Venetoclax plus azacitidine as genetic-driven bridge-to-transplant therapy for IDH2-mutated acute myeloid leukaemia (AML) refractory to intensive chemotherapy. Proof-of-concept case reports

Despite the greater biological understanding and the new drugs available, acute myeloid leukaemia (AML) patients who are refractory to intensive induction chemotherapy represents an unmet clinical need, especially in young/fit adults who are eligible for bone marrow transplantation. Since venetoclax/azacitidine (ven/aza) was introduced in AML management in 2020, survival of elderly/unfit patients has dramatically improved, especially in those carrying NPM1 or IDH2 mutations. However, the use of ven/aza in young and fit adults remains limited, raising ongoing debate about its potential role beyond patients ineligible to intensive chemotherapy. Here, we discuss three under 60 years chemorefractory AML patients, who, given the concomitant IDH2 mutations, were started to ven/aza as bridge-to-transplant and successfully treated. These cases confirm the extraordinary sensitivity of IDH2-mutated AML to aza/ven even in the refractoriness setting and show that such less-intensive regimen can be driven by genetics offering a promising alternative to intensive salvage chemotherapy, while preserving patient fitness for allo-transplant.