An Observational Prospective Study of Dasatinib 50mg Daily As Frontline Therapy in Newly Diagnosed Chronic Myeloid Leukemia Patients in Chronic Phase

Study Title: An observational prospective study of Dasatinib 50mg Daily as Frontline Therapy in newly diagnosed Chronic Myeloid Leukemia patients in Chronic Phase

Background:

BCR-ABL Tyrosine kinase inhibitors (TKI's) are most successful of targeted therapies and are currently considered cornerstone in the management of patients with chronic myeloid leukemia (CML). TKIs approved for first line therapy in CML are Imatinib, Nilotinib, Dasatinib and Bosutinib. Data suggests that Dasatinib, a second generation TKI is 325 times more potent than Imatinib. [1, 2] A five-year follow-up of DASISION study showed that Dasatinib 100mg as a frontline lead to more rapid and deeper responses at early time points when compared with Imatinib, with estimated 5 years OS & PFS as 91% and 85%, also 5-year MMR rate as 76% respectively. [3]

Talpaz. M. et al study showed that Dasatinib is active in lower dose and have better safety profile when evaluated as a second line treatment after Imatinib failure. [4] Naqvi et al. results showed that Dasatinib 50mg is active and well tolerated and also have the better 3- and 6-month rate of molecular response (BCR-ABL1 transcripts (IS) ≤1%) i.e., 72% and 84%, compared with 48% and 69% with Dasatinib 100mg, and 13% and 49% with imatinib 400mg, respectively. [5, 6]. Therefore, we aim to evaluate the molecular responses and safety of Dasatinib 50mg daily as a frontline therapy in Indian CML-CP patients.

Material & Methods:

It is an observational prospective study. All CML-CP patients started on Dasatinib 50mg daily will be offered to participate in this study. The data of demography, baseline characteristics, molecular response, toxicity, deaths, progression will be collected and the same will be entered in case record form/excel sheet. We retrospectively collected the data of Imatinib to compare the response outcome with lower dose dasatinib 50mg daily. Patients who received frontline dasatinib 50mg for less than 3 months for reasons other than toxic effects or intolerance to dasatinib were discontinued from the study. Informed consent form has been taken from patients who participated in the study.

Objectives:

• To evaluate and compare the efficacy of lower dose dasatinib 50mg daily and Imatinib in Indian patients with CML-CP.

• To assess toxicities of lower dose dasatinib 50mg daily according to the CTCAE v 5.0

Results:

Between June 2020 to Feb 2022, total 50 patients were included in the dasatinib 50mg once daily. Median age is 40 yrs. ranging from (19-73) yrs. Median spleen and liver size is 8cm (2 - 22) cm and 2cm (0 - 16.8) cm respectively. Duration of symptoms are 60 days (4 - 547) days. Median Hb, TLC and Platelets are 10.25gm/dL (5.1 - 14.9) gm/dL, 158980/cumm (30400 - 572880)/cumm and 327 × 10⁹/L (83 - 789) × 10⁹/L. Median time from diagnosis to treatment was 6 days (0 - 20) days. At a median follow up of 9.2 months, 49 patients completed 3 months and out of which 48 patients were evaluated as one patient stopped medication after a month due to financial constraint. The response rate at 3 months of lower dose of dasatinib 50mg daily and Imatinib were 68.75% and 69.7% respectively. At 12 months 68% and 66.6% patients achieved major molecular response [BCR-ABL≤0.1%] in dasatinib 50mg and imatinib group respectively. Dasatinib 50mg is showed somewhat similar profile in comparison to early molecular response [EMR], but patient on lower dose dasatinib achieved a good percentage of deep molecular response [MR4.0: BCR-ABL ≤ 0.01% and MR4.5: BCR-ABL ≤ 0.0032%] even at 6 months i.e., 05 (16.1%) and 02 (6.45%) respectively. Six (12%) patients switched to other TKI (Toxicity: 02 & Suboptimal Response/Failure: 04) and 10 (20%) of patients required dose escalation in view of suboptimal response/failure with low dose dasatinib 50mg daily group.

Treatment was well tolerated in lower dose dasatinib 50mg daily group. Weight gain (04), Constipation (02), Thrombocytopenia (05), Elevated Liver Enzymes (02). Diarrhoea (03), Oral mucositis (01) and Skin Hypopigmentation (01) was observed in dasatinib 50mg daily group. All patients were alive in low dose dasatinib 50mg daily group whereas 2 patients expired in imatinib group and the cause is unknown.

Conclusion:

Lower dose dasatinib is safe and effective as an upfront therapy in CML-CP. Lower dose dasatinib showed faster and deeper molecular response as compared to Imatinib. Dasatinib, taken daily at a dose of 50 mg, may offer a new, cost-effective choice for frontline therapy in CML-CP.

No relevant conflicts of interest to declare.