Venetoclax-based salvage therapy followed by Venetoclax and DLI maintenance vs. FLAG-Ida for relapsed or refractory acute myeloid leukemia after allogeneic stem cell transplantation

Žučenka, Andrius; Vaitekėnaitė, Vilmantė; Maneikis, Kazimieras; Davainis, Linas; Pileckyte, Regina; Trociukas, Igoris; Pečeliūnas, Valdas; Žvirblis, Tadas; Staras, Vytautas; Griškevičius, Laimonas

doi:10.1038/s41409-021-01416-5

Cited by 17 publications

(15 citation statements)

References 34 publications

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“…This is of importance since many of post-alloHSCT r/r AML patients are not eligible for further intensive salvage treatment. A retrospective analysis of 20 post-alloHSCT relapse patients showed a CRc rate of 70% when treated with a combination therapy consisting of VEN, LDAC and Actinomycin D (Zucenka et al 2021 ). Another recently published retrospective study on r/r AML patients after alloHSCT including 29 patients demonstrated an ORR of 38% with a median OS of 2.6 months (Joshi et al 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Clinical experience with venetoclax in patients with newly diagnosed, relapsed, or refractory acute myeloid leukemia

Fleischmann

Scholl

Frietsch

et al. 2022

J Cancer Res Clin Oncol

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Background Diagnosis of acute myeloid leukemia (AML) is associated with poor outcome in elderly and unfit patients. Recently, approval of the BCL-2 inhibitor venetoclax (VEN) in combination with hypo-methylating agents (HMA) led to a significant improvement of response rates and survival. Further, application in the relapsed or refractory (r/r) AML setting or in context of allogeneic stem cell transplantation (alloHSCT) seems feasible. Methods and patients Fifty-six consecutive adult AML patients on VEN from January 2019 to June 2021 were analyzed retrospectively. Patients received VEN either as first-line treatment, as subsequent therapy (r/r AML excluding prior alloHSCT), or at relapse after alloHSCT. VEN was administered orally in 28-day cycles either combined with HMA or low-dose cytarabine (LDAC). Results After a median follow-up of 11.5 (range 6.1–22.3) months, median overall survival (OS) from start of VEN treatment was 13.3 (2.2–20.5) months, 5.0 (0.8–24.3) months and 4.0 (1.5–22.1) months for first-line, subsequent line treatment and at relapse post-alloHSCT, respectively. Median OS was 11.5 (10–22.3) months from start of VEN when subsequent alloHSCT was carried out. Relapse-free survival (RFS) for the total cohort was 10.2 (2.2 – 24.3) months. Overall response rate (composite complete remission + partial remission) was 51.8% for the total cohort (61.1% for VEN first-line treatment, 52.2% for subsequent line and 42.8% at relapse post-alloHSCT). Subgroup analysis revealed a significantly reduced median OS in FLT3-ITD mutated AML with 3.4 (1.9–4.9) months versus 10.4 (0.8–24.3) months for non-mutated cases, (HR 4.45, 95% CI 0.89–22.13, p = 0.0002). Patients harboring NPM1 or IDH1/2 mutations lacking co-occurrence of FLT3-ITD showed a survival advantage over patients without those mutations (11.2 (5–24.3) months versus 5.0 (0.8–22.1) months, respectively, (HR 0.53, 95% CI 0.23 – 1.21, p = 0.131). Multivariate analysis revealed mutated NPM1 as a significant prognostic variable for achieving complete remission (CR) (HR 19.14, 95% CI 2.30 – 436.2, p < 0.05). The most common adverse events were hematological, with grade 3 and 4 neutropenia and thrombocytopenia reported in 44.6% and 14.5% of patients, respectively. Conclusion Detailed analyses on efficacy for common clinical scenarios, such as first-line treatment, subsequent therapy (r/r AML), and application prior to and post-alloHSCT, are presented. The findings suggest VEN treatment combinations efficacious not only in first-line setting but also in r/r AML. Furthermore, VEN might play a role in a subgroup of patients with failure to conventional chemotherapy as a salvage regimen aiming for potential curative alloHSCT.

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Section: Discussionmentioning

confidence: 99%

Clinical experience with venetoclax in patients with newly diagnosed, relapsed, or refractory acute myeloid leukemia

Fleischmann

Scholl

Frietsch

et al. 2022

J Cancer Res Clin Oncol

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“…On the contrary, no CR was reported in patients who received a prior allogenic HSCT in a single-center analysis of 21 patients with a R/R myeloid malignancy ( n = 20 AML and n = 1 MDS) treated with the combination of VEN + HMA ( n = 8) or VEN + LDAC ( n = 16), reported an ORR of 28.6% (95% CI: 11.3–52.2%) ( n = 6). Zucenka et al [ 75 ] compared the outcome of R/R patients after alloSCT treated with VEN + LDAC + actinomycin D ( n = 20) with those receiving fludarabine + cytarabine + idarubicin (FLAG-Ida; n = 29). Patients treated with the VEN regimen obtained better results compared to the FLAG-Ida group (ORR 75% vs. 66%; p = 0.542; CR/CRi rate 70% vs. 34%; p = 0.02; OS 13.1 vs. 5.1 months; p = 0.032).…”

Section: Clinical Evidence In R/r Amlmentioning

confidence: 99%

Venetoclax in Relapsed/Refractory Acute Myeloid Leukemia: Are Supporting Evidences Enough?

Brancati

Gozzo

Romano

et al. 2021

Cancers

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Despite the progress in the development of new therapeutic strategies, relapsed/refractory (R/R) acute myeloid leukemia (AML) still represents a high unmet medical need. Treatment options in this setting include enrollment into clinical trials, allogeneic stem cell transplantation and/or targeted therapy. Nevertheless, it is associated with poor outcomes. Thus, the development of new treatments, which could ameliorate the prognosis of these patients with a good safety profile are highly demanded. Recently, venetoclax (VEN) has been approved for naïve AML patients unfit for intensive chemotherapy. In this regard, regimens including VEN could represent a valuable treatment option even in those with R/R disease and several studies have been conducted to demonstrate its role in this clinical setting. This review aims to summarize the current evidence on the use of VEN regimens in the treatment of R/R AML.

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“…5 In addition, VEN-based combination therapy (VEN, low-dose Cytarabine, Actinomycin D, and DLI maintenance) treatment exhibited a 70% CR/CRp rate in relapsed AML patients after HSCT (80% of these patients relapsed within 1-year post-transplantation). 6 These results suggest that combining VEN with other therapies may have a synergistic treatment effect for early post-transplant relapse.…”

Section: E44 Correspondencementioning

confidence: 86%

Venetoclax plus hypomethylating agent for the salvage treatment of relapsing myeloid malignancies after hematopoietic stem cell transplantation: A multicenter retrospective study on behalf of the Zhejiang Cooperative Group for Blood and Marrow Transplantation

Gao

Luo

et al. 2021

American J Hematol

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Venetoclax-based salvage therapy followed by Venetoclax and DLI maintenance vs. FLAG-Ida for relapsed or refractory acute myeloid leukemia after allogeneic stem cell transplantation

Cited by 17 publications

References 34 publications

Clinical experience with venetoclax in patients with newly diagnosed, relapsed, or refractory acute myeloid leukemia

Clinical experience with venetoclax in patients with newly diagnosed, relapsed, or refractory acute myeloid leukemia

Venetoclax in Relapsed/Refractory Acute Myeloid Leukemia: Are Supporting Evidences Enough?

Venetoclax plus hypomethylating agent for the salvage treatment of relapsing myeloid malignancies after hematopoietic stem cell transplantation: A multicenter retrospective study on behalf of the Zhejiang Cooperative Group for Blood and Marrow Transplantation

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