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. 2024 Jan 1;109(1):72-83.
doi: 10.3324/haematol.2023.282912.

Fludarabine, cytarabine, and idarubicin with or without venetoclax in patients with relapsed/refractory acute myeloid leukemia

Rabia Shahswar  1 , Gernot Beutel  1 , Razif Gabdoulline  1 , Adrian Schwarzer  1 , Arnold Kloos  1 , Christian Koenecke  1 , Michael Stadler  1 , Gudrun Gohring  2 , Yvonne Lisa Behrens  2 , Zhixiong Li  1 , Louisa-Kristin Dallmann  1 , Piroska Klement  1 , Catherin Albert  1 , Martin Wichmann  1 , Yasmine Alwie  1 , Axel Benner  3 , Maral Saadati  4 , Arnold Ganser  1 , Felicitas Thol  1 , Michael Heuser  5
Affiliations

Fludarabine, cytarabine, and idarubicin with or without venetoclax in patients with relapsed/refractory acute myeloid leukemia

Rabia Shahswar et al. Haematologica. .

Abstract

Treatment options for relapsed and refractory acute myeloid leukemia patients (R/R AML) are limited. This retrospective cohort study compares safety and efficacy of fludarabine, cytarabine, and idarubicin (FLA-IDA) without or with venetoclax (FLAVIDA) in patients with R/R AML. Thirty-seven and 81 patients received one course FLA-IDA with or without a 7-day course of venetoclax, respectively. The overall response rate (ORR) was significantly higher in FLAVIDA compared to FLAIDA- treated patients (78% vs. 47%; P=0.001), while measurable residual disease was negative at a similar proportion in responding patients (50% vs. 57%), respectively. Eighty-one percent and 79% of patients proceeded to allogeneic hematopoietic cell transplantation or donor lymphocyte infusion after FLAVIDA and FLA-IDA, respectively. Event-free and overall survival were similar in FLAVIDA- and FLA-IDA-treated patients. Refractory patients could be salvaged more successfully after FLA-IDA compared to FLAVIDA pretreatment. Neutrophil and platelet recovery times were similar in the venetoclax and the control group. In conclusion, short-term venetoclax in combination with FLA-IDA represents an effective treatment regimen in R/R AML identifying chemosensitive patients rapidly and inducing measurable residual disease-negative remission in a high proportion of R/R AML patients.

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Figures

Figure 1.
Figure 1.
Frequency of complete remission, complete remission with incomplete hematological recovery, morphologic leukemia-free state, and overall response rate in FLAVIDA- (N=37) and FLA-IDA- (N=81) treated patients. FLA-IDA: fludarabine, cytarabine, and idarubicin; FLAVIDA: FLA-IDA with venetoclax; CR: complete remission; CRi: complete remission with incomplete hematological recovery; MLFS: morphologic leukemia-free state; ORR: overall response rate; CI: confidence interval.
Figure 2.
Figure 2.
Impact of patient and disease characteristics on achieving overall response in FLAVIDA and FLA-IDA patients. TP53 status not shown due to small number of mutated patients (FLAVIDA TP53mut N=2; FLA-IDA TP53mut N=4). FLA-IDA: fludarabine, cytarabine, and idarubicin; FLAVIDA: FlA-IDA with venetoclax; CI: confidence interval; sAML: secondary acute myeloid leukemia; tAML: therapy-related AML; ELN: European LeukemiaNet.
Figure 3.
Figure 3.
Survival outcomes in FLAVIDA- and FLA-IDA-treated patients. (A) Inverse probability of preatment weighted Kaplan Meier curves of overall survival (OS) in FLAVIDA- and FLA-IDA-treated patients. (B) Inverse probability of treatment weighted Kaplan Meier curves of event-free survival (EFS) in FLAVIDA- and FLA-IDA-treated patients. FLA-IDA: fludarabine, cytarabine, and idarubicin; FLAVIDA: FlA-IDA with venetoclax; HR: hazard ratio; CI: confidence interval.
Figure 4.
Figure 4.
Survival outcomes in FLAVIDA- and FLA-IDA-treated patients depending on measurable residual disease status. (A) Overall survival (OS) in FLAVIDA-treated patients with measurable residual disease (MRD)-negative or MRD-positive overall response (including CR, CRi, and MLFS). Landmark analysis was performed from time of overall response. (B) OS in FLA-IDA-treated patients with MRD-negative or MRD-positive overall response (including CR, CRi, and MLFS). Landmark analysis was performed from time of overall response. (C) Relapse-free survival in FLAVIDA patients with MRD-negative or MRD-positive CR/CRi. Landmark analysis was performed from time of CR/CRi. (D) Relapse-free survival in FLA-IDA patients with MRD-negative or MRD-positive CR/CRi. Landmark analysis was performed from time of CR/Cri. FLA-IDA: fludarabine, cytarabine, and idarubicin; FLAVIDA: FlA-IDA with venetoclax; CR: complete remission; CRc: composite complete remission; CRi: complete remission with incomplete hematological recovery; MLFS: morphologic leukemia free state
Figure 5.
Figure 5.
Overall survival in non-responding FLAVIDA- or FLA-IDA-treated patients. Landmark analysis was performed from time of first response assessment. OS: overall survival; HR: hazard ratio; CI: confidence interval. FLA-IDA: fludarabine, cytarabine, and idarubicin; FLAVIDA: FlA-IDA with venetoclax.
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References

    1. Döhner H, Wei AH, Appelbaum FR, et al. . Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345-1377. - PubMed
    1. Walter RB, Othus M, Burnett AK, et al. . Resistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOG and MD Anderson Cancer Center. Leukemia. 2015;29(2):312-320. - PMC - PubMed
    1. Heuser M, Ofran Y, Boissel N, et al. . Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up [published correction appears in Ann Oncol. 2021;32(6):821]. Ann Oncol. 2020;31(6):697-712. - PubMed
    1. Thol F, Heuser M. Treatment for relapsed/refractory cute myeloid leukemia. Hemasphere. 2021;5(6):e572. - PMC - PubMed
    1. Nath R, Reddy V, Kapur A, et al. . Survival of relapsed/refractory acute myeloid leukemia (R/R AML) patients receiving stem cell transplantation (SCT). Biol Blood Marrow Transplant. 2019;25(3):S125.

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