Venetoclax in Relapsed/Refractory Acute Myeloid Leukemia: Are Supporting Evidences Enough?

Abstract

Despite the progress in the development of new therapeutic strategies, relapsed/refractory (R/R) acute myeloid leukemia (AML) still represents a high unmet medical need. Treatment options in this setting include enrollment into clinical trials, allogeneic stem cell transplantation and/or targeted therapy. Nevertheless, it is associated with poor outcomes. Thus, the development of new treatments, which could ameliorate the prognosis of these patients with a good safety profile are highly demanded. Recently, venetoclax (VEN) has been approved for naïve AML patients unfit for intensive chemotherapy. In this regard, regimens including VEN could represent a valuable treatment option even in those with R/R disease and several studies have been conducted to demonstrate its role in this clinical setting. This review aims to summarize the current evidence on the use of VEN regimens in the treatment of R/R AML.

Clinical efficacy of azacytidine and venetoclax and prognostic impact of Tim-3 and galectin-9 in acute myeloid leukemia and high-risk myelodysplastic syndromes: A single-center real-life experience

“…Our CR and CCR rates in the historical cohort were higher than those reported, likely because only 45% and 32% of AML patients in the historical cohort survived to the fourth and eight cycle, respectively, and were those subjects with robust response to therapy. Our results were similar to those reported in other real-world studies including AML patients treated with azacytidine plus venetoclax ( Brancati S et al, 2021 ; Gozzo L et al, 2021 ). Indeed, in previously published AML case series (N = 21), a CR rate of 52% and a CCR of 67% has been reported, with a median duration of response of 4.5 months (range, 0.5–12.5 months).…”

Survival outcomes in patients with acute myeloid leukaemia who received subsequent therapy for relapse in QUAZAR AML‐001

“…Notably, new targeted agents for R/R AML, such as gilteritinib and isocitrate dehydrogenase (IDH) inhibitors (indicated in patients with FLT3 mut AML and IDH1 mut / IDH2 mut AML, respectively), are now available 22,23 . Venetoclax‐based combinations, although only approved in the front‐line setting for patients ineligible for IC, have also shown efficacy in the R/R AML setting and are often used in patients following relapse after IC 29–31 . The efficacy of Oral‐AZA maintenance after initial treatment with a venetoclax‐based low‐intensity induction strategy has not been established, but is the subject of debate as clinicians navigate potential post‐remission therapy options for patients with AML in whom allogeneic HSCT is not intended.…”

“…22,23 Venetoclax-based combinations, although only approved in the front-line setting for patients ineligible for IC, have also shown efficacy in the R/R AML setting and are often used in patients following relapse IC. [29][30][31] The efficacy of Oral-AZA maintenance after initial treatment with a venetoclax-based low-intensity induction strategy has not been established, but is the subject of debate as clinicians navigate potential post-remission therapy options for patients with AML in whom allogeneic HSCT is not intended. Also of clinical interest is the potential use of Oral-AZA as a bridge to transplant, that is, as a short-term therapy to maintain remission while patients are under consideration for HSCT.…”

Severe Gastrointestinal Toxicity Following the Use of Gilteritinib: A Case Series and Analysis of Postmarketing Surveillance Data

“…FMS-like tyrosine kinase 3 (FLT3) inhibitors represent the new standard of care for patients with FLT3-mutant acute myeloid leukemia (AML), in both the first line and salvage 2 of 12 settings [1][2][3][4][5]. First-generation FLT3 multitargeted tyrosine kinase inhibitors (TKIs), such as midostaurin and sorafenib, are limited by poor drug selectivity, weak potency and unfavorable protein-binding characteristics [6].…”