Long-term treatment-free remission for patients with chronic phase chronic myeloid leukemia after second line nilotinib treatment 

This study aimed to investigate long-term treatment-free remission (TFR) for patients with chronic-phase (CP) chronic myeloid leukemia (CML) who were treated with nilotinib (Tasigna) as a second-line treatment.  

This study concluded that TFR is safe and durable in these patients.  

The diagnosis of CML is made by finding in the blood of patients a genetic change (mutation) called BCR-ABL. The outcomes of patients with CP-CML have been improved in recent years by the approval of tyrosine kinase inhibitors (TKIs) such as imatinib (Gleevec).  

TKI treatment usually leads to a decrease in the BCR-ABL gene. This is called a molecular response (MR). If a very low level of BCR-ABL gene is found in the blood after TKI treatment, it is called a major molecular response (MMR). After patients maintain MR for a certain amount of time under TKI treatment, the treatment can be stopped. If patients maintain MR without treatment, this is called TFR. 

Some patients do not achieve TFR with first-line imatinib treatment. These patients are usually switched to a second-line TKI such as nilotinib. The TFR outcomes of patients with CP-CML on nilotinib after switching from imatinib treatment are still not clear. 

This study involved 126 patients who attempted TFR after achieving MR with nilotinib as a second line treatment. All patients had previously received at least 3 years of TKI therapy, with at least 2 years with nilotinib. After achieving MR, patients had another year of nilotinib consolidation therapy. This is meant to kill any cancer cells left behind. TFR was attempted after patients maintained MR during the 1 year of consolidation therapy. 

At 48 weeks, 73 (57.9%) patients were in TFR. At 5 years, 52 patients (42.9%) were still in TFR. Out of the 74 patients who lost MR during 5 years, 59 patients reinitiated nilotinib. Of these 58 (98.3%) regained MMR.  

Longer time on nilotinib before TFR and longer time in MR on nilotinib before TFR were associated with longer higher TFR rates.

Overall side effects decreased over the 5 years of TFR. The most common side effects were joint and muscle pain and high blood pressure. In patients restarting nilotinib, there was an increase in heart-related side effects.  

This study concluded that TFR is safe and durable for patients with CP-CML who have received nilotinib as a second-line treatment. 

This study did not compare outcomes between patients who stopped treatment and those who continued on nilotinib. This study was funded by Novartis, the manufacturer of nilotinib.