Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia

Adult Acute Lymphoblastic Leukemia Working Party of the Korean Society of Hematology

Research output: Contribution to journalArticle

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Abstract

We investigated the effects of nilotinib plus multiagent chemotherapy, followed by consolidation/maintenance or allogeneic hematopoietic cell transplantation (allo-HCT) for adult patients with newly diagnosed Philadelphia-positive (Ph-pos) acute lymphoblastic leukemia (ALL). Study subjects received induction treatment that comprised concurrent vincristine, daunorubicin, prednisolone, and nilotinib. After achieving complete hematologic remission (HCR), subjects received either 5 courses of consolidation, followed by 2-year maintenance with nilotinib, or allo-HCT. Minimal residual disease (MRD) was assessed at HCR, and every 3 months thereafter. The molecular responses (MRs) were defined as MR3 for BCR-ABL1/G6PDH ratios ≤10-3 and MR5 for ratios <10-5. Ninety evaluable subjects, ages 17 to 71 years, were enrolled in 17 centers. The HCR rate was 91%; 57 subjects received allo-HCT. The cumulative MR5 rate was 94%; the 2-year hematologic relapse-free survival (HRFS) rate was 72% for 82 subjects that achieved HCR, and the 2-year overall survival rate was 72%. Subjects that failed to achieve MR3 or MR5 were 9.1 times (P = .004) or 6.3 times (P = .001) more prone to hematologic relapse, respectively, than those that achieved MR3 or MR5. MRD statuses just before allo-HCT and at 3 months after allo-HCT were predictive of 2-year HRFS. Adverse events occurred mainly during induction, and most were reversible with dose reduction or transient interruption of nilotinib. The combination of nilotinib with high-dose cytotoxic drugs was feasible, and it effectively achieved high cumulative complete molecular remission and HRFS rates. The MRD status at early postremission time was predictive of the HRFS. This trial was registered at www.clinicaltrials.gov as #NCT00844298.

Original languageEnglish
Pages (from-to)746-756
Number of pages11
JournalBlood
Volume126
Issue number6
DOIs
Publication statusPublished - 2015 Aug 6

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Chemotherapy
Cell Transplantation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Residual Neoplasm
Recurrence
Drug Therapy
Consolidation
Survival Rate
Consolidation Chemotherapy
Maintenance
Daunorubicin
Vincristine
Prednisolone
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
Survival
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology
  • Medicine(all)

Cite this

Adult Acute Lymphoblastic Leukemia Working Party of the Korean Society of Hematology (2015). Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Blood, 126(6), 746-756. https://doi.org/10.1182/blood-2015-03-636548

Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. / Adult Acute Lymphoblastic Leukemia Working Party of the Korean Society of Hematology.

In: Blood, Vol. 126, No. 6, 06.08.2015, p. 746-756.

Research output: Contribution to journalArticle

Adult Acute Lymphoblastic Leukemia Working Party of the Korean Society of Hematology 2015, 'Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia', Blood, vol. 126, no. 6, pp. 746-756. https://doi.org/10.1182/blood-2015-03-636548
Adult Acute Lymphoblastic Leukemia Working Party of the Korean Society of Hematology. Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Blood. 2015 Aug 6;126(6):746-756. https://doi.org/10.1182/blood-2015-03-636548
Adult Acute Lymphoblastic Leukemia Working Party of the Korean Society of Hematology. / Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. In: Blood. 2015 ; Vol. 126, No. 6. pp. 746-756.
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AU - Adult Acute Lymphoblastic Leukemia Working Party of the Korean Society of Hematology

AU - Kim, Dae Young

AU - Joo, Young Don

AU - Lim, Sung Nam

AU - Kim, Sung Doo

AU - Lee, Jung Hee

AU - Lee, Je Hwan

AU - Kim, Dong Hwan

AU - Kim, Kihyun

AU - Jung, Chul Won

AU - Kim, Inho

AU - Yoon, Sung Soo

AU - Park, Seonyang

AU - Ahn, Jae Sook

AU - Yang, Deok Hwan

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AU - Lee, Ho Sup

AU - Kim, Yang Soo

AU - Mun, Yeung Chul

AU - Kim, Hawk

AU - Park, Jae Hoo

AU - Moon, Joon Ho

AU - Sohn, Sang Kyun

AU - Lee, Sang Min

AU - Lee, Won Sik

AU - Kim, Kyoung Ha

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AU - Lee, Hyewon

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AU - Lee, Gyeong Won

AU - Cho, Young Uk

AU - Jang, Seongsoo

AU - Park, Chan Jeoung

AU - Chi, Hyun Sook

AU - Lee, Kyoo Hyung

AU - Kim, Byoung Kook

AU - Yoon, Whi Hoong

AU - Cho, Kyung Sam

AU - Min, Yoo Hong

AU - Lee, Hong Ghi

AU - Kim, Chul Soo

AU - Kim, Hyeoung Joon

AU - Kim, Byung Soo

AU - Jo, Deog Yeon

AU - Choi, Chul Won

AU - Park, Yong

PY - 2015/8/6

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N2 - We investigated the effects of nilotinib plus multiagent chemotherapy, followed by consolidation/maintenance or allogeneic hematopoietic cell transplantation (allo-HCT) for adult patients with newly diagnosed Philadelphia-positive (Ph-pos) acute lymphoblastic leukemia (ALL). Study subjects received induction treatment that comprised concurrent vincristine, daunorubicin, prednisolone, and nilotinib. After achieving complete hematologic remission (HCR), subjects received either 5 courses of consolidation, followed by 2-year maintenance with nilotinib, or allo-HCT. Minimal residual disease (MRD) was assessed at HCR, and every 3 months thereafter. The molecular responses (MRs) were defined as MR3 for BCR-ABL1/G6PDH ratios ≤10-3 and MR5 for ratios <10-5. Ninety evaluable subjects, ages 17 to 71 years, were enrolled in 17 centers. The HCR rate was 91%; 57 subjects received allo-HCT. The cumulative MR5 rate was 94%; the 2-year hematologic relapse-free survival (HRFS) rate was 72% for 82 subjects that achieved HCR, and the 2-year overall survival rate was 72%. Subjects that failed to achieve MR3 or MR5 were 9.1 times (P = .004) or 6.3 times (P = .001) more prone to hematologic relapse, respectively, than those that achieved MR3 or MR5. MRD statuses just before allo-HCT and at 3 months after allo-HCT were predictive of 2-year HRFS. Adverse events occurred mainly during induction, and most were reversible with dose reduction or transient interruption of nilotinib. The combination of nilotinib with high-dose cytotoxic drugs was feasible, and it effectively achieved high cumulative complete molecular remission and HRFS rates. The MRD status at early postremission time was predictive of the HRFS. This trial was registered at www.clinicaltrials.gov as #NCT00844298.

AB - We investigated the effects of nilotinib plus multiagent chemotherapy, followed by consolidation/maintenance or allogeneic hematopoietic cell transplantation (allo-HCT) for adult patients with newly diagnosed Philadelphia-positive (Ph-pos) acute lymphoblastic leukemia (ALL). Study subjects received induction treatment that comprised concurrent vincristine, daunorubicin, prednisolone, and nilotinib. After achieving complete hematologic remission (HCR), subjects received either 5 courses of consolidation, followed by 2-year maintenance with nilotinib, or allo-HCT. Minimal residual disease (MRD) was assessed at HCR, and every 3 months thereafter. The molecular responses (MRs) were defined as MR3 for BCR-ABL1/G6PDH ratios ≤10-3 and MR5 for ratios <10-5. Ninety evaluable subjects, ages 17 to 71 years, were enrolled in 17 centers. The HCR rate was 91%; 57 subjects received allo-HCT. The cumulative MR5 rate was 94%; the 2-year hematologic relapse-free survival (HRFS) rate was 72% for 82 subjects that achieved HCR, and the 2-year overall survival rate was 72%. Subjects that failed to achieve MR3 or MR5 were 9.1 times (P = .004) or 6.3 times (P = .001) more prone to hematologic relapse, respectively, than those that achieved MR3 or MR5. MRD statuses just before allo-HCT and at 3 months after allo-HCT were predictive of 2-year HRFS. Adverse events occurred mainly during induction, and most were reversible with dose reduction or transient interruption of nilotinib. The combination of nilotinib with high-dose cytotoxic drugs was feasible, and it effectively achieved high cumulative complete molecular remission and HRFS rates. The MRD status at early postremission time was predictive of the HRFS. This trial was registered at www.clinicaltrials.gov as #NCT00844298.

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