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Nearly half of PH+ CML-CP patients remain in treatment-free remission 96 weeks after discontinuing treatment with nilotinib

Updated results from ENESTfreedom, which evaluates the ability to discontinue nilotinib in adult patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the chronic phase (CP) who achieved a sustained deep molecular response (DMR) following at least 3 years of first-line treatment with nilotinib were presented at EHA 2017. Almost half of the patients (48.9%) were able to discontinue therapy and remain in major molecular response (MMR) at 96 weeks.

Patient enrolled in the ENESTfreedom study had Ph+ CML-CP, ≥ 2 years of frontline nilotinib, and MR 4.5 prior to enrollment. After enrollment, patients continued nilotinib for 1 year (consolidation phase). MR was assessed every 12 weeks during the 1 year consolidation phase; patients with no assessment worse than MR4, ≤ 2 assessments between MR4 and MR4.5, and MR4.5 in the last assessment were eligible to enter treatment-free remission (TFR). Loss of MMR during TFR triggered re-initiation of nilotinib. The current analysis was conducted when all patients who entered TFR, had completed 96 weeks of TFR, reinitiated therapy, or discontinued from the study.

Of the 190 patients who entered TFR, 93 (48.9% [95% CI, 41.6% - 56.3%]) remained in MMR and off treatment at week 96, including 88 (46.3%) who were in MR4.5. Three patient who were in TFR at 48 weeks lost MMR by 96 weeks, and 2 additional patients discontinued from the study between 48 and 96 weeks without losing MMR. Overall, of the 88 patients who reinitiated nilotinib due to loss of MMR, 87 (98.9%) regained MMR and the remaining patient left the study 7.1 week after nilotinib re-initiation without regaining MMR.

To investigate potential predictors for remaining in TFR, patients were grouped according to Sokal risk score at diagnosis or depth of response prior to attempting TFR (based on response assessments in the consolidation phase). Among patients with low, intermediate, or high Sokal risk at diagnosis, 39/62 (62.9% [95% CI, 49.7% - 74.8%]), 25/50 (50.0% [95% CI, 35.5% - 64.5%]), and 9/28 (32.1% [95% CI, 15.9% - 52.4%]), respectively, remained in TFR at week 48. Among patients with MR4.5 in all assessments during the consolidation phase, 90/170 (52.9% [95% CI, 45.2% - 60.6%]) remained in TFR at week 48 versus 8/20 (40.0% [95% CI, 19.1% - 63.9%]) who had ≥ 1 assessment between MR4 and MR4.5 during the consolidation phase.

Moreover, no new safety findings were reported. Among patients remaining in TFR for > 48 weeks (n=100), adverse events were less frequent during the second versus the first 48 weeks of TFR; 2 (2.0%) and 1 (1.0%) of these patients had cardiovascular adverse events during the first and second 48 weeks of TFR, respectively and 34 (34.0%) and 9 (9.0%) had adverse events in the predefined musculoskeletal pain grouping.

In conclusion, the majority of patients in TFR at 48 weeks remained in TFR at 96 weeks, and they reported fewer adverse events during the second 48 weeks of TFR than in the first 48 weeks. These data affirm the durability and safety of TFR following nilotinib. In addition, no strong predictors for remaining in TFR were identified. Patients with low Sokal risk and patients with continuous MR4.5 in the consolidation phase tended to have higher TFR rates than other patients, although these results must be interpreted with caution due to the small number of patients in some subsets and the wide 95% CIs. Overall, these results support TFR as a valuable option for patients with CML-CP in sustained DMR on frontline nilotinib (for > 3 years).


D. Ross, T. Masszi , MT Gómez Casares, et al. Durable treatment-free remission (TFR) following frontline nilotinib (NIL) in patients (PTS) with chronic myeloid leukemia in de chronic phase (CML-CP): ENESTfreedom 96-wk update. EHA 2017, poster presentation, abstract P601.


Speaker David Ross


David Ross, MD, PhD, SA Pathology, Flinders Medical Center, Adelaide, Australia


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