Early Results of comparison of low-dose generic dasatinib (50 MG/Day) versus imatinib (400 MG/Day) in newly diagnosed chronic Phase chronic myeloid leukemia: Real-world evidence from a single-center, randomized controlled study from India

Abstract

Abstract Background:Chronic myeloid leukemia is one of the most prevalent leukemias in the adult Indian population. Imatinib remains the TKI of choice due to its affordability & acceptable safety profile. Dasatinib has demonstrated superiority over imatinib in terms of achieving early & durable deep molecular responses, although it is associated with several dose-limiting adverse events. Availability of a generic formulation of dasatinib in India has encouraged its upfront use in CML-CP patients. Anecdotal evidence suggests that lower doses of dasatinib may retain efficacy while reducing toxicity. However, there is a scarcity of data comparing the efficacy & safety of low-dose generic dasatinib (50 mg) to generic imatinib (400 mg) in CML-CP patients. The present study aims to address this gap through a single-center, randomized trial conducted at a tertiary care hospital in India. Aims: To compare the rates of Complete Hematological Response (CHR), Early Molecular Response (EMR, BCR-ABL1 ≤ 10% IS), Complete Cytogenetic Remission (CCyR, BCR-ABL1 ≤ 1% IS), and Major Molecular Response (MMR, BCR-ABL1 ≤ 0.1% IS) at 3 and 6 months of therapy in patients treated with low-dose generic dasatinib (50 mg/day) versus generic imatinib (400 mg/day). To compare the adverse events (AEs) in the two treatment groups. Method:The present study enrolled newly diagnosed CML-CP patients of ≥ 18 years of age between February 2024 & March 2025. Eligible subjects were randomized to receive either generic formulations of dasatinib at 50 mg/day or a generic formulation of imatinib at 400 mg/day, with strict monitoring of treatment responses and adverse events at defined intervals. Response rates and adverse events were defined as per ELN 2020 recommendations & NCI-CTCAE V-5, respectively. Results: Out of 67 consecutively screened treatment-naïve CML patients, 58 patients with a confirmed diagnosis of chronic phase CML [dasatinib 50 mg (n)=29, imatinib 400 mg (n)=29] completed at least 6 months of therapy & were included in the efficacy & safety analysis. The median age of patients was 44 years (range 18-69), with a male-to-female ratio of 1.8:1. ELTS risk categories included low (22%), intermediate (45%), & high (33%). At 3 months, 54 of 58 patients (93%) achieved complete hematologic response (CHR). Early molecular response (EMR) rates at 3 months were 86% in the dasatinib group and 82% in the imatinib group. At 6 months, the rates of EMR, complete cytogenetic response (CCyR), and major molecular response (MMR) for dasatinib versus imatinib were as follows: EMR-86% vs. 82%; CCyR-65% vs. 52%; and MMR-38% vs. 24%, respectively. In ELTS intermediate- and high-risk groups, CCyR and MMR rates were 61% and 31% in the dasatinib group, compared to 50% and 23% in the imatinib group. Although molecular response rates were numerically higher in the dasatinib group, the differences were not statistically significant. Both the generic dasatinib (50 mg) and imatinib (400 mg) were generally well tolerated. Gastrointestinal & hematological toxicities (e.g., diarrhea, cytopenia) were more common in the dasatinib group, whereas musculoskeletal symptoms (e.g., myalgia, arthralgia) predominated in the imatinib group. However, the incidence of grade 3-4 adverse events was not significantly different. Notably, any grade adverse events leading to dose reduction or interruption were significantly lower in the dasatinib group (7%) compared to the imatinib group (28%) (P=0.037). At the time of analysis, one patient in the dasatinib group progressed to the blast phase, and another died from febrile neutropenia secondary to bone marrow aplasia. Conclusion: This single-center study suggests that a low dose of a generic formulation of dasatinib (50 mg/day) is well tolerated and associated with improved early and deeper molecular response rates compared to imatinib (400 mg/day), particularly in intermediate- to high-risk ELTS scores. It also offers potential advantages in terms of affordability & treatment compliance in resource-constrained settings.