Switching from imatinib to nilotinib plus pegylated interferon-α2b in chronic phase CML failing to achieve deep molecular response: clinical and immunological effects

In order to improve molecular response for a discontinuation attempt in chronic myeloid leukemia (CML) patients in chronic phase, who had not achieved at least a molecular response BCR-ABL1(IS) (MR4.0) after at least 2 years of imatinib therapy, we prospectively evaluated whether they could attain MR4.0 after a switch to a combination of nilotinib and 9 months of pegylated interferon-alpha 2b (PegIFN). The primary endpoint of confirmed MR4.0 at month 12 (a BCR-ABL1(IS)level <= 0.01% both at 12 and 15 months) was reached by 44% (7/16 patients, 95% confidence interval (CI): 23- 67%) of patients, with 81% (13/16 patients, 95% CI: 57-93%) of patients achieving an unconfirmed MR4.0. The scheduled combination was completed by 56% of the patients, with premature discontinuations, mainly due to mood disturbances after the introduction of PegIFN, questioning the feasibility of the combination of nilotinib and PegIFN for this patient population and treatment goal. A comprehensive clinical substudy program was implemented to characterize the impact of the treatment changes on the immunological profile.