Pakistan journal of medical sciences · 2026
Real world lessons on tyrosine kinase inhibitor response and resistance in CML from a developing country Pakistan.
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Khan Sahrish, Iqbal Zafar, Usman Ghani Muhammad, Farooq Sabar Muhammad
Аннотация
OBJECTIVES: This study aimed to evaluate treatment responses, resistance and molecular characteristics of CML patients on TKI therapies to identify factors associated with suboptimal outcomes.
METHODOLOGY: A retrospective observational study was conducted between January 2022 to December 2025 on 209 CML patients recruited at Mayo Hospital Lahore. Patients who achieved DMR and MMR were included. Minimum required duration of DMR was three years.
RESULTS: A total of 209 patients; 187 (89.4%) were in chronic phase, 12 (5.7%) in accelerated phase, and 10 (4.7%) in blast crisis. The majority were between 30-50 years of age and commonly observed splenomegaly (81.3%) and hepatomegaly (68.4%). Imatinib was prescribed to 114 patients (54.5%); however, 22 required a switch to nilotinib due to resistance.Among CP-CML, 45 (24.0%) patients achieved deep molecular response (DMR) and 18 (9.6%) attained major molecular response (MMR), while one patient from accelerated phase exhibited MMR, leaving more than two-thirds with incomplete responses despite prolonged therapy.Mutation analysis revealed G250E in a blast-phase patient with fatal outcome; another blast case with nilotinib resistance exhibited E459K and expired, E459K in accelerated-phase patient resistant to nilotinib. JAK2 (V617F) in CP-CML/MPN overlap two cases whereas 10 patients remained negative for JAK2 mutation. Death of five out of 10 blast patients have been confirmed.
CONCLUSIONS: These real-world findings highlight the effectiveness of TKI therapy to achieving molecular responses, particularly in a substantial percentage of CP patients. However, variability in treatment response and emerging of resistance-associated mutations in advanced phases, emphasize the personalized management strategy.
METHODOLOGY: A retrospective observational study was conducted between January 2022 to December 2025 on 209 CML patients recruited at Mayo Hospital Lahore. Patients who achieved DMR and MMR were included. Minimum required duration of DMR was three years.
RESULTS: A total of 209 patients; 187 (89.4%) were in chronic phase, 12 (5.7%) in accelerated phase, and 10 (4.7%) in blast crisis. The majority were between 30-50 years of age and commonly observed splenomegaly (81.3%) and hepatomegaly (68.4%). Imatinib was prescribed to 114 patients (54.5%); however, 22 required a switch to nilotinib due to resistance.Among CP-CML, 45 (24.0%) patients achieved deep molecular response (DMR) and 18 (9.6%) attained major molecular response (MMR), while one patient from accelerated phase exhibited MMR, leaving more than two-thirds with incomplete responses despite prolonged therapy.Mutation analysis revealed G250E in a blast-phase patient with fatal outcome; another blast case with nilotinib resistance exhibited E459K and expired, E459K in accelerated-phase patient resistant to nilotinib. JAK2 (V617F) in CP-CML/MPN overlap two cases whereas 10 patients remained negative for JAK2 mutation. Death of five out of 10 blast patients have been confirmed.
CONCLUSIONS: These real-world findings highlight the effectiveness of TKI therapy to achieving molecular responses, particularly in a substantial percentage of CP patients. However, variability in treatment response and emerging of resistance-associated mutations in advanced phases, emphasize the personalized management strategy.