azacitidine

P2, N=25, Not yet recruiting, First Affiliated Hospital of Zhejiang University

P2/3, N=80, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd.

Induction chemotherapy (cytarabine and idarubicin) initially achieved remission, but subsequent relapses led to the use of venetoclax and 5-azacytidine, which again resulted in remission. This is the first report that molecularly characterizes the HMBOX1::JAK2 fusion in a de novo AML patient. The identification of this novel alteration adds to the growing and heterogeneous molecular landscape of AML and suggests a potential new avenue for targeted therapy.

Despite multiple cycles of azacitidine, within one month, the patient had transitioned into sAML with blasts increased to 55% with heterogeneity in the sample, and TMEM91::TAL1 expression increased to 2.83%...This case illustrates the value of comprehensive molecular profiling, including RNA-seq, in cases of rapidly progressive MDS that cannot be diagnosed through standard molecular diagnostics. The temporal relationship between expression of the fusions and disease progression warrants additional studies of TMEM91::TAL1 in myeloid malignancies.

Although pleural myeloid sarcoma is extremely rare, it must be included in the differential diagnosis for unexplained solid pleural masses, particularly when accompanied by pleural effusion. Upon diagnosis, comprehensive staging investigations, including bone marrow biopsy and flow cytometry, must be performed immediately. The successful management of such complex cases relies on the close collaboration of a multidisciplinary team, including radiologists, pathologists, hematologists, and thoracic surgeons. Radiologists identify atypical imaging features, pathologists confirm the diagnosis through precise immunophenotyping, and ultimately, hematologists formulate and execute the correct treatment plan.

Specifically, MRD negativity after cycle 12 strongly predicted OS (33.9 vs 20.4 months; P=.005) and EFS (33.9 vs 10.1 months; P=.004) with a trend for RFS (32.6 vs 13.5 months; P=.06). TP53 MRD was strongly predictive of outcomes, supporting incorporation of this assay in future novel strategies.

Loss of p53 function is strongly associated with venetoclax resistance, and adding venetoclax to 5-azacitidine provides no overall survival benefit in TP53 -mutant AML. The pro-apoptotic actions of pitavastatin depend on depletion of geranylgeranyl pyrophosphate (GGPP) and can be recapitulated by inhibiting GGPP synthase or geranylgeranyltransferase-1 enzymes. These results provide a mechanistic rationale for adding pitavastatin to AML regimens to prevent or overcome venetoclax resistance.

Platelet-derived growth factor receptor beta (PDGFRB)-rearranged myeloid/lymphoid neoplasms (MLNs) are rare hematologic malignancies typically responsive to tyrosine kinase inhibitors (TKIs) such as imatinib. The patient progressed to acute myeloid leukemia (AML) within 11 months despite sequential therapies including dasatinib and azacitidine-venetoclax, ultimately succumbing to sepsis. This case highlights the limitations of TKI monotherapy in MLNs with PDGFRB rearrangements and co-existing high-risk mutations, underscoring the importance of early molecular profiling and consideration of allogeneic hematopoietic stem cell transplantation in cases with poor risk features.

P=N/A, N=43, Recruiting, The First Affiliated Hospital of Soochow University | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Jul 2025 --> Jul 2026

P2, N=92, Recruiting, The First Affiliated Hospital of Soochow University | Trial completion date: Sep 2025 --> Sep 2026 | Trial primary completion date: Sep 2025 --> Sep 2026

Although the European LeukemiaNet (ELN) classifications (2017, 2022) for AML have been used to stratify outcomes for patients receiving intensive chemotherapy, application to patients receiving less intensive therapy, like azacitidine plus venetoclax, has been less satisfactory. Overall, these data support the importance of molecular sub-classification in defining treatment outcomes to venetoclax-based therapies. NCT02287233; NCT03069352.

P2, N=40, Recruiting, Beijing 302 Hospital