Patients with chronic myeloid leukemia (CML) who are in complete molecular remission (CMR) can safely discontinue their treatment with imatinib, according to data from the Stop Imatinib (STIM) and Australasian Leukaemia & Lymphoma Group CML8 clinical trials. As a result, researchers are now asking whether second-generation tyrosine kinase inhibitors (TKIs) can accomplish this at an even higher rate.
Delphine Rea, MD, PhD, of the Hôpital Saint Louis, Paris, presented the initial data from the French CML Study Group that looked at sustained, treatment-free CMR after extended treatment with the second-generation TKIs dasatinib or nilotinib, which showed high rates of CMR for up to 24 months after treatment discontinuation.
The results demonstrated that these newer TKIs have superior potency against cancer-causing BCR-ABL transcripts compared with imatinib, as well as being effective as salvage therapy for patients with CML resistant to or intolerant of imatinib.
STIM Study
To perform her study, Dr Rea enrolled adult patients with chronic-phase or accelerated-phase CML who had been treated with dasatinib or nilotinib for at least 36 months, and had achieved and sustained a CMR for at least 24 months (N = 33). Two patients in the cohort had received treatment with frontline nilotinib; the remaining 31 individuals started with imatinib, but were switched to second-generation TKIs as salvage therapy. All active treatment was halted on study entry (N = 33).
The primary end point for the study was stable major molecular response (MMR) at 6 months. Patients are monitored by polymerase chain reaction once a month for the first year, then every 2 to 3 months thereafter. TKIs were reintroduced if MMR is lost.
After second-generation TKI cessation, 8 patients lost MMR at 2-month median intervals; all 8 regained MMR within 12 months of resuming TKI therapy.
The other 25 patients remained off therapy for a median of 6 months (range, 0-25 months); 15 of the 25 patients have sustained MMR to a median of 13 months. From these initial findings, Dr Rea concluded that second-generation TKIs could be discontinued without jeopardizing short-term outcomes, and that even if patients lost an MMR, they remained sensitive (nonresistant) to such treatment when reintroduced.
What Would a “Cure” Mean to Patients?
“Even defining cure is a real challenge,” said Dr Rea. “Is cure a total eradication of leukemic cells, or is cure being able to stop therapies without disease relapse? These are 2 different points.” This uncertainty has become an issue among patients. “One of the very first questions patients ask is ‘How long is the treatment going to last?’ ‘When am I going to be cured?’ So, from the patient’s perspective, being cured means being able to stop the therapy without disease recurrence,” Dr Rea said.