Use of Venetoclax in Patients with Relapsed or Refractory Acute Myeloid Leukemia: The Pethema Registry Experience (2020)

Introduction The prognosis of patients with recurrent or refractory acute myeloid leukemia (AML-RR) is very poor, especially if they are not candidates for allogeneic transplantation (allo-SCT) after a second complete response (CR). Venetoclax, a potent and selective inhibitor of the antiapoptotic protein BCL-2, was approved by the FDA in combination with hypomethylating agents (HMAs) or low-dose cytarabine (LDAC) in patients with newly diagnosed AML of age ≥ 75 years, or who have comorbidities that preclude the use of intensive chemotherapy. However, the evidence in AML-RR patients is still scarce. For this reason, the objective of our study is to retrospectively analyze the efficacy of the off-label use of venetoclax in patients with AML-RR. Methods We conducted a retrospective, multicenter, observational study of a cohort of patients with AML-RR who were treated with venetoclax in the hospitals of the PETHEMA group. We evaluated efficacy, CR/CRi rate and overall survival (OS). We performed a descriptive analysis. Overall survival (OS) was calculated using the Kaplan-Meier method. Results A total of 41 patients were included, 25 men and 16 women, with a median age of 68 years (25 - 82 years) and an ECOG ≥ 2 at the beginning of the venetoclax treatment in 52% of the cases. Seventy-five percent of patients had AML with myelodysplasia-related changes. 25 patients (61%) were at high risk according to the European Leukemia Net 2017. Sixty-six percent of patients received ≥2 previous lines (range, 1-4), 29 patients (71%) received intensive first line chemotherapy, 10 (25%) received a previous transplant and 18 (44%) received previous treatment with HMA. Venetoclax median treatment duration was 40 days, and it was administered in 54% with azacitidine, 34% with decitabine and 12% with LDAC. In all, 11% of patients achieved CR/CRi. Only 10% of patients received subsequent salvage treatment. With a median follow-up time of 166 days (range, 21 - 311), 65% of the patients died. The median OS from diagnosis was 15 months (1 - 67 months) and the median from venetoclax initiation was 78 days (2 - 311 days). Those patients who achieved CR/CRi had higher OS (median not reached vs. 78 days, p= 0.048). Regarding toxicity, it was the expected in these patients. Twenty-eight percent of the patients required discontinuation of treatment due to toxicity. Sixty percent of the patients were admitted at some time during treatment with venetoclax, mainly because of infections (53%), 12% because of bleeding and other causes in 15%. Conclusions Our real-life series depicts a marginal probability of CR/CRi and poor OS after venetoclax-based salvage. Patients treated with this regimen had very poor-risk features, and were heavily pre-treated, which could explain in part the observed poor outcomes. Although follow-up is still short, the small proportion of responders did not reach the median overall survival. Further studies will help to identify those patients potentially benefiting from venetoclax-based salvage regimens. Disclosures Sanchez: Amgem: Other: travel grants; Janssen: Other: travel grants; Roche: Other: travel grants; Abbvie: Other: travel grants; Celgene: Other: travel grants. Tormo:Roche: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; MSD: Honoraria; Daiichi Sankyo: Honoraria. OffLabel Disclosure: The objective of our study is to retrospectively analyze the efficacy of the off-label use of venetoclax in patients with recurrent or refractory acute myeloid leukemia