abt-199 and Febrile-Neutropenia

Venetoclax, a selective B cell leukemia/lymphoma-2 (BCL2) inhibitor, has recently shown activity in relapsed or refractory (R/R) acute myeloid leukemia (AML). Effective biomarkers for identifying patients most likely to respond to venetoclax-based treatment are of clinical utility. In this study, we aimed to evaluate the efficacy and safety profiles of venetoclax-based therapy in a total 40 R/R AML patients and identify the potentially predictive factors for response. Overall response rate was 50%, including 9 (22.5%) complete response (CR) or CR with incomplete hematologic recovery of either neutrophil or platelet counts (CRi). Median time to best response was 1.4 months and the median overall survival (OS) was 6.6 months. Presence of intermediate-risk cytogenetics predicted better OS compared to unfavorable-risk cytogenetics. Patients harboring NPM1, RUNX1, or SRSF2 mutations seemed to have higher CR/CRi rates and median OS was significantly longer in RUNX1-mutated patients. On the contrary, patients with FLT3-ITD, TP53, or DNMT3A mutations did not reach any objective response and had worse OS. No laboratory or clinical tumor lysis syndrome was observed and the most common adverse events were prolonged cytopenias which resulted in 67.5% of febrile neutropenia. Patients with concurrent use of azole antifungals had similar incidence of cytopenias compared with those without azole antifungals. In summary, we demonstrate that venetoclax is an effective and well-tolerated salvage option for R/R AML patients. Survival benefits were particularly remarkable in patients with intermediate-risk cytogenetics or RUNX1 mutations. In contrast, TP53, NRAS, and DNMT3A mutations as well as FLT3-ITD conferred negative impact on survival.

Topics: Adult; Aged; Aged, 80 and over; Bridged Bicyclo Compounds, Heterocyclic; Cytogenetics; Disease-Free Survival; Febrile Neutropenia; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mutation; Nucleophosmin; Proto-Oncogene Proteins c-bcl-2; Risk Factors; Sulfonamides; Survival Rate

Topics: Antineoplastic Combined Chemotherapy Protocols; Azacitidine; Bridged Bicyclo Compounds, Heterocyclic; East Asian People; Febrile Neutropenia; Humans; Leukemia, Myeloid, Acute

Venetoclax (Ven) in combination with azacitidine or decitabine (hypomethylating agent; HMA) is the standard-of-care treatment for older (≥75 years) or intensive chemotherapy ineligible adults with newly diagnosed acute myeloid leukemia (AML). Tumor lysis syndrome (TLS) and infectious complications are two of the most concerning associated adverse events. We studied the real-world incidence and outcomes of these adverse events with HMA/Ven in AML patients. Our retrospective analysis included 106 patients (median age 70 years). Of these, 61 (58%) received HMA/Ven in frontline setting while 45 (42%) received in salvage setting. 19 (18%) met laboratory criteria for TLS, five (5%) developed clinical TLS (acute kidney injury). The median time to develop TLS was 2 days (range -2 to 4). During cycle 1, 29 patients (27%) were diagnosed with febrile neutropenia while 26 (25%) developed new infections. Median time to development of new infection was 10 days (1-25). Pneumonia was the most common infection (8%). Febrile neutropenia and/or new infection during cycle 1 was associated with poorer median overall survival compared to those without these complications (4.9 months vs 11.6 months; p = 0.03). In conclusion, incidence of TLS and infections was high in our cohort during initiation of HMA/Ven therapy. This data emphasizes the need for closer monitoring in these patients, especially during the first 7-10 days of treatment, which is often achieved in the inpatient setting.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Azacitidine; Bridged Bicyclo Compounds, Heterocyclic; Decitabine; Febrile Neutropenia; Humans; Leukemia, Myeloid, Acute; Retrospective Studies; Sulfonamides; Tumor Lysis Syndrome

Topics: Allografts; Antineoplastic Combined Chemotherapy Protocols; Azacitidine; Bridged Bicyclo Compounds, Heterocyclic; Combined Modality Therapy; Decitabine; DNA Methylation; Drug Evaluation; Febrile Neutropenia; Germany; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute; Leukocyte Count; Myelodysplastic Syndromes; Recurrence; Retrospective Studies; Salvage Therapy; Sulfonamides; Thrombocytopenia; Transplantation Conditioning; Tumor Lysis Syndrome