Abstract
The potent oral inhibitor of BCL2, venetoclax (VEN), used to treat adults with chronic lymphocytic leukaemia, has been approved in US for the treatment of naïve patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy and recently in Europe, too. However, the drug has been used for years in combination with hypomethylating agents (HMAs) in patients not eligible to other treatment option, according to the so-called off-label use. We collected real-world data about patients treated with VEN + HMAs in the context of a pharmacovigilance project focused on the evaluation of the safety and effectiveness of drugs used for unapproved indication in Italian hospitals. From March to December 2020, 24 patients started treatment with VEN combined with HMAs. 21 patients have been assessed for response. Eleven (52%) patients reached complete remission (CR), and three patients (14%) CR with partial hematological recovery (CRh), with a median duration of response of 4.5 months (range 0.5–12.5). 19 patients experienced at least 1 adverse drug reaction (ADR), mostly serious, including 3 deaths (9% of ADRs; 12.5% of patients) in febrile neutropenia. Hematological toxicities and infections (cytopenia, neutropenia, febrile neutropenia, sepsis), were the most reported ADRs (84.4%). In general, neutropenic fever occurred more frequently in patients treated with decitabine (7 out of 9, 78%) compared to azacitidine (5 out of 15, 33%; p = 0.03), whereas response assessment did not differ based on used HMA (p = 0.1). These results confirm the benefit-risk profile of VEN in a real-world setting of patients with no adequate therapeutic options.
Highlights
Venetoclax (VEN) is a potent oral inhibitor of the antiapoptotic molecule BCL2, used to treat adults with chronic lymphocytic leukaemia (CLL), in association with obinutuzumab in patients who have not previously been treated or with rituximab in patients who have received at least one previous treatment.It is used as monotherapy in patients with 17p deletion or TP53 mutation who cannot be treated with or have failed a B-cell receptor pathway inhibitor or in the absence of these genetic changes in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.this drug has demonstrated activity and a good safety profile in patients with other hematological diseases, in particular acute myeloid leukemia (AML)
This prospective pharmacovigilance sub-study started on March 2020 at the University Hospital of Catania and enrolled AML patients, who met the eligibility criteria defined by the L.648/96, i.e., adult patients with newly diagnosed AML not eligible for intensive induction chemotherapy or aged 75 or more, were treated with hypomethylating agents (HMAs) combined with venetoclax
Treatment with venetoclax has been temporally interrupted after cycle 1 in 4 patients out of 21 (19%), in order to let the hematological recovery, two of them reaching the CR with partial hematological recovery (CRh), 1 in partial response (PR) and 1 with persistence of disease
Summary
Venetoclax (VEN) is a potent oral inhibitor of the antiapoptotic molecule BCL2, used to treat adults with chronic lymphocytic leukaemia (CLL), in association with obinutuzumab in patients who have not previously been treated or with rituximab in patients who have received at least one previous treatment.It is used as monotherapy in patients with 17p deletion or TP53 mutation who cannot be treated with or have failed a B-cell receptor pathway inhibitor or in the absence of these genetic changes in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.this drug has demonstrated activity and a good safety profile in patients with other hematological diseases, in particular acute myeloid leukemia (AML). Venetoclax (VEN) is a potent oral inhibitor of the antiapoptotic molecule BCL2, used to treat adults with chronic lymphocytic leukaemia (CLL), in association with obinutuzumab in patients who have not previously been treated or with rituximab in patients who have received at least one previous treatment It is used as monotherapy in patients with 17p deletion or TP53 mutation who cannot be treated with or have failed a B-cell receptor pathway inhibitor or in the absence of these genetic changes in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor. This fact highlights the high unmet medical need for more effective and well-tolerated treatment options in this population, at least in part covered by the use of venetoclax
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