With the emergence of second-generation tyrosine kinase inhibitors (TKIs), more choices than ever exist for treating patients with chronic-phase chronic myeloid leukemia (CML-CP). However, little is known about how the long-term outcomes of these drugs compared to standard-dose imatinib.
In a new retrospective cohort analysis published in The Lancet Haematology, investigators from MD Anderson Cancer Center assessed treatment response and long-term survival in 482 CML-CP patients treated with any of four different TKI modalities:
- imatinib 400 mg daily (standard-dose imatinib, n=68)
- imatinib 800 mg daily (n=200)
- dasatinib 50 mg twice daily or 100 mg once daily (n=106)
- nilotinib 400 mg twice daily (n=108)
The team of investigators, led by Preetesh Jain, MD, compared the long-term molecular and cytogenetic response and survival (including event-free survival, failure-free survival, transformation-free survival, and overall survival). Ultimately, they found that treatment with imatinib 800 mg or the second-generation TKIs produced superior and deeper responses than standard-dose imatinib.
While researchers observed no significant differences among the four groups in five-year failure-free survival, transformation-free survival, or overall survival rates, they did note several distinctions for those taking standard-dose imatinib.
For instance, 87 percent of patients taking imatinib 400 mg achieved a complete cytogenetic response, compared to 90 percent of those taking imatinib 800 mg, 96 percent of those taking dasatinib, and 93 percent of those taking nilotinib. The percentage of patients achieving a major molecular response (defined as a three-log reduction in transcripts of the molecular lesion that defines CML) was also less for those taking standard-dose imatinib: 76 percent compared with 86 percent of the imatinib 800 mg group, 90 percent of the dasatinib group, and 91 percent of the nilotinib group. These findings were consistent over time, the investigators noted.
Five-year event-free survival also differed significantly between the imatinib 400 mg group and other TKI groups (compared to imatinib 800 mg, p=0.029; dasatinib, p=0.003; nilotinib, p=0.031).
In multivariate analysis, treatment with higher-dose imatinib (HR=0.51; p=0.016), dasatinib (HR=0.28; p=0.004), and nilotinib (HR=0.42; p=0.024) was associated with better event-free survival compared with standard-dose imatinib. However, rates of failure-free, transformation-free, and overall survival were similar irrespective of the TKI used.
Investigators also found that it took longer for patients taking imatinib 400 mg to achieve a complete cytogenetic response and major molecular response compared to the other groups.
“Our analysis shows that long-term outcomes of higher-dose imatinib is similar to second-generation TKIs,” Dr. Jain told ASH Clinical News. “Therefore, in situations where newer TKIs are beyond the reach of patients, imatinib 800 mg can be used without compromising the outcomes – provided the patients are able to tolerate it.”
The most significant finding of the study, Dr. Jain noted, is that all four treatment options achieved excellent results with no significant difference in overall survival among the groups, giving physicians more flexibility as they try to match the best medication with individual patients.
“Treatment selection for an individual patient is a complex decision that is affected by multiple factors, including availability, cost, familiarity with the drug, schedule of administration, risk factors for certain expected adverse events with a given agent, and others,” Dr. Jain said.
Jain P, Kantarjian H, Alattar ML, et al. Long-term molecular and cytogenetic response and survival outcomes with imatinib 400 mg, imatinib 800 mg, dasatinib, and nilotinib in patients with chronic-phase chronic myeloid leukaemia: retrospective analysis of patient data from five clinical trials. Lancet Haematol. 2015;2:e118-e128.