Hyper-CVAD plus nelarabine in newly diagnosed adult T-cell acute lymphoblastic leukemia and T-lymphoblastic lymphoma

Yasmin Abaza, Hagop M. Kantarjian, Stefan Faderl, Elias Jabbour, Nitin Jain, Deborah Thomas, Tapan Kadia, Gautam Borthakur, Joseph D. Khoury, Jan Burger, William Wierda, Susan O'Brien, Marina Konopleva, Alessandra Ferrajoli, Partow Kebriaei, Bouthaina Dabaja, Steven Kornblau, Yesid Alvarado, Naval Daver, Naveen PemmarajuPrithviraj Bose, Philip Thompson, Hind Al Azzawi, Mary Kelly, Rebecca Garris, Preetesh Jain, Guillermo Garcia-Manero, Jorge Cortes, Farhad Ravandi

Research output: Contribution to journalArticle

Abstract

Nelarabine, a water soluble prodrug of 9-β-D-arabinofuranosylguanine (ara-G), is a T-cell specific purine nucleoside analogue. Given its activity in relapsed and refractory T acute lymphoblastic leukemia (T-ALL) and T lymphoblastic lymphoma (T-LBL), we sought to define its role in the frontline treatment of adult patients. Therefore, we conducted a single arm phase 2 study to determine the safety and efficacy of nelarabine in combination with hyper-CVAD in newly diagnosed patients. For induction/consolidation, patients received eight cycles of hyper-CVAD alternating with high-dose methotrexate and cytarabine plus two cycles of nelarabine given at a dose of 650 mg/m2 intravenously daily for 5 days. This was followed by thirty months of POMP maintenance chemotherapy with two additional cycles of nelarabine given instead of cycles 6 and 7 of POMP maintenance. Sixty-seven patients, including 40 with T-ALL and 26 with T-LBL, were enrolled. Complete response rates in both T-ALL and T-LBL were 87% and 100% respectively. Grade 3 to 4 neurotoxic adverse events were reported in 5 patients. There were 21 relapses (31%) including 2 after allogeneic stem cell transplantation. Median duration of follow-up was 42.5 months. The 3-year complete remission duration (CRD) and overall survival (OS) rates were 66% and 65%, respectively. Compared to our historic hyper-CVAD data, there was no survival benefit with the addition of nelarabine. In conclusion, hyper-CVAD plus nelarabine was well tolerated and active in the frontline treatment of adult T-ALL/LBL patients.

Original languageEnglish (US)
Pages (from-to)91-99
Number of pages9
JournalAmerican Journal of Hematology
Volume93
Issue number1
DOIs
StatePublished - Jan 2018
Externally publishedYes

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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Precursor Cell Lymphoblastic Leukemia-Lymphoma
T-Lymphocytes
Maintenance Chemotherapy
Purine Nucleosides
Cytarabine
Prodrugs
Stem Cell Transplantation
nelarabine
Methotrexate
Survival Rate
Maintenance
Safety
Recurrence
Survival
Water
Therapeutics

ASJC Scopus subject areas

  • Hematology

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Hyper-CVAD plus nelarabine in newly diagnosed adult T-cell acute lymphoblastic leukemia and T-lymphoblastic lymphoma. / Abaza, Yasmin; M. Kantarjian, Hagop; Faderl, Stefan; Jabbour, Elias; Jain, Nitin; Thomas, Deborah; Kadia, Tapan; Borthakur, Gautam; D. Khoury, Joseph; Burger, Jan; Wierda, William; O'Brien, Susan; Konopleva, Marina; Ferrajoli, Alessandra; Kebriaei, Partow; Dabaja, Bouthaina; Kornblau, Steven; Alvarado, Yesid; Daver, Naval; Pemmaraju, Naveen; Bose, Prithviraj; Thompson, Philip; Al Azzawi, Hind; Kelly, Mary; Garris, Rebecca; Jain, Preetesh; Garcia-Manero, Guillermo; Cortes, Jorge; Ravandi, Farhad.

In: American Journal of Hematology, Vol. 93, No. 1, 01.2018, p. 91-99.

Research output: Contribution to journalArticle

Abaza, Y, M. Kantarjian, H, Faderl, S, Jabbour, E, Jain, N, Thomas, D, Kadia, T, Borthakur, G, D. Khoury, J, Burger, J, Wierda, W, O'Brien, S, Konopleva, M, Ferrajoli, A, Kebriaei, P, Dabaja, B, Kornblau, S, Alvarado, Y, Daver, N, Pemmaraju, N, Bose, P, Thompson, P, Al Azzawi, H, Kelly, M, Garris, R, Jain, P, Garcia-Manero, G, Cortes, J & Ravandi, F 2018, 'Hyper-CVAD plus nelarabine in newly diagnosed adult T-cell acute lymphoblastic leukemia and T-lymphoblastic lymphoma', American Journal of Hematology, vol. 93, no. 1, pp. 91-99. https://doi.org/10.1002/ajh.24947
Abaza, Yasmin ; M. Kantarjian, Hagop ; Faderl, Stefan ; Jabbour, Elias ; Jain, Nitin ; Thomas, Deborah ; Kadia, Tapan ; Borthakur, Gautam ; D. Khoury, Joseph ; Burger, Jan ; Wierda, William ; O'Brien, Susan ; Konopleva, Marina ; Ferrajoli, Alessandra ; Kebriaei, Partow ; Dabaja, Bouthaina ; Kornblau, Steven ; Alvarado, Yesid ; Daver, Naval ; Pemmaraju, Naveen ; Bose, Prithviraj ; Thompson, Philip ; Al Azzawi, Hind ; Kelly, Mary ; Garris, Rebecca ; Jain, Preetesh ; Garcia-Manero, Guillermo ; Cortes, Jorge ; Ravandi, Farhad. / Hyper-CVAD plus nelarabine in newly diagnosed adult T-cell acute lymphoblastic leukemia and T-lymphoblastic lymphoma. In: American Journal of Hematology. 2018 ; Vol. 93, No. 1. pp. 91-99.
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AU - Abaza, Yasmin

AU - M. Kantarjian, Hagop

AU - Faderl, Stefan

AU - Jabbour, Elias

AU - Jain, Nitin

AU - Thomas, Deborah

AU - Kadia, Tapan

AU - Borthakur, Gautam

AU - D. Khoury, Joseph

AU - Burger, Jan

AU - Wierda, William

AU - O'Brien, Susan

AU - Konopleva, Marina

AU - Ferrajoli, Alessandra

AU - Kebriaei, Partow

AU - Dabaja, Bouthaina

AU - Kornblau, Steven

AU - Alvarado, Yesid

AU - Daver, Naval

AU - Pemmaraju, Naveen

AU - Bose, Prithviraj

AU - Thompson, Philip

AU - Al Azzawi, Hind

AU - Kelly, Mary

AU - Garris, Rebecca

AU - Jain, Preetesh

AU - Garcia-Manero, Guillermo

AU - Cortes, Jorge

AU - Ravandi, Farhad

PY - 2018/1

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N2 - Nelarabine, a water soluble prodrug of 9-β-D-arabinofuranosylguanine (ara-G), is a T-cell specific purine nucleoside analogue. Given its activity in relapsed and refractory T acute lymphoblastic leukemia (T-ALL) and T lymphoblastic lymphoma (T-LBL), we sought to define its role in the frontline treatment of adult patients. Therefore, we conducted a single arm phase 2 study to determine the safety and efficacy of nelarabine in combination with hyper-CVAD in newly diagnosed patients. For induction/consolidation, patients received eight cycles of hyper-CVAD alternating with high-dose methotrexate and cytarabine plus two cycles of nelarabine given at a dose of 650 mg/m2 intravenously daily for 5 days. This was followed by thirty months of POMP maintenance chemotherapy with two additional cycles of nelarabine given instead of cycles 6 and 7 of POMP maintenance. Sixty-seven patients, including 40 with T-ALL and 26 with T-LBL, were enrolled. Complete response rates in both T-ALL and T-LBL were 87% and 100% respectively. Grade 3 to 4 neurotoxic adverse events were reported in 5 patients. There were 21 relapses (31%) including 2 after allogeneic stem cell transplantation. Median duration of follow-up was 42.5 months. The 3-year complete remission duration (CRD) and overall survival (OS) rates were 66% and 65%, respectively. Compared to our historic hyper-CVAD data, there was no survival benefit with the addition of nelarabine. In conclusion, hyper-CVAD plus nelarabine was well tolerated and active in the frontline treatment of adult T-ALL/LBL patients.

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