©ASCO/Phil McCarten
CHICAGO—Patients with chronic myeloid leukemia (CML) are more likely to achieve a deep molecular response if they switch to nilotinib rather than remain on imatinib, updated research suggests.
Patients with detectable disease who crossed over from imatinib to nilotinib after 24 months on the ENESTcmr study were able to achieve deep molecular responses (MR 4.5) by 36 months.
But none of the patients who remained on imatinib achieved undetectable BCR-ABL transcripts.
“Longer follow-up supports switching from imatinib to nilotinib to attain deep molecular responses,” said study investigator Nelson Spector, MD, of Federal University of Rio de Janeiro in Brazil.
“Achievement of deeper molecular responses with nilotinib therapy may increase patient eligibility for treatment-free remission trials.”
Dr Spector presented these results—an update of the ongoing, phase 3 ENESTcmr study—at the 2014 ASCO Annual Meeting (abstract 7025).
The study included 207 patients with Philadelphia-chromosome-positive CML in chronic phase who were treated with imatinib for at least 2 years and achieved complete cytogenetic response but had detectable BCR-ABL transcripts.
With 36 months’ follow-up, rates of MR 4.5 remained higher with nilotinib vs imatinib (47% vs 33%). The median time to achievement of MR 4.5 was 24 months with nilotinib and was not reached with imatinib after the 36-month follow-up.
“Patients experienced a rapid reduction in median BCR-ABL levels within the first 3 months after crossover from imatinib to nilotinib,” Dr Spector said. “No patient with detectable BCR-ABL at 24 months who remained on imatinib achieved this response with another year of follow-up.”
MR 4.5 rates were higher by 12 months in patients randomized to nilotinib (33%) than patients who crossed over from imatinib to nilotinib (21%).
“Three years follow-up shows the ability to achieve undetectable BCR-ABL status with nilotinib as we strive to achieve deep molecular responses with the potential to stop therapy,” said ASCO discussant Michael Mauro, MD, of the Memorial Sloan-Kettering Cancer Center in New York.
However, he questioned whether MR 4.5, “the last, deepest milestone of relevance, is enough to assess stopping.”
By 3 years of follow-up, 93 patients (92.1%) on nilotinib and 72 patients (69.9%) on imatinib had drug-related adverse events.
The most common events with nilotinib were headache, rash, and pruritus. With imatinib, the most common events were muscle spasms, nausea, and diarrhea. More cardiovascular events were reported in patients randomized to nilotinib compared with imatinib.
“Nilotinib-treated patients experienced adverse events early after switching from long-term imatinib therapy,” Dr Spector said. “These adverse events were expected and consistent with the safety profile of nilotinib observed in other studies.”
