TKI dose reduction can effectively maintain major molecular remission in patients with chronic myeloid leukaemia

• Published in: British journal of haematology 2021-04, Vol.193 (2), p.346-355
• Main Authors: Claudiani, Simone, Apperley, Jane F., Szydlo, Richard, Khan, Afzal, Nesr, George, Hayden, Chloe, Innes, Andrew, Dominy, Kathy, Foskett, Pierre, Foroni, Letizia, Khorashad, Jamshid, Milojkovic, Dragana
• Format: Article
• Language: English
• Subjects: Adult; Adverse events; Aged; Aged, 80 and over; Aniline Compounds - administration & dosage; Aniline Compounds - adverse effects; Aniline Compounds - therapeutic use; Blast crisis; Chronic myeloid leukemia; CML; Comorbidity; Dasatinib - administration & dosage; Dasatinib - adverse effects; Dasatinib - therapeutic use; dose‐reduction; Drug Tapering - methods; Female; Follow-Up Studies; Fusion Proteins, bcr-abl - genetics; Hematology; Humans; Imatinib Mesylate - administration & dosage; Imatinib Mesylate - adverse effects; Imatinib Mesylate - therapeutic use; Intolerance; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - diagnosis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Life span; low dose; Male; Middle Aged; Mutation; Nitriles - administration & dosage; Nitriles - adverse effects; Nitriles - therapeutic use; Patients; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Quality of Life; Quinolines - administration & dosage; Quinolines - adverse effects; Quinolines - therapeutic use; Remission; Remission Induction - methods; Retrospective Studies; Safety; TFR; TKI; Treatment Outcome; Vigilance
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.17286

Summary Targeted therapy for chronic myeloid leukaemia (CML) has allowed for a near‐normal patient life‐expectancy; however, quality of life and aggravation of existing co‐morbidities have posed new treatment challenges. In clinical practice, TKI dose reduction occurs frequently, often on multiple occasions, because of intolerance. We conducted a retrospective ‘real‐world practice’ review of 246 patients receiving lower than standard dose (LD) TKI after the achievement of major molecular response (MR3), because of intolerable adverse events. In 274 of 298 cases of dose reduction (91·9%), MR3 was maintained at median follow‐up of 27·3 months. One patient progressed to blast crisis while on LD TKI. Two patients developed two new ABL kinase domain mutations (T315I and V299L), of whom one had achieved deep molecular response on an alternative LD TKI at last follow‐up. Seventy‐six patients eventually discontinued LD TKI and the two‐year treatment‐free remission (TFR) rate in these patients was 74·1%. The majority of patients with CML in at least MR3 appear to be safely managed with LD TKI, although three of 246 patients had new events (progression and new mutation), indicating that this approach requires vigilance. TKI LD does not prevent the achievement of TFR in this patient population.