Upfront Combined Hydroxyurea and Imatinib versus Imatinib Monotherapy in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia: A Randomized Controlled Trial

Abstract

Background Tyrosine kinase inhibitors like imatinib have become the cornerstone of therapy in chronic phase-chronic myeloid leukemia (CML-CP). However, the role of hydroxyurea (HU), a deoxyribonucleic acid synthesis inhibitor, has been less explored in the disease. Hence, the present study was conducted to compare the efficacy of structured dose of HU based on baseline total leukocyte count (TLC) with imatinib in CML patients. Method An open-label randomized controlled trial was conducted in 90 newly diagnosed CML-CP patients, aged ≥ 18 years. Patients were randomized to receive either baseline leucocyte count-based structured dose of HU with imatinib or imatinib monotherapy for 3 months. Quantitative real-time polymerase chain reaction for BCR-ABL1 to assess early molecular response (EMR) and safety evaluation according to the Common Terminology Criteria for Adverse Events version 5 was done. Results Median age of patients was 36.5 years (36 [interquartile range [IQR]: 30–45] in I-HU, 38 [IQR: 31–47] in imatinib monotherapy) with male predominance. Fatigue was the most common symptom at diagnosis. Splenomegaly was seen in 89% (median spleen size: 10 [IQR: 6–15] cm). At 3 months, complete hematological response was seen in 74 patients (36 in I-HU, 38 in imatinib monotherapy). Overall, 68 patients achieved EMR (34 in I-HU, 34 in imatinib monotherapy, p = 0.53). The most common hematological toxicity, anemia, was seen in 80 patients (41 in I-HU, 39 in imatinib monotherapy). In 37 patients, nonhematological toxicities seen were nausea and vomiting (20 in I-HU, 17 in imatinib monotherapy). No dose limiting toxicities were reported. Conclusion Addition of upfront TLC-based dosing of HU to imatinib was not found to significantly improve the hematological response and EMR at 3 months. However, long-term studies with a larger sample size with structured dose of HU can be undertaken as it forms a preferred adjunctive therapy for initial, rapid cytoreduction in hyperviscosity or leukostasis-related symptoms in patients of CML.