First Report of Clinical Response to Venetoclax in Early T-Cell Precursor Acute Lymphoblastic Leukemia

Venetoclax in association with decitabine as effective bridge to transplant in a case of relapsed early T‐cell lymphoblastic leukemia

“…Despite the role demonstrated in lymphoproliferative disease such as CLL and MCL, the employment of venetoclax in ALL is reported in only three published cases. 8,10 Maturation stage of T-ALL cells determines BCL-2 vs BCL-XL dependence and sensitivity to BCL-2 inhibition. 12 Venetoclax use is supported by in vitro studies on T-ALL-derived cell lines and ex vivo patients derived blasts, suggesting a rationale for a novel therapeutic strategy.…”

“…Initial early T-ALL phenotype was confirmed by flow cytometry. According to promising preclinical data and pivotal case reports about venetoclax efficacy in T-ALL, 7,8,10 we decided to test BCL-2 expression on the leukemic blasts, and we found a high expression ( Figure 1). This finding encouraged us to start salvage treatment with standard-dose decitabine, 20 mg/m 2 for 5 days every 28 days in combination with venetoclax, daily dose 400mg, after a brief rump up of 6 days (initial daily dose 100 mg).…”

“…7 Clinical response to venetoclax was recently reported in 2 early T-cell precursor relapsed/refractory ALL patients. 8 Furthermore, hypomethylating agents demonstrated a potential role in ALL treatment, suggesting a rationale for combination strategies. 9 According to this background, venetoclax in combination with decitabine was successfully used to treat a patient who experienced T-ALL relapse after allo-SCT.…”

Failure of tofacitinib to achieve an objective response in a DDX3X-MLLT10 T-lymphoblastic leukemia with activating JAK3 mutations

“…Preclinical studies have shown in vitro and in vivo sensitivity of some T-ALL cell lines to venetoclax, either alone or in combination with other agents (Peirs et al 2014). A report of venetoclax combined with low-intensity chemotherapy reported a durable response in one patient with early T-cell precursor ALL, and a complete but transient response in one patient with T-ALL (Numan et al 2018). This was consistent with preclinical data demonstrating particular susceptibility of ETP-ALL to BCL2 inhibition, because of lesser dependence on BCL-XL compared to more mature subtypes of T-ALL (Chonghaile et al 2014).…”

Targeted therapy paves the way for the cure of acute lymphoblastic leukaemia

“…Recent insights into the biology of ETP‐ALL have revealed BCL2 dependence and hence sensitivity to BCL2 antagonism. A report of a patient with refractory ETP‐ALL and another with T‐ALL and some features suggestive of the ETP subtype showed excellent responses to venetoclax given in combination with cytotoxic chemotherapy, suggesting the promise of this medication in the treatment of ETP‐ALL (Numan et al , ).…”