Venetoclax plus decitabine induced complete remission with molecular response in acute myeloid leukemia relapsed after hematopoietic stem cell transplantation

Andreani, Giacomo; Dragani, Matteo; Serra, Anna; Nicoli, Paolo; Gobbi, Marco De; Cilloni, Daniela

doi:10.1002/ajh.25352

Cited by 6 publications

(6 citation statements)

References 9 publications

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“…1B ) and dead leukemia patients (Fig. 1C ), which has allowed the use of venetoclax in the leukemia patients; meanwhile, its clinical application in AML treatment is also introduced [ 9 , 10 ]. Azacitidine is a hypomethylating agent recommended as a front-line therapeutic for the elderly AML patients who are not eligible for the intensive regimen and is also approved for treating the adult patients [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Venetoclax plus azacitidine and donor lymphocyte infusion in treating acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation

Zhao

et al. 2021

Ann Hematol

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This study aimed to evaluate the efficacy and safety of venetoclax plus azacitidine and donor lymphocyte infusion (DLI) in treating patients with relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Twenty-six AML patients who relapsed after allo-HSCT were enrolled and treated with venetoclax plus azacitidine and DLI. Complete remission with incomplete recovery (CRi), partial remission (PR), and objective remission rate (ORR) were assessed, and then event-free survival (EFS) and overall survival (OS) were evaluated. Besides, adverse events were documented. Additionally, whole exome sequencing was performed in bone marrow samples. The CRi, PR, and ORR rates were 26.9%, 34.6%, and 61.5%, respectively. The median time of EFS and OS was 120 (95% CI: 71–610) days and 284.5 (95% CI: 81–610) days, respectively. The most common adverse events were hematologic system adverse events including agranulocytosis, anemia, and thrombocytopenia, while the adverse events of other systems were relatively less and milder. In addition, no serious adverse events existed. Of note, there were 6 (23.1%) patients who developed GVHD. As for gene mutation, 49 mutated genes were found, which were categorized as first-, second-, and third-class mutations, and then further analysis revealed that the first-class mutations were not correlated with EFS or OS. Additionally, the most frequent mutated genes were FLT3, CEBPA, DNMT3A, KIT, KRAS, and NRAS. Venetoclax plus azacitidine and DLI is efficient and tolerant in treating patients with relapsed AML after allo-HSCT, implying this combined therapy as a potential treatment option in the studied patients.

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Section: Introductionmentioning

confidence: 99%

Venetoclax plus azacitidine and donor lymphocyte infusion in treating acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation

Zhao

et al. 2021

Ann Hematol

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“…One patient who also received DLI developed cGvHD and had to be treated with low-dose oral steroids. The immunologic effects of DLI seem not to be reinforced by HMAClax; however, others published single cases of GvHD after treatment with HMAClax and DLI [25,27,28].…”

Section: Discussionmentioning

confidence: 97%

“…We here report a retrospective multi-center experience on the use of a combination of hypomethylating agents and the BCL2-inhibitor venetoclax for the treatment of relapse after alloHSCT. Earlier reports have included smaller groups of patients relapsing after alloHSCT so far [25][26][27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Treatment of myeloid malignancies relapsing after allogeneic hematopoietic stem cell transplantation with venetoclax and hypomethylating agents—a retrospective multicenter analysis on behalf of the German Cooperative Transplant Study Group

et al. 2020

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Treatment of relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) remains a great challenge. Aiming to evaluate the combination of venetoclax and hypomethylating agents (HMAClax) for the treatment of relapse of myeloid malignancies after alloHSCT, we retrospectively collected data from 32 patients treated at 11 German centers. Venetoclax was applied with azacitidine (n = 13) or decitabine (n = 19); 11 patients received DLI in addition. HMAClax was the first salvage therapy in 8 patients. The median number of cycles per patient was 2 (1–19). All but 1 patient had grade 3/4 neutropenia. Hospital admission for grade 3/4 infections was necessary in 23 patients (72%); 5 of these were fatal. In 30 evaluable patients, overall response rate (ORR) was 47% (14/30, 3 CR MRDneg, 5 CR, 2 CRi, 1 MLFS, 3 PR). ORR was 86% in first salvage patients versus 35% in later salvage patients (p = 0.03). In 6 patients with molecular relapse (MR), ORR was 67% versus 42% in patients with hematological relapse (HR) (n = 24, p = n.s.). After a median follow-up of 8.4 months, 25 patients (78%) had died and 7 were alive. Estimated median overall survival was 3.7 months. Median survival of patients with HMAClax for first versus later salvage therapy was 5.7 and 3.4 months (p = n.s.) and for patients with MR (not reached) compared to HR (3.4 months, p = 0.024). This retrospective case series shows that venetoclax is utilized in various different combinations, schedules, and doses. Toxicity is substantial and patients who receive venetoclax/HMA combinations for MR or as first salvage therapy derive the greatest benefit.

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“…Epigenetic dysregulation plays a major role in leukemogenesis [36][37][38][39]. Hypomethylating agents have been shown to be active in AML as a single agent as well as in combination regimens [40][41][42][43][44][45][46]. A multicenter, openlabel, 3-arm study is being done to compare gilteritinib, gilteritinib plus azacitidine (AZA), or azacitidine alone in newly diagnosed FLT3 mutated (FLT3 mut+) AML patients who are unfit for intensive induction chemotherapy (NCT02752035).…”

Section: Gilteritinib In Combination Regimensmentioning

confidence: 99%

Gilteritinib: a novel FLT3 inhibitor for acute myeloid leukemia

2019

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FMS-like tyrosine kinase 3- internal tandem duplication (FLT3-ITD) remains as one of the most frequently mutated genes in acute myeloid leukemia (AML), especially in those with normal cytogenetics. The FLT3-ITD and FLT3-TKD (tyrosine kinase domain) mutations are biomarkers for high risk AML and are associated with drug resistance and high risk of relapse. Multiple FLT3 inhibitors are in clinical development, including lestaurtinib, tandutinib, quizartinib, midostaurin, gilteritinib, and crenolanib. Midostaurin and gilteritinib have been approved by FDA for Flt3 mutated AML. Gilteritinib (ASP2215, Xospata) is a small molecule dual inhibitor of FLT3/AXL. The ADMIRAL study showed that longer overall survival and higher response rate are associated with gilteritinib in comparison with salvage chemotherapy for relapse /refractory (R/R) AML. These data from the ADMIRAL study may lead to the therapy paradigm shift and establish gilteritinib as the new standard therapy for R/R FLT3-mutated AML. Currently, multiple clinical trials are ongoing to evaluate the combination of gilteritinib with other agents and regimens. This study summarized clinical trials of gilteritinib for AML.

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Venetoclax plus decitabine induced complete remission with molecular response in acute myeloid leukemia relapsed after hematopoietic stem cell transplantation

Cited by 6 publications

References 9 publications

Venetoclax plus azacitidine and donor lymphocyte infusion in treating acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation

Venetoclax plus azacitidine and donor lymphocyte infusion in treating acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation

Treatment of myeloid malignancies relapsing after allogeneic hematopoietic stem cell transplantation with venetoclax and hypomethylating agents—a retrospective multicenter analysis on behalf of the German Cooperative Transplant Study Group

Gilteritinib: a novel FLT3 inhibitor for acute myeloid leukemia

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