Switch from imatinib to nilotinib improved outcomes in chronic phase CML

Patients with chronic phase chronic myeloid leukemia who had persistent minimal residual disease after long-term treatment with imatinib achieved deeper molecular responses and undetectable disease when they switched to treatment with nilotinib, according to study results.

The reduced disease burden associated with the switch to nilotinib may enable patients to enroll on treatment-free remission trials, researchers wrote.

Timothy P. Hughes, MD, FRACP, FRCPA, head of the division of hematology at South Australia Pathology and clinical professor of medicine at University of Adelaide in Australia, and colleagues evaluated data from 207 patients with CML. All patients were in complete cytogenetic response yet had detectable BCR-ABL1 after 2 or more years of treatment with imatinib (Gleevec, Novartis).

Hughes and colleagues randomly assigned 104 patients to 400 mg twice-daily nilotinib (Tasigna, Novartis), and 103 patients to continued imatinib.

After 1 year, more patients who switched to nilotinib demonstrated confirmed undetectable BCR-ABL1 than those who continued therapy with imatinib; however, this difference did not reach statistical significance (12.5% vs. 5.8%; P=.1083). After 2 years, significantly more patients assigned nilotinib vs. imatinib had undetectable BCR-ABL1 (22.1% vs. 8.7%; OR=2.565; 95% CI, 1.107-5.947).

Among patients who had not achieved molecular response 4.5 (MR^4.5) — or BCR-ABL1 ≤0.0032% — at baseline, a higher percentage of those assigned nilotinib achieved MR^4.5 by 2 years (42.9% vs. 20.8%). Among patients who had not achieved major molecular response at baseline, a higher percentage of those assigned nilotinib achieved MR^4.5 by 2 years (29.2% vs. 3.6%).

More patients who continued imatinib had a confirmed loss of major molecular response (4 vs. 2) and a loss of complete cytogenetic response (3 vs. 0).

Patients in the nilotinib arm experienced a higher rate of grade 3 or grade 4 adverse events (48.5% vs. 22.3%) and more frequently discontinued therapy due to an adverse event of any grade (19.8% vs. 5.8%).

“In patients with molecular responses less than MR^4.5, the clinical benefits of switching to nilotinib to achieve deeper molecular responses should be carefully weighed against the potential for adverse events, including cardiovascular adverse events, on an individual basis,” Hughes and colleagues wrote. “For physicians involved in the treatment of CML, adverse events that occur after TKI switch must be viewed in light of the fact that patients who achieve deeper responses such as MR^4.5 are likely to have better long-term outcomes.”

Disclosure: The researchers report consultant roles or employment with; honoraria, research funding or other remuneration from; and stock ownership in Ariad, Bristol-Myers Squibb, CSL Behring, Novartis, Pfizer and Teva.