Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial

Abstract

Purpose: We report the 5-year analysis from the phase III Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients (DASISION) trial, evaluating long-term efficacy and safety outcomes of patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with dasatinib or imatinib.

Patients and methods: Patients with newly diagnosed CML-CP were randomly assigned to receive dasatinib 100 mg once daily (n = 259) or imatinib 400 mg once daily (n = 260).

Results: At the time of study closure, 61% and 63% of dasatinib- and imatinib-treated patients remained on initial therapy, respectively. Cumulative rates of major molecular response and molecular responses with a 4.0- or 4.5-log reduction in BCR-ABL1 transcripts from baseline by 5 years remained statistically significantly higher for dasatinib compared with imatinib. Rates for progression-free and overall survival at 5 years remained high and similar across treatment arms. In patients who achieved BCR-ABL1 ≤ 10% at 3 months (dasatinib, 84%; imatinib, 64%), improvements in progression-free and overall survival and lower rates of transformation to accelerated/blast phase were reported compared with patients with BCR-ABL1 greater than 10% at 3 months. Transformation to accelerated/blast phase occurred in 5% and 7% of patients in the dasatinib and imatinib arms, respectively. Fifteen dasatinib-treated and 19 imatinib-treated patients had BCR-ABL1 mutations identified at discontinuation. There were no new or unexpected adverse events identified in either treatment arm, and pleural effusion was the only drug-related, nonhematologic adverse event reported more frequently with dasatinib (28% v 0.8% with imatinib). 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: These final results from the DASISION trial continue to support dasatinib 100 mg once daily as a safe and effective first-line therapy for the long-term treatment of CML-CP.

Fig 1.

CONSORT diagram for the DASISION trial after a minimum follow-up of 5 years. CML-CP, chronic myeloid leukemia in chronic phase; Ph+, Philadelphia chromosome positive. (*) Reasons for discontinuation are listed in Table 1.

Fig 2.

Cumulative response rates over time. The percentages of patients with (A) major molecular response (MMR) and (B) molecular response with a 4.5-log reduction in BCR-ABL1 transcripts from baseline (MR^4.5; BCR-ABL1 transcript level ≤ 0.0032% [International Scale]) by 1, 2, 3, 4, and 5 years are shown.

Fig 3.

Estimated 5-year (A, B) overall survival (OS) and (C, D) progression-free survival (PFS) by molecular response at 3 months for both treatment arms. OS and PFS were calculated using patients on study treatment and in follow-up after discontinuation of randomly assigned treatment.

Fig 4.

Drug-related, nonhematologic adverse events (AEs) reported in ≥ 10% of patients. Odds ratios (dasatinib v imatinib) with 95% CIs are shown for AEs that occurred in ≥ 10% of patients. Blue favors dasatinib, and gold favors imatinib.

Fig A1.

(A) Major molecular response (MMR) and (B) molecular response with a 4.5-log reduction in BCR-ABL1 transcripts from baseline (MR^4.5; BCR-ABL1 transcript level ≤ 0.0032% [International Scale]) at any time by Euro (Hasford) risk score.

Fig A2.

Kaplan-Meier curves for (A) overall survival and (B) progression-free survival in both treatment arms. A sensitivity analysis of progression-free survival was performed to include patients who discontinued treatment and experienced progression or died on treatment or during follow-up.

Fig A3.

Expected survival by age at diagnosis for both treatment arms and a general population of patients without chronic myeloid leukemia. (*) Expected life span estimates were adapted from Ludwig et al.