Introduction

The Dasatinib Versus Imatinib Study in Treatment- Naive Chronic Myeloid Leukemia Patients (DASISION) study was a randomized phase III trial comparing the efficacy and safety of dasatinib with imatinib in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP).

Aim

To report the 5-year analysis from the phase III DASISION trial, evaluating long-term efficacy and safety outcomes of patients with CML in CP treated with dasatinib or imatinib.

Patients Profile

Patients with newly diagnosed CML-CP

• Untreated CML-CP
• No pleural effusion or uncontrolled cardiovascular disease

Study Design

Study Endpoints

• The primary end point was confirmed complete cytogenetic response (cCCyR) rate by 12 months
• Secondary end points were overall time to cCCyR and its duration, major molecular response (MMR) rate at any time, time to MMR overall, PFS, and OS

Results

After 5 years, 61% of dasatinib-treated patients and 63% of imatinib-treated patients were still on initial therapy

Abbreviation: AE, adverse event.

*As decided by investigator. Intolerance is defined as recurrent grade $ 3 hematologic toxicity or grade > 2 nonhematologic toxicity requiring discontinuation despite dose reduction.

†Includes insufficient molecular response (n = 3), pregnancy (n = 2), loss of complete cytogenetic response (n = 1), increased BCR-ABL1 (n = 1), and relocation to the United States (n = 1).

‡Includes no molecular response/loss of molecular response (n = 4), suboptimal response (n = 3), insufficient cytogenetic response (n = 2), investigator request (n = 2), pregnancy (n = 1), recurrence of blasts in bone marrow(n = 1), no complete molecular response (n = 1), no major molecular response (n = 1), and appearance of mutation (n = 1).

Efficacy Analysis

• Transformations to both accelerated and blast phase CML on study or after discontinuation: dasatinib, 4.6%; imatinib, 7.3%
• A higher percentage of dasatinib treated patients achieved BCR-ABL1<10% (IS) at 3 months
  • 84% in dasatinib arm
  • 64% in imatinib arm
• In both arms, patients who achieved BCR-ABL1 <10% (IS) at 3 months more often reached CCyR, MMR, andMR4.5 by 5 years had higher rates of OS and PFS and had a lower transformation rate (3% v 14% to 15% in patients who did not achieve BCR-ABL1 < 10% at 3 months)

• Mutations were identified in 15 patients in dasatinib arm and 19 patients in imatinib arms

• T315I mutations were identified in eight dasatinib-treated patients and no imatinib-treated patients

Safety Analysis

• The safety profile for dasatinib remains consistent, with no new safety signals identified after 5 years

• Overall, most AEs reported with both drugs were grade 1 or 2; 15% of AEs reported with dasatinib and 11% of AEs reported with imatinib were grade 3 or 4
• Drug-related pleural effusion was more common with dasatinib (28%) than with imatinib (0.8%)
• First occurrences of pleural effusion were reported with dasatinib, with the highest incidence in year 1
• Arterial ischemic events were uncommon in both treatment arms

Conclusion

• The 5-year long-term results from DASISION demonstrated that patients taking dasatinib had faster and deeper MRs than patients taking imatinib
• The study results confirm that dasatinib treated patients have high MR rates and that the achievement of BCR-ABL1< 10% (IS) at 3 months is predictive of significantly higher PFS and OS rates
• No new safety signals observed with dasatinib through 5 years or with longer follow-up
• These results suggest that first-line dasatinib should continue to be considered a standard first-line therapy for patients with newly diagnosed CML-CP

Reference

J Clin Oncol 34:2333-2340