Nilotinib May Lead to Increased Rates of Treatment-Free Remission in Chronic-Phase CML

CHICAGO—Second-line nilotinib may produce durable treatment-free response (TFR) among patients with chronic-phase chronic myeloid leukemia (CP-CMP), and may even reproduce deep molecular response (MR^4.5) among patients who restart nilotinib therapy, according to an oral presentation at the American Society of Clinical Oncology 2018 Annual Meeting on Saturday, June 2.¹

Data from a previous study supports TFR as a new treatment goal for patients with CP-CML who achieve sustainable deep molecular response after second-line nilotinib; 57.9% sustained response after 48 weeks and 53.2% sustained response after 96 weeks. Longer-term durability, however, has not yet been investigated.

In the phase 2 ENESTop study (ClinicalTrials.gov Identifier: NCT01698905), researchers enrolled 163 patients with CP-CML who were previously treated with imatinib for longer than 4 weeks and then switched to nilotinib; treatment was continued for at least 2 years. Patients with MR^4.5, who did not have confirmed loss of MR^4.5 after 1-year consolidation therapy, were able to enter the TFR phase. Patients who lost major molecular response (MMR) or MR⁴ were able to restart nilotinib.

At the time of data cutoff 61 of 126 patients who entered TFR remained in TFR and 58 restarted nilotinib; 34 patients had a loss of MMR, 24 had confirmed loss of MR⁴, and 7 patients discontinued the study.

At week 144, the TFR rate was 48.4% (95% CI, 39.4-57.5). Of 67 patients who were in TFR by week 96, 6 patients were no longer in TFR by week 144 due to death, study discontinuation, or loss of MR⁴.

Of the 34 patients who had lost MMR and restarted nilotinib, 97.1% (33) regained MMR and 91.2% (31) regained MR^4.5; 23 of 24 patients who reinitiated nilotinib due to the loss of MR⁴ regained MR^4.5. Of the 54 patients who regained MR^4.5, 77.8% (42) had stable MR^4.5 after 48 weeks.

The 144-week treatment-free survival rate was 52.0% (95% CI, 42.9-60.4) and no disease progression or deaths due to CML were observed.

The 68 patients who maintained TFR for longer than 96 weeks experienced any-grade musculoskeletal pain-related adverse events (AEs), 10.3% experienced pain in the consolidation phase, 51.5% experienced pain in the first, 19.1% experienced pain in the second, and 11.8% experienced pain in the third 48-week of TFR. Frequently reported AEs included nasopharyngitis, myalgia, arthralgia, and weight gain.

The authors concluded that “these results demonstrate the long-term durability of TFR following [second-line] nilotinib and show that most patients restarting nilotinib regained stable MR^4.5. Patients should be routinely monitored for late loss of response. Together with previous results showing higher MR^4.5 rates with a switch to second-line nilotinib versus remaining on imatinib, these findings suggest that switching to nilotinib may enable more patients to reach eligibility for attempting and achieving TFR. ”

Read more of Cancer Therapy Advisor‘s coverage of the American Society of Clinical Oncology (ASCO) 2018 meeting by visiting the conference page.

Reference

1. Mahon FX, Boquimpani C, Takahashi M, et al. Long-term treatment-free remission (TFR) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) after stopping second-line (2L) nilotinib: ENESTop 144-wk results. Oral presentation at: 2018 ASCO Annual Meeting; June 1-5, 2018; Chicago, IL.