Real-World Data of Molecular Response Using Different Dosage of Upfront Generic Dasatinib in Chronic Phase Chronic Myeloid Leukemia: Single-Center Experience from India
Authors: Satadeve Paras , Singh Sashi , Gupta Adamya , Kachhwaha Arjun , Benson Reshma , Kumar Karthik , Nayak Jhasaketan , Ronanki Kavya , Shah Bibhant , Dalton Prisla , Nagpal Nikhil , Nath Uttam Kumar 
Published: December 2024

Introduction
The 2nd generation tyrosine kinase inhibitor (TKI) agent dasatinib is approved for upfront therapy in newly diagnosed chronic phase chronic myeloid leukemia (CML-CP) patients. The recommended dasatinib dose of 100mg/day is frequently associated with several dose-limiting adverse effects. There is limited data on efficacy & safety of lower doses of dasatinib (50-70 mg/day). The availability of generic dasatinib preparation in India has increased upfront use in CML-CP patients. The present single-center, observational study from India describes treatment results & adverse events profile of different doses of generic dasatinib.
Aims To study complete hematological response (CHR), early molecular response (EMR), major molecular response (MMR) and deep molecular response (DMR) in newly diagnosed CML-CP patients treated with dasatinib doses of 70mg & 100mg/day. To analyse the adverse events (AEs) of different doses of generic dasatinib.
Method
We retrospectively analysed the data of all newly diagnosed CML-CP patients of &gt;12 years of age who were treated with upfront generic formulation of dasatinib at different doses (70mg & 100mg/day) at our center between January 2021 to march 2024. CML-CP patients with significant cardiac comorbidities were considered ineligible for dasatinib. Patients were stringently monitored for treatment response & adverse events at defined intervals. Response rates and adverse events were defined as per ELN 2020 recommendations & NCI-CTCAE v-5 respectively.
Result
Out of total 164 treatment naïve CML-CP patients who were assessed for eligibility for upfront dasatinib,150 patients were started on dasatinib therapy. Of these hematological & molecular response data of 139 patients are available, as 11 patients were lost to follow up before completing at least 3 months of therapy. The median age of patients was 43 years (range 12-72), with male: female ratio of 1.3:1. The percentage of patients who received dasatinib 70mg & 100mg dose was 32% (n=44) & 68% (n=95) respectively. After 3 months of therapy, CHR was achieved in overall 96% patients (98% with dasatinib 70 mg & 96% with dasatinib 100 mg dose). Early molecular response (BCR-ABL1 &lt;10%, I.S) was achieved in overall 92% patients (92% with dasatinib 70 mg & 93% with dasatinib 100 mg dose). After 12 months of therapy, MMR (BCR-ABL1 &lt;0.1%, I.S) was achieved in overall 89% patients (88% with dasatinib 70 mg dose & 90% with dasatinib 100 mg dose). Deep molecular response (MR4.0 & MR4.5) was achieved in overall 59% & 26% patients respectively. One patient who received dasatinib 100 mg dose experienced treatment failure due to T315I mutation & was switched to an alternative TKI agent.
The common hematological AEs of any grade were neutropenia (33%), anemia (29%), thrombocytopenia (27%), & common non-hematological AEs were diarrhea (36%), nausea (14%), & vomiting (10%). Pleural effusion (grade 1-2) occurred in 7% patients. The commonest grade ≥3 AEs were diarrhea (16%) and thrombocytopenia (10%). Dasatinib dose reduction/interruption was required for grade 3 diarrhea in 16% patients & for pleural effusion in 8% patients. Three patients (2%) required permanent discontinuation of dasatinib due to recurrent pleural effusion. One patient with TKI-induced severe myelosuppression died of sepsis. At median follow up of 14 months, 134 patients are continuing the treatment.
Conclusion
Our single-center experience suggests that generic dasatinib is effective & well tolerated in Indian CML-CP patients, & is beneficial in reducing financial burden & increasing compliance in severely resource-constrained settings. Efficacy & safety of generic dasatinib is comparable with original study data.