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.

• Authors: 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
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 143 Issue 7 Pg. 1225-1233 (Jul 2017) ISSN: 1432-1335 [Electronic] Germany
• PMID: 28224300 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study)

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• Pyrimidines
• Fusion Proteins, bcr-abl
• nilotinib

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Agents (therapeutic use)
• Female
• Fusion Proteins, bcr-abl (genetics)
• Humans
• Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative (drug therapy, genetics)
• Male
• Middle Aged
• Multiplex Polymerase Chain Reaction
• Philadelphia Chromosome
• Protein Kinase Inhibitors (therapeutic use)
• Pyrimidines (therapeutic use)
• Real-Time Polymerase Chain Reaction
• Young Adult