Nilotinib after imatinib first‐line: a real‐life longitudinal cohort of patients with chronic myeloid leukaemia in chronic phase

• Published in: British journal of haematology 2018-02, Vol.180 (3), p.356-364
• Main Authors: Cony‐Makhoul, Pascale, Gardembas, Martine, Coiteux, Valérie, Carpentier, Nathalie, Pommier, Cécile, Violet, Isabelle, Quittet, Philippe, Berger, Marc G.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Asthenia; BCR‐ABL1; chronic myeloid leukaemia; Chronic myeloid leukemia; Cohort Studies; Drug Resistance, Neoplasm; Female; Fusion Proteins, bcr-abl - genetics; Hematology; Human health and pathology; Humans; Imatinib; Imatinib Mesylate - administration & dosage; Imatinib Mesylate - adverse effects; Imatinib Mesylate - therapeutic use; Intolerance; Leukemia; Leukemia, Myeloid, Chronic-Phase - drug therapy; Leukemia, Myeloid, Chronic-Phase - genetics; Leukemia, Myeloid, Chronic-Phase - mortality; Leukemia, Myeloid, Chronic-Phase - pathology; Life Sciences; Longitudinal Studies; Male; Middle Aged; nilotinib; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Pruritus; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; real‐life practice; Retreatment; second line treatment; Skin; Treatment Outcome
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.15042

Summary This prospective, observational study enrolled 150 adult patients with chronic myeloid leukaemia (CML) in chronic phase (CP) treated with nilotinib as second‐line after imatinib, in a real life setting in France. Two‐thirds of patients switched to nilotinib treatment due to lack of imatinib efficacy. Of 146 evaluable patients, 16 (11·0%) (95% confidence interval: 6·4–17·2%) achieved uMR4, defined as undetectable molecular disease in cDNA with MR4 sensitivity (≥10 000 ABL1 transcripts) at 18 months and confirmed at 24 months (primary endpoint). Among patients without major molecular response (MMR) or deep molecular response (DMR) at study entry, 66·3% achieved MMR and 44·2% DMR within a median of 5·7 and 6·24 months, respectively. Fifty‐three patients (36·3%) have prematurely terminated the study before 24 months of follow‐up, primarily due to nilotinib treatment discontinuation (n = 43; 29·5%), mainly motivated by treatment intolerance (n = 27; 18·5%) and inefficacy (n = 10; 6·8%). The most frequent extra‐haematological adverse events (AEs) reported as related to treatment with nilotinib were pruritus (16·4%), asthenia (13·7%) and dry skin (13·0%). Ischaemic cardiovascular AEs were reported in 18 patients (12·3%). This French nationwide large cohort adds valuable information to the body of evidence on the efficiency and safety of nilotinib in the treatment of patients with CP‐CML.