Abstract
Introduction: In the Brazilian public health system (SUS), salvage chemotherapy for fit patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) after standard 7+3 induction (7 days of cytarabine plus 3 days of an anthracycline) is usually FLAG-IDA (fludarabine, cytarabine, granulocyte colony-stimulating factor [G-CSF], and idarubicin) or MEC (mitoxantrone, etoposide, and cytarabine). These regimens were associated with significant toxicity and mortality rates of up to 27%. Conversely, for unfit or elderly patients with R/R AML after low-dose cytarabine (LDAC) induction failure, supportive care is typically the only option. Although the venetoclax–cytarabine (VEN-ARAC) or venetoclax–azacitidine (VEN-AZA) combination is approved as first-line therapy for unfit patients, it is generally not available in SUS. The use of these combinations in R/R AML, including younger patients, is emerging.Objective: To determine the complete response rate (CR), time to complete response (TTCR), and overall survival (OS) in patients with R/R AML treated with venetoclax-based salvage therapy after 7+3 induction or LDAC.Methods: We retrospectively analyzed medical records of consecutive patients aged ≥18 years treated at a public hospital in Brazil who received first-line therapy with 7+3 or low-dose cytarabine (LDAC) between May 2022 and May 2025. Patients with R/R AML who subsequently received venetoclax-based (VEN-based) salvage therapy were included. The study was approved by the local ethics committee. CR was defined as <5% bone marrow blasts, TTCR as the interval from initiation of VEN-based therapy to CR, and OS as the time from diagnosis to last follow-up or death. Venetoclax (VEN) was primarily combined with cytarabine or azacitidine, and all patients received dose-adjusted VEN due to concomitant antifungal therapy.Results: Induction with 7+3 and LDAC was administered to 25 and 8 patients, respectively. Eighteen patients developed R/R AML. Among these, the median age was 53 years (range 22.1–82.4); 67% were <60 years, 50% were male, and 89% were self-identified as mixed-race or Black. According to the 2022 ELN risk classification, 61% were intermediate-risk and 22% high-risk; karyotype was unavailable in 11% (2/18), and next-generation sequencing (NGS) was not performed. After 7+3 (n=13) or LDAC (n=4), salvage VEN-based chemotherapy (mostly VEN+ARAC [61%] or VEN+AZA) achieved a CR in 71% (12/17) overall: 69% (9/13) after 7+3 and 75% (3/4) after LDAC, with a median time to CR of 28 days (range 19–149) and 29 days (23–30), respectively. Two patients proceeded to allogeneic hematopoietic stem cell transplantation (allo-HSCT) after VEN-based salvage. VEN-based salvage yielded a 2-year OS of 42% for patients previously treated with 7+3 and 100% for those treated with LDAC. Documented bacterial infections occurred in 3/18 patients, with no fungal or viral infections. Both 30- and 60-day mortality rates were 0%, and median survival from initiation of VEN-based salvage was 298 days (range 39–1039).Discussion: VEN-based salvage therapy, compared with literature data for FLAG-IDA and MEC, demonstrated lower early mortality at 30 days (0% vs 7–15%) and 60 days (0% vs 15–20%), lower infection rates (17% vs ~50% documented infections/70–90% febrile neutropenia), and higher CR rates (71% vs ~55%). Outcomes with FLAG-IDA and MEC may be even worse in developing countries. Furthermore, while most patients in pivotal trials such as VIALE-A and VIALE-C were White, the majority in this study were self-identified as mixed-race or Black, demonstrating the effectiveness of this combination in this underrepresented population.Conclusion: In this real-world study, VEN-based salvage therapy induced rapid and high CR rates after 7+3 or LDAC, with a favorable safety profile, and may serve as a less-toxic bridge to allo-HSCT.
