Dasatinib plus intensive chemotherapy in children, adolescents, and young adults with philadelphia chromosome–positive acute lymphoblastic leukemia

Results of children’s oncology group trial AALL0622

William B. Slayton, Kirk R. Schultz, John A. Kairalla, Meenakshi Devidas, Xinlei Mi, Michael A. Pulsipher, Bill Chang, Charles Mullighan, Ilaria Iacobucci, Lewis B. Silverman, Michael J. Borowitz, Andrew J. Carroll, Nyla A. Heerema, Julie M. Gastier-Foster, Brent L. Wood, Sherri L. Mizrahy, Thomas Merchant, Valerie I. Brown, Lance Sieger, Marilyn J. Siegel & 5 others Elizabeth A. Raetz, Naomi J. Winick, Mignon L. Loh, William L. Carroll, Stephen P. Hunger

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Purpose Addition of imatinib to intensive chemotherapy improved survival for children and young adults with Philadelphia chromosome–positive acute lymphoblastic leukemia. Compared with imatinib, dasatinib has increased potency, CNS penetration, and activity against imatinib-resistant clones. Patients and Methods Children’s Oncology Group (COG) trial AALL0622 (Bristol Myers Squibb trial CA180-204) tested safety and feasibility of adding dasatinib to intensive chemotherapy starting at induction day 15 in patients with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia age 1 to 30 years. Allogeneic hematopoietic stem-cell transplantation (HSCT) was recommended for patients at high risk based on slow response and for those with a matched family donor regardless of response after at least 11 weeks of therapy. Patients at standard risk based on rapid response received chemotherapy plus dasatinib for an additional 120 weeks. Patients with overt CNS leukemia received cranial irradiation. Results Sixty eligible patients were enrolled. Five-year overall (OS) and event-free survival rates (6 standard deviations [SD]) were 86% 6 5% and 60% 6 7% overall, 87% 6 5% and 61% 6 7% for standard-risk patients (n = 48; 19% underwent HSCT), and 89% 6 13% and 67% 6 19% for high-risk patients (n = 9; 89% underwent HSCT), respectively. Five-year cumulative incidence (6 SD) of CNS relapse was 15% 6 6%. Outcomes (6 SDs) were similar to those in COG AALL0031, which used the same chemotherapy with continuous imatinib: 5-year OS of 81% 6 6% versus 86% 6 5% (P = .63) and 5-year disease-free survival of 68% 6 7% versus 60% 6 7% (P = 0.31) for AALL0031 versus AALL0622, respectively. IKZF1 deletions, present in 56% of tested patients, were associated with significantly inferior OS and event-free survival overall and in standard-risk patients. Conclusion Dasatinib was well tolerated with chemotherapy and provided outcomes similar to those with imatinib in COG AALL0031, where all patients received cranial irradiation. Our results support limiting HSCT to slow responders and suggest a potential role for transplantation in rapid responders with IKZF1 deletions.

Original languageEnglish (US)
Pages (from-to)2306-2313
Number of pages8
JournalJournal of Clinical Oncology
Volume36
Issue number22
DOIs
StatePublished - Aug 1 2018

Fingerprint

Precursor Cell Lymphoblastic Leukemia-Lymphoma
Young Adult
Drug Therapy
Hematopoietic Stem Cell Transplantation
Disease-Free Survival
Cranial Irradiation
Dasatinib
Leukemia
Survival Rate
Clone Cells
Transplantation
Imatinib Mesylate
Tissue Donors
Safety
Recurrence
Survival
Incidence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Dasatinib plus intensive chemotherapy in children, adolescents, and young adults with philadelphia chromosome–positive acute lymphoblastic leukemia : Results of children’s oncology group trial AALL0622. / Slayton, William B.; Schultz, Kirk R.; Kairalla, John A.; Devidas, Meenakshi; Mi, Xinlei; Pulsipher, Michael A.; Chang, Bill; Mullighan, Charles; Iacobucci, Ilaria; Silverman, Lewis B.; Borowitz, Michael J.; Carroll, Andrew J.; Heerema, Nyla A.; Gastier-Foster, Julie M.; Wood, Brent L.; Mizrahy, Sherri L.; Merchant, Thomas; Brown, Valerie I.; Sieger, Lance; Siegel, Marilyn J.; Raetz, Elizabeth A.; Winick, Naomi J.; Loh, Mignon L.; Carroll, William L.; Hunger, Stephen P.

In: Journal of Clinical Oncology, Vol. 36, No. 22, 01.08.2018, p. 2306-2313.

Research output: Contribution to journalArticle

Slayton, WB, Schultz, KR, Kairalla, JA, Devidas, M, Mi, X, Pulsipher, MA, Chang, B, Mullighan, C, Iacobucci, I, Silverman, LB, Borowitz, MJ, Carroll, AJ, Heerema, NA, Gastier-Foster, JM, Wood, BL, Mizrahy, SL, Merchant, T, Brown, VI, Sieger, L, Siegel, MJ, Raetz, EA, Winick, NJ, Loh, ML, Carroll, WL & Hunger, SP 2018, 'Dasatinib plus intensive chemotherapy in children, adolescents, and young adults with philadelphia chromosome–positive acute lymphoblastic leukemia: Results of children’s oncology group trial AALL0622', Journal of Clinical Oncology, vol. 36, no. 22, pp. 2306-2313. https://doi.org/10.1200/JCO.2017.76.7228
Slayton, William B. ; Schultz, Kirk R. ; Kairalla, John A. ; Devidas, Meenakshi ; Mi, Xinlei ; Pulsipher, Michael A. ; Chang, Bill ; Mullighan, Charles ; Iacobucci, Ilaria ; Silverman, Lewis B. ; Borowitz, Michael J. ; Carroll, Andrew J. ; Heerema, Nyla A. ; Gastier-Foster, Julie M. ; Wood, Brent L. ; Mizrahy, Sherri L. ; Merchant, Thomas ; Brown, Valerie I. ; Sieger, Lance ; Siegel, Marilyn J. ; Raetz, Elizabeth A. ; Winick, Naomi J. ; Loh, Mignon L. ; Carroll, William L. ; Hunger, Stephen P. / Dasatinib plus intensive chemotherapy in children, adolescents, and young adults with philadelphia chromosome–positive acute lymphoblastic leukemia : Results of children’s oncology group trial AALL0622. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 22. pp. 2306-2313.
@article{3eb37a15aa1240b2b7d0cb6f1a8681ff,
title = "Dasatinib plus intensive chemotherapy in children, adolescents, and young adults with philadelphia chromosome–positive acute lymphoblastic leukemia: Results of children’s oncology group trial AALL0622",
abstract = "Purpose Addition of imatinib to intensive chemotherapy improved survival for children and young adults with Philadelphia chromosome–positive acute lymphoblastic leukemia. Compared with imatinib, dasatinib has increased potency, CNS penetration, and activity against imatinib-resistant clones. Patients and Methods Children’s Oncology Group (COG) trial AALL0622 (Bristol Myers Squibb trial CA180-204) tested safety and feasibility of adding dasatinib to intensive chemotherapy starting at induction day 15 in patients with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia age 1 to 30 years. Allogeneic hematopoietic stem-cell transplantation (HSCT) was recommended for patients at high risk based on slow response and for those with a matched family donor regardless of response after at least 11 weeks of therapy. Patients at standard risk based on rapid response received chemotherapy plus dasatinib for an additional 120 weeks. Patients with overt CNS leukemia received cranial irradiation. Results Sixty eligible patients were enrolled. Five-year overall (OS) and event-free survival rates (6 standard deviations [SD]) were 86{\%} 6 5{\%} and 60{\%} 6 7{\%} overall, 87{\%} 6 5{\%} and 61{\%} 6 7{\%} for standard-risk patients (n = 48; 19{\%} underwent HSCT), and 89{\%} 6 13{\%} and 67{\%} 6 19{\%} for high-risk patients (n = 9; 89{\%} underwent HSCT), respectively. Five-year cumulative incidence (6 SD) of CNS relapse was 15{\%} 6 6{\%}. Outcomes (6 SDs) were similar to those in COG AALL0031, which used the same chemotherapy with continuous imatinib: 5-year OS of 81{\%} 6 6{\%} versus 86{\%} 6 5{\%} (P = .63) and 5-year disease-free survival of 68{\%} 6 7{\%} versus 60{\%} 6 7{\%} (P = 0.31) for AALL0031 versus AALL0622, respectively. IKZF1 deletions, present in 56{\%} of tested patients, were associated with significantly inferior OS and event-free survival overall and in standard-risk patients. Conclusion Dasatinib was well tolerated with chemotherapy and provided outcomes similar to those with imatinib in COG AALL0031, where all patients received cranial irradiation. Our results support limiting HSCT to slow responders and suggest a potential role for transplantation in rapid responders with IKZF1 deletions.",
author = "Slayton, {William B.} and Schultz, {Kirk R.} and Kairalla, {John A.} and Meenakshi Devidas and Xinlei Mi and Pulsipher, {Michael A.} and Bill Chang and Charles Mullighan and Ilaria Iacobucci and Silverman, {Lewis B.} and Borowitz, {Michael J.} and Carroll, {Andrew J.} and Heerema, {Nyla A.} and Gastier-Foster, {Julie M.} and Wood, {Brent L.} and Mizrahy, {Sherri L.} and Thomas Merchant and Brown, {Valerie I.} and Lance Sieger and Siegel, {Marilyn J.} and Raetz, {Elizabeth A.} and Winick, {Naomi J.} and Loh, {Mignon L.} and Carroll, {William L.} and Hunger, {Stephen P.}",
year = "2018",
month = "8",
day = "1",
doi = "10.1200/JCO.2017.76.7228",
language = "English (US)",
volume = "36",
pages = "2306--2313",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "22",

}

TY - JOUR

T1 - Dasatinib plus intensive chemotherapy in children, adolescents, and young adults with philadelphia chromosome–positive acute lymphoblastic leukemia

T2 - Results of children’s oncology group trial AALL0622

AU - Slayton, William B.

AU - Schultz, Kirk R.

AU - Kairalla, John A.

AU - Devidas, Meenakshi

AU - Mi, Xinlei

AU - Pulsipher, Michael A.

AU - Chang, Bill

AU - Mullighan, Charles

AU - Iacobucci, Ilaria

AU - Silverman, Lewis B.

AU - Borowitz, Michael J.

AU - Carroll, Andrew J.

AU - Heerema, Nyla A.

AU - Gastier-Foster, Julie M.

AU - Wood, Brent L.

AU - Mizrahy, Sherri L.

AU - Merchant, Thomas

AU - Brown, Valerie I.

AU - Sieger, Lance

AU - Siegel, Marilyn J.

AU - Raetz, Elizabeth A.

AU - Winick, Naomi J.

AU - Loh, Mignon L.

AU - Carroll, William L.

AU - Hunger, Stephen P.

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Purpose Addition of imatinib to intensive chemotherapy improved survival for children and young adults with Philadelphia chromosome–positive acute lymphoblastic leukemia. Compared with imatinib, dasatinib has increased potency, CNS penetration, and activity against imatinib-resistant clones. Patients and Methods Children’s Oncology Group (COG) trial AALL0622 (Bristol Myers Squibb trial CA180-204) tested safety and feasibility of adding dasatinib to intensive chemotherapy starting at induction day 15 in patients with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia age 1 to 30 years. Allogeneic hematopoietic stem-cell transplantation (HSCT) was recommended for patients at high risk based on slow response and for those with a matched family donor regardless of response after at least 11 weeks of therapy. Patients at standard risk based on rapid response received chemotherapy plus dasatinib for an additional 120 weeks. Patients with overt CNS leukemia received cranial irradiation. Results Sixty eligible patients were enrolled. Five-year overall (OS) and event-free survival rates (6 standard deviations [SD]) were 86% 6 5% and 60% 6 7% overall, 87% 6 5% and 61% 6 7% for standard-risk patients (n = 48; 19% underwent HSCT), and 89% 6 13% and 67% 6 19% for high-risk patients (n = 9; 89% underwent HSCT), respectively. Five-year cumulative incidence (6 SD) of CNS relapse was 15% 6 6%. Outcomes (6 SDs) were similar to those in COG AALL0031, which used the same chemotherapy with continuous imatinib: 5-year OS of 81% 6 6% versus 86% 6 5% (P = .63) and 5-year disease-free survival of 68% 6 7% versus 60% 6 7% (P = 0.31) for AALL0031 versus AALL0622, respectively. IKZF1 deletions, present in 56% of tested patients, were associated with significantly inferior OS and event-free survival overall and in standard-risk patients. Conclusion Dasatinib was well tolerated with chemotherapy and provided outcomes similar to those with imatinib in COG AALL0031, where all patients received cranial irradiation. Our results support limiting HSCT to slow responders and suggest a potential role for transplantation in rapid responders with IKZF1 deletions.

AB - Purpose Addition of imatinib to intensive chemotherapy improved survival for children and young adults with Philadelphia chromosome–positive acute lymphoblastic leukemia. Compared with imatinib, dasatinib has increased potency, CNS penetration, and activity against imatinib-resistant clones. Patients and Methods Children’s Oncology Group (COG) trial AALL0622 (Bristol Myers Squibb trial CA180-204) tested safety and feasibility of adding dasatinib to intensive chemotherapy starting at induction day 15 in patients with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia age 1 to 30 years. Allogeneic hematopoietic stem-cell transplantation (HSCT) was recommended for patients at high risk based on slow response and for those with a matched family donor regardless of response after at least 11 weeks of therapy. Patients at standard risk based on rapid response received chemotherapy plus dasatinib for an additional 120 weeks. Patients with overt CNS leukemia received cranial irradiation. Results Sixty eligible patients were enrolled. Five-year overall (OS) and event-free survival rates (6 standard deviations [SD]) were 86% 6 5% and 60% 6 7% overall, 87% 6 5% and 61% 6 7% for standard-risk patients (n = 48; 19% underwent HSCT), and 89% 6 13% and 67% 6 19% for high-risk patients (n = 9; 89% underwent HSCT), respectively. Five-year cumulative incidence (6 SD) of CNS relapse was 15% 6 6%. Outcomes (6 SDs) were similar to those in COG AALL0031, which used the same chemotherapy with continuous imatinib: 5-year OS of 81% 6 6% versus 86% 6 5% (P = .63) and 5-year disease-free survival of 68% 6 7% versus 60% 6 7% (P = 0.31) for AALL0031 versus AALL0622, respectively. IKZF1 deletions, present in 56% of tested patients, were associated with significantly inferior OS and event-free survival overall and in standard-risk patients. Conclusion Dasatinib was well tolerated with chemotherapy and provided outcomes similar to those with imatinib in COG AALL0031, where all patients received cranial irradiation. Our results support limiting HSCT to slow responders and suggest a potential role for transplantation in rapid responders with IKZF1 deletions.

UR - http://www.scopus.com/inward/record.url?scp=85050744719&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050744719&partnerID=8YFLogxK

U2 - 10.1200/JCO.2017.76.7228

DO - 10.1200/JCO.2017.76.7228

M3 - Article

VL - 36

SP - 2306

EP - 2313

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 22

ER -