Second-line nilotinib may lead to maintained molecular response and treatment-free remission that can last 48 weeks or longer for patients with chronic myeloid leukemia (CML), findings from a phase 2 study suggest.

Treatment-free remission (TFR) is an emerging treatment goal for patients with CML in the chronic phase, according to François-Xavier Mahon, MD, PhD, of the University of Bordeaux (France) and his colleagues. “Potential motivators and benefits of achieving TFR may include relief of treatment side effects, reduced risk for long-term [tyrosine kinase inhibitor] toxicity, and the ability to plan a family,” they wrote. “When TFR is a treatment goal, achievement of [deep molecular response] is a key prerequisite.”

Established molecular response benchmarks include major molecular response (MMR), MR4 and MR4.5, according to the researchers.

In an open-label phase 2 study , the researchers enrolled patients with Philadelphia chromosome-positive CML who received nilotinib for 2 years or longer after having received imatinib for longer than 4 weeks. The other key criterion for enrollment was achieving MR4.5 during treatment with nilotinib, according to the study, published in Annals of Internal Medicine .

In total, 163 patients were enrolled and entered the 1-year consolidation phase. Of those patients, 126 were eligible for the TFR phase during which nilotinib treatment was stopped.

Dr. Mahon and his colleagues reported that 73 (58%) patients in the TFR phase maintained TFR at 48 weeks, 67 of whom had MR4.5. Of the seven patients who had a loss of MR4.5, four did not have a loss of MMR or confirmed loss of MR4, according to the researchers.

While the primary endpoint was TFR at 48 weeks, the researchers reported that 53% of patients maintained TFR at 96 weeks. Some patients had reinitiated nilotinib by the 96-week cutoff. Of those patients, the study showed that 93% regained MR4 and MR4.5.

The researchers noted that the safety findings were consistent with previously published data of nilotinib. “Improvements in quality of life have been cited as a motivator for stopping treatment,” they wrote. “Minimal changes in quality of life were seen with treatment cessation, possibly because the patients in this study already had a relatively high quality of life, given that they had tolerated at least 3 years of nilotinib therapy before stopping treatment.”

Novartis Pharmaceuticals funded the study. Dr. Mahon and other researchers reported financial ties to several pharmaceutical companies, including Novartis.

SOURCE: Mahon FX et al. Ann Intern Med. 2018 Feb 20. doi: 10.7326/M17-1094 .


You May Also Like