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

Kwag, Daehun; Cho, Byung-Sik; Bang, Su-Yeon; Lee, Jong Hyuk; Min, Gi June; Park, Sung‐Soo; Park, Silvia; Yoon, Jae‐Ho; Lee, Sung‐Eun; Eom, Ki‐Seong; Kim, Yoo-Jin; Lee, Seok; Min, Chang‐Ki; Cho, Seok Goo; Lee, Jong Wook; Kim, Hee‐Je

doi:10.1038/s41408-022-00770-x

Cited by 17 publications

(14 citation statements)

References 35 publications

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“…However, although we cannot compare the outcomes between the two different HMA regimens in the current study, substantial data in both the new and R/R settings support the comparable or unsurpassed efficacy of DEC when combined to VEN [14,31,32]. In addition, we also observed promising results with DEC plus VEN in R/R AML setting in our previous study [24,33]. Some case reports have described more successful responses to VEN in EM relapse settings.…”

Section: Discussionsupporting

confidence: 50%

Limited Efficacy of Venetoclax Combination Regimens in Acute Myeloid Leukemia with Extramedullary Relapse

Bae,

Sa,

Park

et al. 2023

Acta Haematol

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The recently approved Bcl-2 inhibitor venetoclax (VEN) has achieved promising outcomes in new and relapsed/refractory (R/R) acute myeloid leukemia (AML). Although its use is not well-established in R/R AML with extramedullary disease (EMD), some reports have shown promising outcomes. We retrospectively analyzed 11 patients of R/R AML with EMD [with (n=4) or without (n=7) concurrent marrow involvement], who were treated with VEN plus decitabine (n=9) or low-dose cytarabine (n=2) between May 2020 and October 2020 in Seoul St. Mary’s Hospital. The median number of prior treatment lines was 3 (1-6) and most (n=9, 81.8%) had multiple sites of EMD. Nine patients (81.8%) received concurrent therapy for EM involvement sites with radiotherapy (RT) (n=4), surgery (n=1) and both of them (n=4). Among 11 patients, four patients (36.4%) had either marrow or EM responses to VEN-combination; EM response was seen in one patient (9.1%, partial response) who had received concurrent radiotherapy (25Gy, 10fx) during 1st cycle of VEN-combination, and other three patients showed marrow response without EM response. After median follow-up of 27.0 months, the median overall survival was estimated to be 5.4 months. To conclude, VEN-combination regimens have shown only modest efficacy in EM recurrence of AML with little impact on eliciting EM response.

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Section: Discussionsupporting

confidence: 50%

Limited Efficacy of Venetoclax Combination Regimens in Acute Myeloid Leukemia with Extramedullary Relapse

Bae,

Sa,

Park

et al. 2023

Acta Haematol

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“…A direct comparison with the study of DiNardo regarding these characteristics was not possible, as this information was not reported in the publication, or was displayed in a different way (e.g., percentage of patients with anemia instead of average level of hemoglobin). Eleven studies also provided information on the frequency of adverse events during treatment with VEN+HMAs, namely grade 3–4 neutropenia (range among the different studies: 29–93%), thrombocytopenia (range: 14–90%), febrile neutropenia (range 13–80%), tumor lysis syndrome (range: 0–12%) [ 21 , 24 , 26 , 27 , 28 , 29 , 32 , 33 , 35 , 36 , 42 ]. The percentages of patients who discontinued venetoclax because of adverse events ranged in the different studies between 7% and 66% ( Table S2 ).…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, although the trial of DiNardo et al reported a median overall survival of 14.7 months (95% CI 11.9-18.7), real-world studies showed substantially lower survival. With the only exception of Cherry et al and Mirgh et al, which reported a median survival of more than 15 months, the other authors showed an overall survival ranging between 4 and 13 months [21,24,[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42]. As a consequence, the pooled median survival in our meta-analysis was 9.37 months (95% CI 8.81-10.5), significantly lower than that reported by DiNardo et al This difference was also confirmed in the secondary analyses that we performed, in particular after we excluded studies enrolling subjects with worse prognoses (i.e., secondary, therapy-related, and TP53mutated AML).…”

Section: Discussionmentioning

confidence: 97%

Venetoclax with Hypomethylating Agents in Newly Diagnosed Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis of Survival Data from Real-World Studies

Ucciero,

Pagnoni,

Scotti

et al. 2023

Cancers

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In recent years, the association of venetoclax (VEN) with hypomethylating agents (HMAs) significantly improved the outcome of patients with newly diagnosed acute myeloid leukemia (AML) who were unfit for intensive chemotherapy and became the standard of care after the publication of the pivotal RCT VIALE-A. However, it is still not clear to what extent the results observed in the VIALE-A apply to a real-world setting. For this reason, we carried out a systematic review and meta-analysis of real-world studies on newly diagnosed patients with AML, ineligible for intensive induction chemotherapy, receiving first-line VEN+HMA. We then compared their results in term of survival with those from the VIALE-A. Kaplan-Meier curves were extracted from all included studies and individual survival data was reconstructed. We then estimated a pooled survival curve and compared it with the results of the VIALE-A using the log-rank test. We also conducted a secondary analysis including only studies considering VEN plus azacytidine (AZA) as treatment, as this was the schedule originally used in the VIALE-A. Nineteen real-world studies met the inclusion criteria and were included in the systematic review. Most of them reported a worse survival than the VIALE-A. The pooled survival curve was similar to that reported in the VIALE-A during the first three months of treatment but diverged thereafter (p-value = 0.0001). The pooled median survival among the real-world studies was 9.37 months (95%CI 8.81–10.5), substantially lower than that reported in the VIALE-A (14.7 months; 95%CI 11.9–18.7). Results slightly increased when the analysis was restricted to the studies using VEN+AZA as treatment (median survival: 11.5 months; 95%CI 10.2–14.8). Survival of newly diagnosed AML patients treated with VEN+HMAs in a real-world setting seems to be lower than previously reported in the VIALE-A, while the effect of VEN+AZA is more in line with expected results. Future studies are needed to evaluate whether this apparent discrepancy is due to the different characteristics of enrolled patients or to a non-optimal adherence to therapy, and whether alternative regimens can provide better results in terms of safety and effectiveness.

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“…BCL-2 is a key molecule in the regulation of apoptosis of tumor cells and is a novel target for the treatment of leukemia ( 28 ). The BCL-2 protein family is an important regulator of endogenous apoptotic pathways.…”

Section: Discussionmentioning

confidence: 99%

Meta‑analysis of the efficacy of venetoclax and azacitidine combination therapy and azacitidine monotherapy for treating acute myeloid leukemia

Xie,

Wei,

Wang

et al. 2024

Exp Ther Med

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The present study aimed to compare the efficacy of combination therapy with venetoclax and azacitidine with that of azacytidine monotherapy in the treatment of acute myeloid leukemia (AML). The Web of Science, PubMed, Embase, The Cochrane Library, Weipu Database, Wanfang Digital Periodicals, Sinomed, China National Knowledge Infrastructure, ProQuest Dissertations and Theses and Cumulative Index to Nursing and Allied Health Literature were searched for publications on the treatment of AML with venetoclax combined with azacitidine or with azacitidine monotherapy. A total of 5,271 relevant studies were retrieved, of which 10 were included. Literature quality was evaluated according to the Cochrane systematic review methodology, and data were extracted for meta-analysis using Review Manager 5.4. The combination of venetoclax and azacitidine demonstrated greater overall efficacy than azacitidine monotherapy for AML treatment. Notably, combination therapy resulted in a higher frequency of complete remission. By contrast, combined treatment and monotherapy showed no significant differences in partial remission, whereas there was a statistically significant decrease in the frequency of no remission in the combination therapy group compared with in the monotherapy group. The results also revealed a significantly higher incidence of adverse reactions when venetoclax and azacitidine were combined in the treatment of AML compared with the observed rates in response to azacitidine monotherapy. Moreover, subgroup analyses showed that no statistically significant differences were observed between the two groups regarding adverse events, including hypokalemia and liver insufficiency. In conclusion, the combination of venetoclax and azacitidine was more effective than azacitidine alone, and had a good clinical application value in the treatment of AML. Although some adverse reactions occurred in response to the combination therapy, they did not significantly affect the prognosis of AML. To better evaluate the efficacy and safety of this treatment regimen, multicenter clinical studies with larger sample sizes are required.

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

Cited by 17 publications

References 35 publications

Limited Efficacy of Venetoclax Combination Regimens in Acute Myeloid Leukemia with Extramedullary Relapse

Limited Efficacy of Venetoclax Combination Regimens in Acute Myeloid Leukemia with Extramedullary Relapse

Venetoclax with Hypomethylating Agents in Newly Diagnosed Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis of Survival Data from Real-World Studies

Meta‑analysis of the efficacy of venetoclax and azacitidine combination therapy and azacitidine monotherapy for treating acute myeloid leukemia

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