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

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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
Issue number7
Publication statusPublished - Jul 2017


  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents
  • Clinical Trial, Phase III
  • Female
  • Fusion Proteins, bcr-abl
  • Humans
  • Journal Article
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
  • Male
  • Middle Aged
  • Multicenter Study
  • Multiplex Polymerase Chain Reaction
  • Philadelphia Chromosome
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Real-Time Polymerase Chain Reaction
  • Young Adult

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