One-year and long-term molecular response to nilotinib and dasatinib for newly diagnosed chronic myeloid leukemia: a matching-adjusted indirect comparison

Abstract

Background:

Nilotinib and dasatinib have shown superior rates of molecular response (MR) compared to imatinib for the treatment of newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP). This study indirectly compares MR in patients taking nilotinib 300 mg bid with that in those taking dasatinib 100 mg qd by 12 months and through 48 months.

Methods:

Patients in ENESTnd were re-weighted to match published baseline characteristics reported for DASISION using a propensity score model. After matching, differences in rates of major MR (MMR, measured as a 3 log reduction on the International Scale [IS]), MR^4.0 (4 log reduction on IS), and MR^4.5 (4.5 log reduction on IS) relative to imatinib were indirectly compared between nilotinib and dasatinib. Hazard ratios (HRs) were used to indirectly compare MR outcomes between nilotinib and dasatinib through 48 months of follow-up, while rate differences were used to compare progression to AP/BC between nilotinib and dasatinib by 48 months.

Results:

After matching, rates of MR by 12 months were higher with nilotinib vs dasatinib by 11.7% for MMR (p = 0.045), 8.2% for MR^4.0 (p = 0.029), and 8.5% for MR^4.5 (p < 0.001). Higher rates of MMR (HR = 1.44, p = 0.018) and MR^4.0 (HR = 1.58, p = 0.013) achievement were maintained with nilotinib compared to dasatinib through 48 months of follow-up. No statistically significant differences were observed for MR^4.5 through 48 months or progression to AP/BC by 48 months.

Limitations:

Limitations include comparisons based solely on indirect evidence and HRs for MR^4.0 and MR^4.5 from the DASISION trial being extracted from cumulative incidence curves.

Conclusions:

This indirect comparison suggests that nilotinib is associated with higher rates of achieving MMR, MR^4.0, and MR^4.5 by 12 months compared to dasatinib for the treatment of newly diagnosed CML-CP. In addition, higher rates of MR achievement with nilotinib were also maintained through 48 months of follow-up.

Keywords: :

• Chronic myeloid leukemia
• Dasatinib
• Indirect comparison
• Long-term molecular response
• Nilotinib

Transparency

Declaration of funding

Research was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.

Author contributions: All authors participated in the design of the study. E.Q.W., J.E.S., K.A.B., W.M.R., P.G., and D.T. conducted analyses. E.Q.W., J.E.S., K.A.B., W.M.R., P.G, D.T., L.C., and D.J.D. have interpreted results. All authors contributed to manuscript development.

Declaration of financial/other relationships

E.Q.W., J.E.S., K.A.B., W.M.R., P.G., and D.T. have disclosed that they are employees of Analysis Group Inc., a company that received funding from Novartis Pharmaceuticals Corporation to conduct this study. L.C. has disclosed that she is an employee of Novartis Pharmaceuticals Corporation. D.J.D. has disclosed that he has been a consultant for Novartis, BMS, Pfizer, and Ariad.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose.