BACKGROUND: The ENESTop study (NCT01698905) is assessing treatment-free remission (TFR) in patients (pts) with chronic myeloid leukemia (CML) in chronic phase who achieved sustained MR4.5 (4.5-log decrease from standardized baseline in BCR-ABL1 transcript level) on second-line nilotinib (2L NIL). In the primary analysis, 57.9% of pts maintained TFR at 48 wk. Overall adverse event rates were 73.8% during TFR vs 77.0% on treatment before TFR; musculoskeletal pain rates were higher during TFR (42.1% vs 14.3%).
OBJECTIVE: To assess effects of TFR on quality of life (QOL), pt-reported outcomes (PROs) were evaluated before and during TFR and after treatment reinitiation.
METHODS: Eligible pts had ≥3 y of prior tyrosine kinase inhibitor (TKI) therapy (>4 wk imatinib [IM], then ≥2 y NIL) and achieved sustained MR4.5 after switching from IM to NIL. Enrolled pts entered a 1-y consolidation phase; those without confirmed loss of MR4.5 stopped NIL and entered the TFR phase. Pts with loss of response (ie, loss of major molecular response [MMR; 3-log decrease] or confirmed loss of MR4 [4-log decrease]) during the TFR phase reinitiated NIL. PROs (exploratory endpoints) were assessed via the MD Anderson Symptom Inventory for CML (MDASI-CML), EQ-5D-5L, and EQ VAS questionnaires.
RESULTS: 126 of 163 enrolled pts met criteria for stopping NIL in the TFR phase; 53 had loss of MMR or confirmed loss of MR4 and 51 reinitiated NIL. At wk 48 of consolidation and wk 12 and 48 of the TFR phase, respectively, mean PRO scores among evaluable pts were 1.7, 1.5, and 1.2 (MDASI-CML severity); 1.7, 1.6, and 1.4 (MDASI-CML interference), and 82.2, 78.8, and 82.3 (EQ VAS). Minimal changes in these scores were seen with NIL cessation. For pts who reinitiated NIL, mean MDASI-CML severity and interference scores and EQ VAS scores at 24 wk after retreatment (1.6, 1.5, and 78.8) were similar to those at wk 48 of consolidation. For EQ-5D-5L, generally similar proportions of pts reported problems with mobility, self-care, usual activities, anxiety/depression, or pain/discomfort across time points. However, more pts reported problems with pain/discomfort during TFR vs consolidation, consistent with the increase in musculoskeletal pain events.
CONCLUSIONS: Changes in QOL after stopping 2L NIL were minimal. This may be because these pts had tolerated ≥4 y of prior TKI therapy (including ≥3 y of NIL) with good responses and thus had relatively high QOL before stopping NIL. QOL remained high despite the increased rates of musculoskeletal pain during TFR. Longer-term evaluations of QOL are ongoing with further follow-up.
