Nilotinib first-line therapy in patients with Philadelphia chromosome-negative/BCR-ABL-positive chronic myeloid leukemia in chronic phase: ENEST1st sub-analysis

Andreas Hochhaus, Franҫois-Xavier Mahon, Philipp le Coutre, Ljubomir Petrov, Jeroen J W M Janssen, Nicholas C P Cross, Delphine Rea, Fausto Castagnetti, Andrzej Hellmann, Gianantonio Rosti, Norbert Gattermann, Maria Liz Paciello Coronel, Maria Asuncion Echeveste Gutierrez, Valentin Garcia-Gutierrez, Beatrice Vincenzi, Luca Dezzani, Francis J Giles

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

PURPOSE: The ENEST1st sub-analysis presents data based on Philadelphia chromosome (Ph) status, i.e., Ph+ and Ph-/BCR-ABL1 + chronic myeloid leukemia.

METHODS: Patients received nilotinib 300 mg twice daily, up to 24 months.

RESULTS: At screening, 983 patients were identified as Ph+ and 30 patients as Ph-/BCR-ABL + based on cytogenetic and RT-PCR assessment; 76 patients had unknown karyotype (excluded from this sub-analysis). In the Ph-/BCR-ABL1 + subgroup, no additional chromosomal aberrations were reported. In the Ph+ subgroup, 952 patients had safety and molecular assessments. In the Ph-/BCR-ABL1 + subgroup, 30 patients had safety assessments and 28 were followed up for molecular assessments. At 18 months, the molecular response (MR) 4 rate [MR4; BCR-ABL1 ≤0.01% on International Scale (IS)] was similar in the Ph-/BCR-ABL1+ (39.3%) and Ph+ subgroups (38.1%). By 24 months, the cumulative rates of major molecular response (BCR-ABL1IS≤0.1%;), MR4, and MR4.5(BCR-ABL1IS≤0.0032%) were 85.7, 60.7, and 50.0%, respectively, in the Ph-/BCR-ABL1 + subgroup, and 80.3, 54.7, and 38.3%, respectively, in the Ph+ subgroup. In both Ph-/BCR-ABL1 + and Ph+ subgroups, rash (20 and 22%), pruritus (16.7 and 16.7%), nasopharyngitis (13.3 and 10.4%), fatigue (10 and 14.2%), headache (10 and 15.8%), and nausea (6.7 vs 11.4%) were frequent non-hematologic adverse events, whereas hypophosphatemia (23.3 and 6.8%), anemia (10 and 6.5%), and thrombocytopenia (3.3 and 10.2%) were the common hematologic/biochemical laboratory events.

CONCLUSION: Based on similar molecular response and safety results in both subgroups, we conclude that Ph-/BCR-ABL1 + patients benefit from nilotinib in the same way as Ph+ patients.

Original languageEnglish
Pages (from-to)1225-1233
Number of pages9
JournalJournal of Cancer Research and Clinical Oncology
Volume143
Issue number7
DOIs
Publication statusPublished - Jul 2017

Cite this

Hochhaus, Andreas ; Mahon, Franҫois-Xavier ; le Coutre, Philipp ; Petrov, Ljubomir ; Janssen, Jeroen J W M ; Cross, Nicholas C P ; Rea, Delphine ; Castagnetti, Fausto ; Hellmann, Andrzej ; Rosti, Gianantonio ; Gattermann, Norbert ; Coronel, Maria Liz Paciello ; Gutierrez, Maria Asuncion Echeveste ; Garcia-Gutierrez, Valentin ; Vincenzi, Beatrice ; Dezzani, Luca ; Giles, Francis J. / Nilotinib first-line therapy in patients with Philadelphia chromosome-negative/BCR-ABL-positive chronic myeloid leukemia in chronic phase : ENEST1st sub-analysis. In: Journal of Cancer Research and Clinical Oncology. 2017 ; Vol. 143, No. 7. pp. 1225-1233.
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title = "Nilotinib first-line therapy in patients with Philadelphia chromosome-negative/BCR-ABL-positive chronic myeloid leukemia in chronic phase: ENEST1st sub-analysis",
abstract = "PURPOSE: The ENEST1st sub-analysis presents data based on Philadelphia chromosome (Ph) status, i.e., Ph+ and Ph-/BCR-ABL1 + chronic myeloid leukemia.METHODS: Patients received nilotinib 300 mg twice daily, up to 24 months.RESULTS: At screening, 983 patients were identified as Ph+ and 30 patients as Ph-/BCR-ABL + based on cytogenetic and RT-PCR assessment; 76 patients had unknown karyotype (excluded from this sub-analysis). In the Ph-/BCR-ABL1 + subgroup, no additional chromosomal aberrations were reported. In the Ph+ subgroup, 952 patients had safety and molecular assessments. In the Ph-/BCR-ABL1 + subgroup, 30 patients had safety assessments and 28 were followed up for molecular assessments. At 18 months, the molecular response (MR) 4 rate [MR4; BCR-ABL1 ≤0.01{\%} on International Scale (IS)] was similar in the Ph-/BCR-ABL1+ (39.3{\%}) and Ph+ subgroups (38.1{\%}). By 24 months, the cumulative rates of major molecular response (BCR-ABL1IS≤0.1{\%};), MR4, and MR4.5(BCR-ABL1IS≤0.0032{\%}) were 85.7, 60.7, and 50.0{\%}, respectively, in the Ph-/BCR-ABL1 + subgroup, and 80.3, 54.7, and 38.3{\%}, respectively, in the Ph+ subgroup. In both Ph-/BCR-ABL1 + and Ph+ subgroups, rash (20 and 22{\%}), pruritus (16.7 and 16.7{\%}), nasopharyngitis (13.3 and 10.4{\%}), fatigue (10 and 14.2{\%}), headache (10 and 15.8{\%}), and nausea (6.7 vs 11.4{\%}) were frequent non-hematologic adverse events, whereas hypophosphatemia (23.3 and 6.8{\%}), anemia (10 and 6.5{\%}), and thrombocytopenia (3.3 and 10.2{\%}) were the common hematologic/biochemical laboratory events.CONCLUSION: Based on similar molecular response and safety results in both subgroups, we conclude that Ph-/BCR-ABL1 + patients benefit from nilotinib in the same way as Ph+ patients.",
keywords = "Adolescent, Adult, Aged, Antineoplastic Agents, Female, Fusion Proteins, bcr-abl, Humans, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Male, Middle Aged, Multiplex Polymerase Chain Reaction, Philadelphia Chromosome, Protein Kinase Inhibitors, Pyrimidines, Real-Time Polymerase Chain Reaction, Young Adult, Clinical Trial, Phase III, Journal Article, Multicenter Study",
author = "Andreas Hochhaus and Franҫois-Xavier Mahon and {le Coutre}, Philipp and Ljubomir Petrov and Janssen, {Jeroen J W M} and Cross, {Nicholas C P} and Delphine Rea and Fausto Castagnetti and Andrzej Hellmann and Gianantonio Rosti and Norbert Gattermann and Coronel, {Maria Liz Paciello} and Gutierrez, {Maria Asuncion Echeveste} and Valentin Garcia-Gutierrez and Beatrice Vincenzi and Luca Dezzani and Giles, {Francis J}",
year = "2017",
month = "7",
doi = "10.1007/s00432-017-2359-9",
language = "English",
volume = "143",
pages = "1225--1233",
journal = "Journal of Cancer Research and Clinical Oncology",
issn = "0171-5216",
publisher = "Springer Verlag",
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}

Hochhaus, A, Mahon, F-X, le Coutre, P, Petrov, L, Janssen, JJWM, Cross, NCP, Rea, D, Castagnetti, F, Hellmann, A, Rosti, G, Gattermann, N, Coronel, MLP, Gutierrez, MAE, Garcia-Gutierrez, V, Vincenzi, B, Dezzani, L & Giles, FJ 2017, 'Nilotinib first-line therapy in patients with Philadelphia chromosome-negative/BCR-ABL-positive chronic myeloid leukemia in chronic phase: ENEST1st sub-analysis' Journal of Cancer Research and Clinical Oncology, vol. 143, no. 7, pp. 1225-1233. https://doi.org/10.1007/s00432-017-2359-9

Nilotinib first-line therapy in patients with Philadelphia chromosome-negative/BCR-ABL-positive chronic myeloid leukemia in chronic phase : ENEST1st sub-analysis. / Hochhaus, Andreas; Mahon, Franҫois-Xavier; le Coutre, Philipp; Petrov, Ljubomir; Janssen, Jeroen J W M; Cross, Nicholas C P; Rea, Delphine; Castagnetti, Fausto; Hellmann, Andrzej; Rosti, Gianantonio; Gattermann, Norbert; Coronel, Maria Liz Paciello; Gutierrez, Maria Asuncion Echeveste; Garcia-Gutierrez, Valentin; Vincenzi, Beatrice; Dezzani, Luca; Giles, Francis J.

In: Journal of Cancer Research and Clinical Oncology, Vol. 143, No. 7, 07.2017, p. 1225-1233.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Nilotinib first-line therapy in patients with Philadelphia chromosome-negative/BCR-ABL-positive chronic myeloid leukemia in chronic phase

T2 - ENEST1st sub-analysis

AU - Hochhaus, Andreas

AU - Mahon, Franҫois-Xavier

AU - le Coutre, Philipp

AU - Petrov, Ljubomir

AU - Janssen, Jeroen J W M

AU - Cross, Nicholas C P

AU - Rea, Delphine

AU - Castagnetti, Fausto

AU - Hellmann, Andrzej

AU - Rosti, Gianantonio

AU - Gattermann, Norbert

AU - Coronel, Maria Liz Paciello

AU - Gutierrez, Maria Asuncion Echeveste

AU - Garcia-Gutierrez, Valentin

AU - Vincenzi, Beatrice

AU - Dezzani, Luca

AU - Giles, Francis J

PY - 2017/7

Y1 - 2017/7

N2 - PURPOSE: The ENEST1st sub-analysis presents data based on Philadelphia chromosome (Ph) status, i.e., Ph+ and Ph-/BCR-ABL1 + chronic myeloid leukemia.METHODS: Patients received nilotinib 300 mg twice daily, up to 24 months.RESULTS: At screening, 983 patients were identified as Ph+ and 30 patients as Ph-/BCR-ABL + based on cytogenetic and RT-PCR assessment; 76 patients had unknown karyotype (excluded from this sub-analysis). In the Ph-/BCR-ABL1 + subgroup, no additional chromosomal aberrations were reported. In the Ph+ subgroup, 952 patients had safety and molecular assessments. In the Ph-/BCR-ABL1 + subgroup, 30 patients had safety assessments and 28 were followed up for molecular assessments. At 18 months, the molecular response (MR) 4 rate [MR4; BCR-ABL1 ≤0.01% on International Scale (IS)] was similar in the Ph-/BCR-ABL1+ (39.3%) and Ph+ subgroups (38.1%). By 24 months, the cumulative rates of major molecular response (BCR-ABL1IS≤0.1%;), MR4, and MR4.5(BCR-ABL1IS≤0.0032%) were 85.7, 60.7, and 50.0%, respectively, in the Ph-/BCR-ABL1 + subgroup, and 80.3, 54.7, and 38.3%, respectively, in the Ph+ subgroup. In both Ph-/BCR-ABL1 + and Ph+ subgroups, rash (20 and 22%), pruritus (16.7 and 16.7%), nasopharyngitis (13.3 and 10.4%), fatigue (10 and 14.2%), headache (10 and 15.8%), and nausea (6.7 vs 11.4%) were frequent non-hematologic adverse events, whereas hypophosphatemia (23.3 and 6.8%), anemia (10 and 6.5%), and thrombocytopenia (3.3 and 10.2%) were the common hematologic/biochemical laboratory events.CONCLUSION: Based on similar molecular response and safety results in both subgroups, we conclude that Ph-/BCR-ABL1 + patients benefit from nilotinib in the same way as Ph+ patients.

AB - PURPOSE: The ENEST1st sub-analysis presents data based on Philadelphia chromosome (Ph) status, i.e., Ph+ and Ph-/BCR-ABL1 + chronic myeloid leukemia.METHODS: Patients received nilotinib 300 mg twice daily, up to 24 months.RESULTS: At screening, 983 patients were identified as Ph+ and 30 patients as Ph-/BCR-ABL + based on cytogenetic and RT-PCR assessment; 76 patients had unknown karyotype (excluded from this sub-analysis). In the Ph-/BCR-ABL1 + subgroup, no additional chromosomal aberrations were reported. In the Ph+ subgroup, 952 patients had safety and molecular assessments. In the Ph-/BCR-ABL1 + subgroup, 30 patients had safety assessments and 28 were followed up for molecular assessments. At 18 months, the molecular response (MR) 4 rate [MR4; BCR-ABL1 ≤0.01% on International Scale (IS)] was similar in the Ph-/BCR-ABL1+ (39.3%) and Ph+ subgroups (38.1%). By 24 months, the cumulative rates of major molecular response (BCR-ABL1IS≤0.1%;), MR4, and MR4.5(BCR-ABL1IS≤0.0032%) were 85.7, 60.7, and 50.0%, respectively, in the Ph-/BCR-ABL1 + subgroup, and 80.3, 54.7, and 38.3%, respectively, in the Ph+ subgroup. In both Ph-/BCR-ABL1 + and Ph+ subgroups, rash (20 and 22%), pruritus (16.7 and 16.7%), nasopharyngitis (13.3 and 10.4%), fatigue (10 and 14.2%), headache (10 and 15.8%), and nausea (6.7 vs 11.4%) were frequent non-hematologic adverse events, whereas hypophosphatemia (23.3 and 6.8%), anemia (10 and 6.5%), and thrombocytopenia (3.3 and 10.2%) were the common hematologic/biochemical laboratory events.CONCLUSION: Based on similar molecular response and safety results in both subgroups, we conclude that Ph-/BCR-ABL1 + patients benefit from nilotinib in the same way as Ph+ patients.

KW - Adolescent

KW - Adult

KW - Aged

KW - Antineoplastic Agents

KW - Female

KW - Fusion Proteins, bcr-abl

KW - Humans

KW - Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative

KW - Male

KW - Middle Aged

KW - Multiplex Polymerase Chain Reaction

KW - Philadelphia Chromosome

KW - Protein Kinase Inhibitors

KW - Pyrimidines

KW - Real-Time Polymerase Chain Reaction

KW - Young Adult

KW - Clinical Trial, Phase III

KW - Journal Article

KW - Multicenter Study

U2 - 10.1007/s00432-017-2359-9

DO - 10.1007/s00432-017-2359-9

M3 - Article

VL - 143

SP - 1225

EP - 1233

JO - Journal of Cancer Research and Clinical Oncology

JF - Journal of Cancer Research and Clinical Oncology

SN - 0171-5216

IS - 7

ER -