Patients with chronic myeloid leukemia in chronic phase (CML-CP) who do not respond to first-line imatinib may benefit from early monitoring in order to switch to treatment with dasatinib, according to the results of the phase 2b DASCERN study.
About 1 in 3 patients treated with first-line imatinib will not achieve early molecular response, lowering their chances of achieving deep molecular response. The DASCERN trial was designed to see if an early switch to dasatinib in those patients with suboptimal response to imatinib would improve response rates.
The study randomly assigned treatment to suboptimal responders 2:1 to 100 mg dasatinib (174 patients) or continued treatment with 400 mg or more imatinib (86 patients).
The primary endpoint of major molecular response at 12 months was achieved in about one-third (29%) of patients assigned dasatinib compared with 13% of patients who continued on imatinib (P =.005).
After more than 2 years of follow-up, more than one-half of patients had crossed over to dasatinib. The median time to crossover was 9 months. Considering this, the 2-year cumulative major molecular response rate was 64% with dasatinib compared with 41% with imatinib.
“When accounting for competing risk, the cumulative incidence of major molecular response was higher in patients in the dasatinib arm than the imatinib arm; however, this finding was not statistically significant as these results were influenced by 30% of patients from the imatinib arm achieving MMR after crossing over to dasatinib,” the researchers explained.
No differences in overall survival or progression-free survival were noted between the two treatment arms, and adverse events were consistent with the known effects of both drugs.
“These data support the importance of early monitoring for patients who do not receive a second-generation TKI as their first-line treatment, and suggest that preemptive switching to dasatinib in such instances may provide clinical benefit,” the researchers concluded.
Cortes JE, Jiang Q, Wang J, et al. Dasatinib vs. imatinib in patients with chronic myeloid leukemia in chronic phase (CML-CP) who have not achieved an optimal response to 3 months of imatinib therapy: the DASCERN randomized study [published online April 7, 2020]. Leukemia. doi: 10.1038/s41375-020-0805-1.