Maintenance lenalidomide in combination with 5-azacitidine as post-remission therapy for acute myeloid leukaemia

Andrew Wei, Peter Thian Guan Tan, Sarah Nicole Perruzza, Chindu Govindaraj, Shaun Alan Fleming, Julie F McManus, Sharon Avery, Sushrut Patil, William C Stevenson, Magdalena Plebanski, Andrew Spencer

Research output: Contribution to journalArticleResearchpeer-review

Abstract

In this Phase 1b study, the safety and tolerability of maintenance therapy, comprising lenalidomide (0-25 mg, days 5-25) in combination with azacitidine (50-75 mg/m2, days 1-5) every 28 d, was explored in 40 patients with acute myeloid leukaemia (AML) in complete remission after chemotherapy. Eligibility included AML in first complete remission (CR1) with adverse risk karyotype (n = 8), fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) (n = 5), age =60 years (n = 31) or AML in second remission (CR2) (n = 14). Dose-limiting toxicity was not reached. Common toxicities were haematological, infection, injection pain, constipation, fatigue and diarrhoea. In CR1, median relapse-free (RFS) and overall survival (OS) was 12 and 20 months, respectively. In CR2, median RFS was 11 months, with median OS not yet reached. Among 29 patients with intermediate cytogenetic risk, RFS was 50 at 24 months. There were five patients with concomitant FLT3-ITD and nucleophosmin (NPM1) mutation; none have relapsed and all are still alive after 17-39 months. Maintenance lenalidomide/azacitidine augmented the function of cytotoxic T lymphocytes, particularly in patients with NPM1 mutation. The lenalidomide/azacitidine maintenance combination was effective in suppressing residual DNA (cytosine-5-)-methyltransferase 3 alpha (DNMT3A)-positive disease, resulting in sustained remission in patients with concurrent NPM1 mutation. Azacitidine/lenalidomide as maintenance therapy for high-risk AML warrants further exploration.
Original languageEnglish
Pages (from-to)199 - 210
Number of pages12
JournalBritish Journal of Haematology
Volume169
Issue number2
DOIs
Publication statusPublished - 2015

Cite this

Wei, Andrew ; Tan, Peter Thian Guan ; Perruzza, Sarah Nicole ; Govindaraj, Chindu ; Fleming, Shaun Alan ; McManus, Julie F ; Avery, Sharon ; Patil, Sushrut ; Stevenson, William C ; Plebanski, Magdalena ; Spencer, Andrew. / Maintenance lenalidomide in combination with 5-azacitidine as post-remission therapy for acute myeloid leukaemia. In: British Journal of Haematology. 2015 ; Vol. 169, No. 2. pp. 199 - 210.
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title = "Maintenance lenalidomide in combination with 5-azacitidine as post-remission therapy for acute myeloid leukaemia",
abstract = "In this Phase 1b study, the safety and tolerability of maintenance therapy, comprising lenalidomide (0-25 mg, days 5-25) in combination with azacitidine (50-75 mg/m2, days 1-5) every 28 d, was explored in 40 patients with acute myeloid leukaemia (AML) in complete remission after chemotherapy. Eligibility included AML in first complete remission (CR1) with adverse risk karyotype (n = 8), fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) (n = 5), age =60 years (n = 31) or AML in second remission (CR2) (n = 14). Dose-limiting toxicity was not reached. Common toxicities were haematological, infection, injection pain, constipation, fatigue and diarrhoea. In CR1, median relapse-free (RFS) and overall survival (OS) was 12 and 20 months, respectively. In CR2, median RFS was 11 months, with median OS not yet reached. Among 29 patients with intermediate cytogenetic risk, RFS was 50 at 24 months. There were five patients with concomitant FLT3-ITD and nucleophosmin (NPM1) mutation; none have relapsed and all are still alive after 17-39 months. Maintenance lenalidomide/azacitidine augmented the function of cytotoxic T lymphocytes, particularly in patients with NPM1 mutation. The lenalidomide/azacitidine maintenance combination was effective in suppressing residual DNA (cytosine-5-)-methyltransferase 3 alpha (DNMT3A)-positive disease, resulting in sustained remission in patients with concurrent NPM1 mutation. Azacitidine/lenalidomide as maintenance therapy for high-risk AML warrants further exploration.",
author = "Andrew Wei and Tan, {Peter Thian Guan} and Perruzza, {Sarah Nicole} and Chindu Govindaraj and Fleming, {Shaun Alan} and McManus, {Julie F} and Sharon Avery and Sushrut Patil and Stevenson, {William C} and Magdalena Plebanski and Andrew Spencer",
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Maintenance lenalidomide in combination with 5-azacitidine as post-remission therapy for acute myeloid leukaemia. / Wei, Andrew; Tan, Peter Thian Guan; Perruzza, Sarah Nicole; Govindaraj, Chindu; Fleming, Shaun Alan; McManus, Julie F; Avery, Sharon; Patil, Sushrut; Stevenson, William C; Plebanski, Magdalena; Spencer, Andrew.

In: British Journal of Haematology, Vol. 169, No. 2, 2015, p. 199 - 210.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Maintenance lenalidomide in combination with 5-azacitidine as post-remission therapy for acute myeloid leukaemia

AU - Wei, Andrew

AU - Tan, Peter Thian Guan

AU - Perruzza, Sarah Nicole

AU - Govindaraj, Chindu

AU - Fleming, Shaun Alan

AU - McManus, Julie F

AU - Avery, Sharon

AU - Patil, Sushrut

AU - Stevenson, William C

AU - Plebanski, Magdalena

AU - Spencer, Andrew

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N2 - In this Phase 1b study, the safety and tolerability of maintenance therapy, comprising lenalidomide (0-25 mg, days 5-25) in combination with azacitidine (50-75 mg/m2, days 1-5) every 28 d, was explored in 40 patients with acute myeloid leukaemia (AML) in complete remission after chemotherapy. Eligibility included AML in first complete remission (CR1) with adverse risk karyotype (n = 8), fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) (n = 5), age =60 years (n = 31) or AML in second remission (CR2) (n = 14). Dose-limiting toxicity was not reached. Common toxicities were haematological, infection, injection pain, constipation, fatigue and diarrhoea. In CR1, median relapse-free (RFS) and overall survival (OS) was 12 and 20 months, respectively. In CR2, median RFS was 11 months, with median OS not yet reached. Among 29 patients with intermediate cytogenetic risk, RFS was 50 at 24 months. There were five patients with concomitant FLT3-ITD and nucleophosmin (NPM1) mutation; none have relapsed and all are still alive after 17-39 months. Maintenance lenalidomide/azacitidine augmented the function of cytotoxic T lymphocytes, particularly in patients with NPM1 mutation. The lenalidomide/azacitidine maintenance combination was effective in suppressing residual DNA (cytosine-5-)-methyltransferase 3 alpha (DNMT3A)-positive disease, resulting in sustained remission in patients with concurrent NPM1 mutation. Azacitidine/lenalidomide as maintenance therapy for high-risk AML warrants further exploration.

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