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

• Published in: Journal of cancer research and clinical oncology Vol. 143; no. 7; pp. 1225 - 1233
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-07-2017; Springer Nature B.V
• Subjects: Abl protein; Adolescent; Adult; Aged; Anemia; Antineoplastic Agents - therapeutic use; BCR protein; Cancer Research; Chemotherapy; Chromosome aberrations; Chromosomes; Chronic myeloid leukemia; Clinical outcomes; Data processing; Exanthema; Fatigue; Female; Fusion protein; Fusion Proteins, bcr-abl - genetics; Headache; Hematology; Humans; Hypophosphatemia; Internal Medicine; Leukemia; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative - drug therapy; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative - genetics; Male; Medicine; Medicine & Public Health; Middle Aged; Multiplex Polymerase Chain Reaction; Myeloid leukemia; Nausea; Oncology; Original Article – Clinical Oncology; Original – Clinical Oncology; Philadelphia Chromosome; Polymerase chain reaction; Protein Kinase Inhibitors - therapeutic use; Pruritus; Pyrimidines - therapeutic use; Real-Time Polymerase Chain Reaction; Rhinopharyngitis; Targeted cancer therapy; Thrombocytopenia; Young Adult; Nilotinib; ENEST1st; Chronic myeloid leukemia; Philadelphia chromosome negative/BCR-ABL positive
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-017-2359-9

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 [MR
4
; 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-ABL1
IS
≤0.1%;), MR
4
, and MR
4.5
(BCR-ABL1
IS
≤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.