Real-World Data of Molecular Response Using Different Dosage of Upfront Generic Dasatinib in Chronic Phase Chronic Myeloid Leukemia: Single-Center Experience from India

Introduction

The 2^nd 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 >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 <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 <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.

No relevant conflicts of interest to declare.