloid leukemia in 2025.

Chronic myeloid leukemia (CML) has an annual incidence of approximately two cases per 100,000. The reduction in annual mortality from 10%-20% to 1% with BCR::ABL1 tyrosine kinase inhibitors (TKIs) has resulted in an increased prevalence in the United States of an estimated 150,000 cases in 2025. This translates into a worldwide estimated prevalence of approximately 5 million cases, and hence the need to make TKIs available and affordable to all patients.

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.

Risk of early death after acute leukemia diagnosis among adolescents and young adults.

Background: Advances in care have led to improvements in survival for adolescents and young adults (AYAs) diagnosed with cancer; however, the risk of early death remains high for certain cancers, particularly acute leukemias. Risk factors for early death in AYAs diagnosed with acute leukemia have not been well studied.

Methods: The Surveillance, Epidemiology, and End Results registry was used to assess risk of early death (within 2 months of diagnosis) in AYAs diagnosed with acute leukemia (n = 16 153).

Lower-intensity chemo-immunotherapy with cladribine, low-dose cytarabine, venetoclax and blinatumomab produces high response rates in patients with -negative B-cell / myeloid mixed phenotype acute leukemia.

Not available.

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.

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.

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.

Unusually Indolent CML: Absence of Complete Cytogenetic Response after 10 Years of Tyrosine Kinase Inhibitor Therapy.

Background: With BCR::ABL1 tyrosine kinase inhibitor (TKI) therapy, most patients with chronic-phase chronic myeloid leukemia (CML-CP) can achieve complete cytogenetic response (CCyR) within 6 months of therapy. However, no studies have investigated patients who do not achieve CCyR yet maintains stable disease on long-term TKI treatment. Here we investigated 30 CML-CP patients who did not achieve CCyR but remained free of blastic progression for at least 10-year while on TKI therapy.

Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study.

The prognosis for relapsed or refractory (R/R) nucleophosmin 1-mutated (NPM1m) acute myeloid leukemia (AML) is poor and represents an urgent unmet medical need. Revumenib, a potent, selective menin inhibitor, was recently approved for the treatment of R/R acute leukemia with a KMT2A translocation in patients aged ≥1 year based on results from the phase 1/2 AUGMENT-101 study. Here, we present results from patients with R/R NPM1m AML enrolled in the phase 2 portion of AUGMENT-101.

Somatic TP53 Mutations Drive T and NK Cell Dysfunction in AML and Can be Rescued by Reactivating Wild Type p53.

Therapeutic advances in immunotherapy have significantly improved outcomes in lymphomas and myelomas, yet patients with TP53-mutant acute myeloid leukemia (AML) continue to be challenged. While TP53 mutations in leukemic blasts have been extensively characterized, their incidence and impact within immune cells remain largely unexplored. Here, using single-cell multi-omics and integrated phenotypic analyses, we identify TP53 mutations in T and NK cells from AML patients.

Azacitidine, Venetoclax, and Magrolimab in Newly Diagnosed and Relapsed Refractory Acute Myeloid Leukemia: Phase Ib/II Study and Correlative Analysis.

Purpose: Magrolimab is a monoclonal antibody directed against the macrophage checkpoint CD47 on myeloid leukemia cells that was preclinically synergistic with azacitidine-venetoclax, warranting further clinical evaluation.

Patients And Methods: In this phase Ib/II study, the triplet combination of azacitidine, venetoclax, and magrolimab was evaluated in adult patients with first-line (ineligible for intensive chemotherapy) and relapsed/refractory acute myeloid leukemia. Azacitidine was dosed at 75 mg/m2 for 7 days, venetoclax at 400 mg/day for 28 days, and magrolimab (recommended phase II dose) as follows: 1 mg/kg dose on days 1 and 4, 15 mg/kg on day 8, and 30 mg/kg on days 11, 15, and 22 (cycle 1), followed by 30 mg/kg weekly for cycle 2 and then 30 mg/kg every 2 weeks for cycle 3 and beyond.