Maintenance therapy with alternating azacitidine and lenalidomide in elderly fit patients with poor prognosis acute myeloid leukemia: a phase II multicentre FILO trial

Hunault, Mathilde; Maillard, Natacha; Himberlin, Chantal; Récher, Christian; Tanguy‐Schmidt, Aline; Choufi, Bachra; Bonmati, Caroline; Carré, Martin; Couturier, M-A; Marolleau, JP; Orsini‐Piocelle, Frédérique; Delaunay, Jacques; Tavernier, Emmanuelle; Lissandre, Séverine; Ojeda-Uribe, Mario; Sanhès, Laurence; Sutton, Laurent; Banos, Anne; Fornecker, Luc; Bernard, Marc; Bouscary, Didier; Saad, Alain; Puyade, Mathieu; Rouille, Valérie; Luquet, Isabelle; Béné, Marie C.; Hamel, J.F.; Dreyfus, François; Ifrah, Norbert; Pigneux, Arnaud

doi:10.1038/bcj.2017.50

Cited by 8 publications

(7 citation statements)

References 15 publications

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“…As far as intensive chemotherapy is concerned, our standard of care for older AML patients combines lomustine, idarubicin, and cytarabine . Lomustine is an alkylating agent with anti‐leukemic activity .…”

Section: Discussionmentioning

confidence: 99%

“…As far as intensive chemotherapy is concerned, our standard of care for older AML patients combines lomustine, idarubicin, and cytarabine. 15,16 Lomustine is an alkylating agent with anti-leukemic activity. 17 The FILO study group recently reported the significant impact of adding lomustine to idarubicin and cytarabine with a higher response rate and reduction in relapses resulting in better EFS and improved OS.…”

Section: Discussionmentioning

confidence: 99%

“…Median EFS, RFS and OS were 7 (IQR, 3-16), 8 (4-28), and 11 (5-29) months, respectively ( Figure 1). OS was 21% [95%CI: [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] and 17% [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] at 3 and 5 years, respectively. In allografted patients, median OS starting from allogeneic stem cell transplantation was 15 months (5-NR) whereas 3-year and 5-year OS were 50% [95%CI: .…”

Section: Outcome Of Patients Treated By Intensive Chemotherapymentioning

confidence: 99%

“…After censoring patients at the date of allogeneic stem cell transplantation, OS at 5 years was 14% [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] and 2% [0.2-9.3], in patients treated by intensive chemotherapy and HMA, respectively. In patients aged ≥ 70 years at diagnosis, OS at 5 years was 11% and 3% [0.3-14.3], in patients treated by intensive chemotherapy and HMA, respectively; whereas in patients aged < 70 years, OS at 5 years was 19% [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] and 0%, in patients treated by intensive chemotherapy and HMA, respectively.…”

Section: Subgroup Analysismentioning

confidence: 99%

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Outcome of patients aged 60‐75 years with newly diagnosed secondary acute myeloid leukemia: A single‐institution experience

et al. 2019

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A recent phase 3 trial showed that outcome of older patients with secondary acute myeloid leukemia ( AML ) may be improved by a liposomal encapsulation of cytarabine and daunorubicin ( CPX ‐351). This phase 3 study represents a unique example of prospective data in this rare subgroup providing basis for comparison with real life data. Here, we retrospectively assessed characteristics and outcome of patients aged 60‐75 years with secondary or therapy‐related AML in real life. Out of 218 patients that fulfilled CPX ‐351 study criteria, 181 patients (83.0%) received antileukemic treatment either intensive chemotherapy (n = 121) or hypomethylating agents ( HMA , n = 60). As compared with patients treated by chemotherapy, HMA ‐treated patients were older, had lower WBC , more often AML with antecedent myelodysplastic syndrome and adverse cytogenetic risk. In chemotherapy‐treated patients, the complete response rate was 69%, median overall survival ( OS ) was 11 months whereas 3‐year and 5‐year OS was 21% and 17%, respectively. In HMA ‐treated patients, the complete response rate was 15%, median OS was 11 months whereas 3‐year and 5‐year OS was 15% and 2%, respectively. In conclusion, although outcome of older patients with high‐risk AML is very poor, a significant proportion of patients treated by standard intensive chemotherapy but not HMA are long‐term survivors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Outcome Of Patients Treated By Intensive Chemotherapymentioning

confidence: 99%

Section: Subgroup Analysismentioning

confidence: 99%

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Outcome of patients aged 60‐75 years with newly diagnosed secondary acute myeloid leukemia: A single‐institution experience

et al. 2019

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“…The median OS was 10 months with a 2‐year OS rate of 21.4%. Relapse of AML occurred in 55 patients at a median time of 7 months, and 65% of them occurred during the maintenance . Therefore, despite the biological findings, this combination strategy did not improve outcomes of patients with AML in CR1.…”

Section: Trials Including Maintenance Therapy After Consolidation In mentioning

confidence: 90%

Maintenance therapy in AML: The past, the present and the future

et al. 2019

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Curative treatment in acute myeloid leukemia (AML) depends on successful induction therapy to achieve a complete remission (CR), and subsequent post‐remission therapy to prevent relapse. High relapse rates after consolidation therapy and after allogeneic stem cell transplant contribute to suboptimal outcomes in AML patients, and continue to represent a difficult challenge. Effective maintenance therapy could play an important role in prolonging the remission interval in the post‐consolidation setting, especially in high risk AML patients. Maintenance treatment approaches based on conventional chemotherapy, immunotherapy, hypomethylating agents, and targeted small molecules have been explored in this setting, but no data so far have been convincing enough to establish this approach as the standard of care. However, ongoing and future studies including novel targeted therapies may demonstrate promising efficacy that could facilitate incorporation of maintenance therapy into clinical practice. In this review we summarize previous and ongoing approaches of maintenance therapy in AML and discuss the most promising strategies.

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The DNA methylation landscape of hematological malignancies: an update

2020

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The rapid advances in high‐throughput sequencing technologies have made it more evident that epigenetic modifications orchestrate a plethora of complex biological processes. During the last decade, we have gained significant knowledge about a wide range of epigenetic changes that crucially contribute to some of the most aggressive forms of leukemia, lymphoma, and myelodysplastic syndromes. DNA methylation is a key epigenetic player in the abnormal initiation, development, and progression of these malignancies, often acting in synergy with other epigenetic alterations. It also contributes to the acquisition of drug resistance. In this review, we summarize the role of DNA methylation in hematological malignancies described in the current literature. We discuss in detail the dual role of DNA methylation in normal and aberrant hematopoiesis, as well as the involvement of this type of epigenetic change in other aspects of the disease. Finally, we present a comprehensive overview of the main clinical implications, including a discussion of the therapeutic strategies that regulate or reverse aberrant DNA methylation patterns in hematological malignancies, including their combination with (chemo)immunotherapy.

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Maintenance therapy with alternating azacitidine and lenalidomide in elderly fit patients with poor prognosis acute myeloid leukemia: a phase II multicentre FILO trial

Cited by 8 publications

References 15 publications

Outcome of patients aged 60‐75 years with newly diagnosed secondary acute myeloid leukemia: A single‐institution experience

Outcome of patients aged 60‐75 years with newly diagnosed secondary acute myeloid leukemia: A single‐institution experience

Maintenance therapy in AML: The past, the present and the future

The DNA methylation landscape of hematological malignancies: an update

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