The effectiveness of venetoclax (VEN) in relapsed or refractory acute myeloid leukemia (RR-AML) has not been well established. This retrospective, multicenter, observational database studied the effectiveness of VEN in a cohort of 51 RR-AML patients and evaluated for predictors of response and overall survival (OS). The median age was 68 years, most were at high risk, 61% received ≥2 therapies for AML, 49% had received hypomethylating agents, and ECOG was ≥2 in 52%. Complete remission (CR) rate, including CR with incomplete hematological recovery (CRi), was 12.4%. Additionally, 10.4% experienced partial response (PR). The CR/CRi was higher in combination with azacitidine (AZA; 17.9%) than with decitabine (DEC; 6.7%) and low-dose cytarabine (LDAC; 0%). Mutated NPM1 was associated with increased CR/CRi. Median OS was 104 days (95% CI: 56–151). For the combination with AZA, DEC, and LDAC, median OS was 120 days, 104 days, and 69 days, respectively; p = 0.875. Treatment response and ECOG 0 influenced OS in a multivariate model. A total of 28% of patients required interruption of VEN because of toxicity. Our real-life series describes a marginal probability of CR/CRi and poor OS after VEN-based salvage. Patients included had very poor-risk features and were heavily pretreated. The small percentage of responders did not reach the median OS.

In adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) genetic risk is usually combined with measurable residual disease (MRD) assignment to consolidation therapy. However, this combination is not uniform across trials and centralized assessment is not always performed. This study analyzed patients' outcomes using centrally assessed MRD and genetics. Patients with high genetic risk (HGR), those who required two induction cycles for complete remission (CR), and CR patients with end-of-induction (EOI) MRD ≥0.01% were assigned to allogeneic hematopoietic stem cell transplant (alloHSCT), while the remaining patients were assigned to delayed consolidation and maintenance. HGR for B-ALL included KMT2A rearrangements, low hypodiploidy and age >35 years, homozygous TP53 mutations/deletions, or concomitant IKZF1 and CDKN2A/B deletions. HGR in T-ALL included absence of NOTCH1/FBXW7 mutations and/or K/NRAS or PTEN alterations. Patients with early T-ALL (ETP) received a different induction regimen, and all were assigned to alloHSCT. Median (range) age of 436 patients was 39 (18-60) years, 332 with B-lineage ALL and 104 T-ALL. By intention to treat, 243 non-ETP patients (61%) were assigned to alloHSCT and 157 (39%) to CT. The 3-year overall survival (OS) probability (95% CI) was 64% (58%-69%). For patients with CR and EOI MRD<0.01% without HGR (n=109), the OS probability was 81% (70%-89%), compared with 50% (34%-63%) for MRD-negative patients with HGR (n=64). In patients with ETP-ALL the probability of 3-year OS was 61% (37%-79%). The combination of genetics and MRD allows accurate identification of adult Ph- ALL patients candidates to alloHSCT or chemotherapy. The trial was registered at www.ClinicalTrials.gov: NCT04179929