A retrospective comparison of salvage intensive chemotherapy <i>versus</i> venetoclax-combined regimen in patients with relapsed/refractory acute myeloid leukemia (AML)

Park, Silvia; Kwag, Daehun; Lee, Jong Hyuk; Lee, Joon Yeop; Min, Gi June; Yoon, Jae‐Ho; Yahng, Seung‐Ah; Jeon, Young‐Woo; Shin, Sohee; Lee, Sung‐Eun; Cho, Byung Sik; Eom, Ki‐Seong; Kim, Yoo-Jin; Lee, Seok; Min, Chang‐Ki; Cho, Seok-Goo; Lee, Jong Wook; Kim, Hee-Je

doi:10.1177/20406207221081637

Cited by 9 publications

(18 citation statements)

References 63 publications

(101 reference statements)

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“…The DEC + VEN group received the same daily dose of DEC for five days combined with 28 days of VEN (400 mg daily) per cycle. The cycle 1 ramp-up, disease response evaluation, VEN dose reduction in concomitant with azoles, and the resting period between cycles were the same as in the VIALE-A trial [ 11 , 14 , 15 ]. We induced cytoreduction of white blood cell (WBC) counts <20 × 10 9 /L by hydroxyurea, low-dose intravenous cytarabine, or leukapheresis before DEC or DEC + VEN treatment.…”

Section: Methodsmentioning

confidence: 99%

“…Uric acid reducing agents (allopurinol, febuxostat, or rasburicase) and intravenous fluid hydration were administered for the prevention of tumor lysis syndrome. We used fluconazole 400 mg/day during the neutropenic period in all patients as antifungal prophylaxis without antibacterial prophylaxis [ 14 , 15 ]. DEC and DEC + VEN treatments were maintained until disease progression, a severe adverse event, a hematopoietic stem cell transplantation (HSCT), or the patient requested discontinuation.…”

Section: Methodsmentioning

confidence: 99%

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Venetoclax with decitabine versus decitabine monotherapy in elderly acute myeloid leukemia: a propensity score-matched analysis

et al. 2022

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Venetoclax (VEN) combined with azacitidine (AZA) or decitabine (DEC) has been approved for older adults with acute myeloid leukemia (AML) unfit for intensive chemotherapy based on the pivotal VIALE-A trial. However, this trial only compared AZA + VEN with AZA monotherapy. Therefore, we compared the outcomes of consecutive older adults (65 years or older) with newly diagnosed AML who received DEC (n = 230) or DEC + VEN (n = 74) after propensity score matching to construct a one-to-one matched cohort by the nearest neighbor algorithm. The median overall survival was longer in the DEC + VEN group than in the DEC group (13.4 months vs. 8.3 months, p = 0.01). The median event-free survivals were 8.6 and 5.8 months in the DEC + VEN and DEC groups, respectively (p = 0.02). The response rate (complete response, complete response with incomplete hematologic recovery, and morphologic leukemia-free state) was significantly higher in the DEC + VEN group than in the DEC group (70.3% vs. 24.3%, p < 0.01). The 30-day (2.7% vs. 9.5%, p = 0.17) and 60-day (9.5% vs. 18.9%, p = 0.16) mortality rates did not differ between the two groups, nor did the median hospitalization and transfusion rates (hospitalization: 23 days vs. 21 days, p = 0.20; red blood cells: 3.2 units/month vs. 3.5 units/month, p = 0.73; platelets: 2.7 units/month vs. 2.3 units/months, p = 0.48). Of those who received DEC + VEN and became leukemia-free, 29% underwent allogeneic stem cell transplantation and had excellent survival outcomes (one-year survival: 79.4%; one-year non-relapse mortality: 13.3%). This study is the first to provide real-world evidence that DEC + VEN has superior outcomes to DEC monotherapy.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Venetoclax with decitabine versus decitabine monotherapy in elderly acute myeloid leukemia: a propensity score-matched analysis

et al. 2022

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“…Through data mining FAERS, the new and rare AEs can be evaluated and detected. Compared with the previous clinical studies on VEN [18][19][20][21], this study was based on a large sample size and a long time span, and found new AE signals, filling the gap in the study of VEN related AEs in the real world. It is of great significance to understand the safety of VEN.…”

Section: Discussionmentioning

confidence: 97%

“…Our research results also show that off-label use accounts for 12.2% (2,339/19,107) of the total number of reports, which indicates that off-label use seems to be very common in clinical use of VEN. The AML is the most indication, accounting for more than 1/3, CLL is close to 1/3, and the remaining 1/3 are currently unapproved indications [ 20 , 21 , 42 ]. Although off-label use gives patients hope and some efficacy, it also brings a higher risk of AEs than conventional use, which requires careful evaluation and treatment by clinicians [ 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

A real-world pharmacovigilance study of FDA Adverse Event Reporting System (FAERS) events for venetoclax

et al. 2022

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Background Venetoclax (VEN) is the first selective small molecule Bcl-2 inhibitor approved by FDA and used in adult chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL) and some acute myeloid leukemia (AML). However, the long-term safety of VEN in large sample population was unknown. This study evaluated the adverse events (AEs) of VEN from FDA Adverse Event Reporting System (FAERS) since its approval in 2016 by data mining. Methods The disproportionality analyses, including four algorithms of reporting odd ratio (ROR), proportional reporting ratio (PRR), bayesian configuration promotion neural network (BCPNN), and multi item gamma poisson shrinker (MGPS), were employed to quantify the signals of VEN-associated AEs. Results From the FAERS database, a total of 8,379,682 reports were collected during the study period. After removing the duplication, the number of reports with VEN as the primary suspect (PS) was 19,107. The 19,107 cases of AEs involved 27 organ systems, 256 significant PTs which conforming to the four algorithms. Unexpected serious AEs, such as pleural effusion, splenic infarction, atrial fibrillation, skin squamous cell carcinoma, etc., have signals. The median time of occurrence of AEs related to VEN was 31 days (inter quartile range [IQR] 7–131 days), and half of the reported AEs occurred within 1 month after administration. Conclusion Our research has found new significant AEs signals of VEN, which improved its safety information in real-world after marketing approval, and contributed to its risk control of use in clinic.

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“…Although the approval for use is currently confined to patients with ND-AML, mounting evidence indicates increasing off-label use of these combinations to treat refractory/relapsed (R/R) AML because of their efficacy and safety profile. According to a series of reports [ 7 , 8 , 9 , 10 ], VEN-HMA combinations have yielded response rates as high as 64% in R/R-AML patients [ 8 ], which appears to be noninferior to results with salvage IC [ 10 ], even though the treatment intensity of the VEN combination is much lower than that of conventional cytotoxic salvage regimens.…”

Section: Introductionmentioning

confidence: 99%

A Successful Bridge Therapy Combining Hypomethylating Agents with Venetoclax for Adult Patients with Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia

Bang

Park

Kwag

et al. 2023

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Recently, the combination of VEN-HMA has been shown to achieve durable responses in patients with both newly diagnosed (ND) and R/R-AML. We retrospectively evaluated the post-allo-HCT outcomes of 50 patients who received VEN-HMA therapy. In total, 10 were ND and 40 were R/R and, at the time of HCT, the median age was 53 years. In the ND- and R/R-AML groups, the percentage of patients who achieved CR/CRi or MLFS was 90% and 92.5%, respectively. In all, after a median follow-up of 13.7 months, the probabilities of overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM) at 1 year were 63.7%, 59.3%, 28.5%, and 12.2%, respectively. In addition, the cumulative incidences of grade II–IV acute graft-versus-host disease (GVHD) and moderate–severe chronic GVHD at 1 year were 28.4% and 37.4%, respectively. In multivariate analysis, the factors associated with a statistically significant impact on OS were VEN-HMA cycle (p = 0.021), ELN risk group (p = 0.041), and the response to VEN-HMA therapy before allo-HCT (p = 0.003). Although 80% of our patients had R/R-AML and 30% underwent a second allo-HCT, our data still suggest that allo-HCT following VEN-HMA therapy is a safe and effective treatment option.

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A retrospective comparison of salvage intensive chemotherapy versus venetoclax-combined regimen in patients with relapsed/refractory acute myeloid leukemia (AML)

Cited by 9 publications

References 63 publications

Venetoclax with decitabine versus decitabine monotherapy in elderly acute myeloid leukemia: a propensity score-matched analysis

Venetoclax with decitabine versus decitabine monotherapy in elderly acute myeloid leukemia: a propensity score-matched analysis

A real-world pharmacovigilance study of FDA Adverse Event Reporting System (FAERS) events for venetoclax

A Successful Bridge Therapy Combining Hypomethylating Agents with Venetoclax for Adult Patients with Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia

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