AML-013: Venetoclax in Patients with Relapsed or Refractory Acute Myeloid Leukemia – A Retrospective Study of a Real-World Setting

Context In November 2018, the FDA approved the use of venetoclax combined with hypomethylating agents (HMA) or low-dose cytarabine (LDAC) in patients with newly diagnosed acute myeloid leukemia (AML) of age ≥ 75 years, or with comorbidities that preclude the use of intensive chemotherapy. However, the evidence in relapse/ refractory (R/R-AML) patients is scarce. Objective To analyze the efficacy and safety of the off-label use of venetoclax in patients with R/R-AML. Design Retrospective, multicenter, observational study in 5 hospitals from Castilla y León region, Spain. Interventions All data were collected from patients' medical records and included: concomitant diseases, main baseline characteristics, prior treatment and the response obtained, startend date of venetoclax, dose and combination. Main outcome measures rates of CR/CRi (complete remission/complete remission with incomplete hematologic response, overall survival (OS), hematological toxicity, mortality. Results We included 10 patients (8 men/ 2 women), median age 73.5 (41-78) years, and ECOG <2 at diagnosis. 55.5% belonged to the high-risk prognostic group according to European LeukemiaNet 2017. 55.5% received intensive first-line chemotherapy and 60% received ≥2 (1-3) previous lines. 2 patients received a previous transplant, and 6 received previous treatment with HMA. Prior to venetoclax, 50% of patients had ECOG ≥2. Median venetoclax treatment duration was 27 (0 – 62) days. Venetoclax was administered with azacitidine (75 mg/m2 – 7d) in 60% of patients, with decitabine (20 mg/m2 - 5d) in 30% and with LDAC (20 mg/m2- 10d) in 10%. Only 10% of patients achieved CR/CRi. Of the remaining, only 20% received subsequent salvage therapy. Within a median follow-up time of 39 (2-147) days, 70% of the patients died. Median OS from diagnosis was 15 months (95% CI 9.7 – 20.3) and from the start of venetoclax was 49 days (95% CI: 31.8 – 66.2). One patient discontinued treatment due to hematological toxicity. Conclusions In the R/R-AML setting, the rate of CR/CRi and OS of venetoclax combination treatment is low. However, the patients included had very poor prognosis. These results show a real-world evolution of patients without being included in clinical trials under strict inclusion criteria that diminish the selection of patients. Further research is warranted. In November 2018, the FDA approved the use of venetoclax combined with hypomethylating agents (HMA) or low-dose cytarabine (LDAC) in patients with newly diagnosed acute myeloid leukemia (AML) of age ≥ 75 years, or with comorbidities that preclude the use of intensive chemotherapy. However, the evidence in relapse/ refractory (R/R-AML) patients is scarce. To analyze the efficacy and safety of the off-label use of venetoclax in patients with R/R-AML. Retrospective, multicenter, observational study in 5 hospitals from Castilla y León region, Spain. All data were collected from patients' medical records and included: concomitant diseases, main baseline characteristics, prior treatment and the response obtained, startend date of venetoclax, dose and combination. rates of CR/CRi (complete remission/complete remission with incomplete hematologic response, overall survival (OS), hematological toxicity, mortality. We included 10 patients (8 men/ 2 women), median age 73.5 (41-78) years, and ECOG <2 at diagnosis. 55.5% belonged to the high-risk prognostic group according to European LeukemiaNet 2017. 55.5% received intensive first-line chemotherapy and 60% received ≥2 (1-3) previous lines. 2 patients received a previous transplant, and 6 received previous treatment with HMA. Prior to venetoclax, 50% of patients had ECOG ≥2. Median venetoclax treatment duration was 27 (0 – 62) days. Venetoclax was administered with azacitidine (75 mg/m2 – 7d) in 60% of patients, with decitabine (20 mg/m2 - 5d) in 30% and with LDAC (20 mg/m2- 10d) in 10%. Only 10% of patients achieved CR/CRi. Of the remaining, only 20% received subsequent salvage therapy. Within a median follow-up time of 39 (2-147) days, 70% of the patients died. Median OS from diagnosis was 15 months (95% CI 9.7 – 20.3) and from the start of venetoclax was 49 days (95% CI: 31.8 – 66.2). One patient discontinued treatment due to hematological toxicity. In the R/R-AML setting, the rate of CR/CRi and OS of venetoclax combination treatment is low. However, the patients included had very poor prognosis. These results show a real-world evolution of patients without being included in clinical trials under strict inclusion criteria that diminish the selection of patients. Further research is warranted.