Purpose: The ENEST1st sub-analysis presents data based on Philadelphia chromosome (Ph) status, i.e., Ph+ and Phâ/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 Phâ/BCR-ABL + based on cytogenetic and RT-PCR assessment; 76 patients had unknown karyotype (excluded from this sub-analysis). In the Phâ/BCR-ABL1 + subgroup, no additional chromosomal aberrations were reported. In the Ph+ subgroup, 952 patients had safety and molecular assessments. In the Phâ/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 â¤0.01% on International Scale (IS)] was similar in the Phâ/BCR-ABL1+ (39.3%) and Ph+ subgroups (38.1%). By 24 months, the cumulative rates of major molecular response (BCR-ABL1ISâ¤0.1%;), MR4, and MR4.5(BCR-ABL1ISâ¤0.0032%) were 85.7, 60.7, and 50.0%, respectively, in the Phâ/BCR-ABL1 + subgroup, and 80.3, 54.7, and 38.3%, respectively, in the Ph+ subgroup. In both Phâ/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 Phâ/BCR-ABL1 + patients benefit from nilotinib in the same way as Ph+ patients.
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, Franois-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. - ISSN 0171-5216. - STAMPA. - 143:7(2017), pp. 1225-1233. [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
Castagnetti, Fausto;Rosti, Gianantonio;
2017
Abstract
Purpose: The ENEST1st sub-analysis presents data based on Philadelphia chromosome (Ph) status, i.e., Ph+ and Phâ/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 Phâ/BCR-ABL + based on cytogenetic and RT-PCR assessment; 76 patients had unknown karyotype (excluded from this sub-analysis). In the Phâ/BCR-ABL1 + subgroup, no additional chromosomal aberrations were reported. In the Ph+ subgroup, 952 patients had safety and molecular assessments. In the Phâ/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 â¤0.01% on International Scale (IS)] was similar in the Phâ/BCR-ABL1+ (39.3%) and Ph+ subgroups (38.1%). By 24 months, the cumulative rates of major molecular response (BCR-ABL1ISâ¤0.1%;), MR4, and MR4.5(BCR-ABL1ISâ¤0.0032%) were 85.7, 60.7, and 50.0%, respectively, in the Phâ/BCR-ABL1 + subgroup, and 80.3, 54.7, and 38.3%, respectively, in the Ph+ subgroup. In both Phâ/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 Phâ/BCR-ABL1 + patients benefit from nilotinib in the same way as Ph+ patients.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.