Treatment-free Remission (TFR) in Patients (pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated with Second-Line Nilotinib (NIL): First Results from the ENESTop Study.

7054 Background: The ENESTop (NCT01698905) study explores the discontinuation of NIL therapy in pts who achieved sustained MR4.5 (BCR-ABL1IS≤ 0.0032%) after switching from imatinib (IM) to NIL. Methods: The single-arm phase 2 study enrolled pts with CML-CP treated with tyrosine kinase inhibitor (TKI) for ≥ 3 y (including IM for > 4 wk followed by NIL for ≥ 2 y) and achieved MR4.5 on NIL. On study, pts continued NIL for 1 y (consolidation phase [CONS]). After 1 y, pts without confirmed loss of MR4.5 (consecutive BCR-ABL1IS > 0.0032%), were eligible to stop NIL (TFR). RQ-PCR was monitored every 12 wk in CONS and every 4 wk during first 48 wk of TFR. Upon confirmed loss of MR4 (consecutive BCR-ABL1IS > 0.01%) or loss of MMR (BCR-ABL1IS> 0.1%), NIL was re-initiated (ReRx). Primary endpoint was the proportion of pts with successful TFR (neither loss of MMR nor confirmed loss of MR4 by 48 wk of TFR) after a ≥ 48 wk follow up (data cutoff, 26 Nov 2015). Results: Of the 163 pts in CONS, 126 entered TFR (median duration of TKI prior to TFR, 87.7 mo; median duration of NIL, 53 mo). At data cut-off, of the 126 pts, 57.9% (95% CI: 48.8-66.7) remained in TFR at 48 wks. Median follow up in TFR was 49.8 wk. During TFR, 18 pts had confirmed loss of MR4 (1 pt did not enter ReRx due to investigator decision), 34 lost MMR and one pt came off study for atypical transcript. Of the 51 pts who re-initiated NIL, 50 (98%) regained at least MMR by data cut-off, and 48 (94.1%) and 47 (92.2%) regained MR4 and MR4.5, respectively; 1 pt switched to another TKI, 22 wk after restart (BCR-ABL1IS: 62% at restart, 3% at study exit). Median time to regain MR4 was 12 wk and 13.1 wk for MR4.5. No new safety findings were observed on treatment. In CONS vs TFR, the rates of all grade (grade 3/4) musculoskeletal pain were 14.3% (0%) vs 42.1% (1.6%), cardiovascular events were 4.8% (2.4%) vs 0% (0%), and fluid retention were 1.6% (0%) vs 10.3% (0%). Conclusions: To date this is the largest prospective TFR data set in a population of pts who achieved a sustained deep molecular response after switching from IM to NIL. The study showed that TFR attempts are safe and that TFR is likely to be achievable in the majority of pts in this setting. Clinical trial information: NCT01698905.