Imatinib efficacy for CML sustained over time
medwireNews: Overall survival among patients with chronic myeloid leukemia (CML) remains high after nearly 11 years of treatment with imatinib, analysis of phase III study data shows.
In addition, “[n]o new safety signals and few drug-related serious adverse events were observed during the later years of follow-up, and molecular and cytogenetic response rates were high among the patients who could be evaluated,” Andreas Hochhaus (Universitä̈tsklinikum Jena, Germany) and fellow investigators report.
The phase III International Randomized Study of Interferon and STI571 (IRIS) randomly assigned 1106 patients with newly diagnosed CML in the chronic phase to receive either the tyrosine kinase inhibitor imatinib (n=553) or interferon alfa plus cytarabine (n=553).
However, after a median of 0.8 years, 65.6% of patients assigned to interferon alfa plus cytarabine crossed over to imatinib because of disease progression or lack or loss of response (31.5%), unacceptable side effects (26.2%), or reluctance to continue with the assigned study drug (8.0%). Just seven (1.3%) patients completed study treatment in this group.
The researchers therefore focussed their analysis on patients assigned to the imatinib group at study entry. These patients had a median treatment duration of 8.9 years, with 267 (48.3%) completing study treatment.
At 10 years, the estimated overall survival rate among patients in the imatinib group was 83.3%, while the estimated proportion who remained free from progression to the accelerated phase or blast crisis was 92.1%. And the researchers note that most events of disease progression occurred during the first 4 years of study treatment.
In addition, 91.8% of 134 evaluable patients had a complete cytogenetic response at 10 years, while 93.1% of 204 patients achieved a major molecular response and 63.2% a molecular response 4.5, defined as BCR–ABL1 values of 0.1% or less and 0.0032% or less on the International Scale, respectively.
The investigators also point out that serious adverse events related to imatinib were “uncommon”, occurring in 9.3% of patients, and no new safety signals were observed since their earlier 5-year analysis.
“With more than 10 years of follow-up in IRIS, the long-term outcomes in imatinib-treated patients that we describe here confirm and extend earlier findings,” Hochhaus and co-authors write in The New England Journal of Medicine.
However, they accept that their findings are reported with several caveats. These include a high number of patients with unknown survival status or unevaluable molecular and cytogenetic assessments, and limited collection of long-term safety information.
“Nonetheless, these results highlight the safety and efficacy of imatinib therapy, with a clear improvement over the outcomes that were expected in patients who received a diagnosis of CML before the introduction of tyrosine kinase inhibitor therapy, when interferon alfa and hematopoietic stem-cell transplantation were the standard therapies,” the researchers conclude.
In an accompanying editorial Dan Longo, from the Brigham and Women’s Hospital in Boston, Massachusetts, USA, says the data show that “imatinib is highly successful at controlling [CML] in the long term.”
He adds that the “imatinib story” shows that understanding CML pathogenesis “led to a less toxic and more effective treatment approach” and “[t|he development of imatinib fundamentally altered the field of oncology.”
By Laura Cowen
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