PB1946 OUTCOMES FOLLOWING TREATMENT DISCONTINUATION IN CML: REAL‐WORLD EXPERIENCE FROM 3 REGIONAL UK CENTRES
Authors: M. Kwok, A. Shenouda, N. Duncan, Y. Hasan, J. Ewing, M. Raghavan, F. Wandroo
Journal: HemaSphere (2019)

Background: Emerging evidence from clinical trials has demonstrated the feasibility of TKI discontinuation in CML. However, real‐world data of treatment discontinuation has been limited, particularly where this is due to clinical considerations such as drug toxicities. Aims: To address the real‐world outcomes of treatment discontinuation and factors influencing this. Methods: We retrospectively analysed all patients from 3 hospitals in Birmingham, UK who have discontinued CML treatment since 2010. Results: Altogether 28 patients (11 males, 17 females) discontinued TKI. Prior to discontinuation, these patients received TKI for chronic‐phase CML for a median of 8.9 years (range 4.3‐15.2 years). At the time of discontinuation, 22 were receiving frontline TKI therapy while 6 patients had 1 or 2 prior treatments including interferon‐alpha, allogeneic SCT and other TKIs. Twenty‐two patients (78.6%) discontinued imatinib, and 3 patients each (10.7%) discontinued nilotinib and dasatinib respectively. The median age at the time of discontinuation was 61 (range 18‐83). The most common reasons for TKI discontinuation were patient preference (n = 10), enrolment in a TKI discontinuation trial (DESTINY; n = 9) and TKI drug toxicity (n = 8). Seventeen patients (60.7%) achieved MR4.5, 6 patients (21.4%) achieved MR4 and 5 patients (17.9%) had remission status below MR4 at the time of TKI discontinuation. Sixteen patients (57.1%) had been in deep molecular remission (MR4 or MR4.5) for at least 5 years prior to TKI discontinuation, including 11 patients (39.3%) who had been in MR4.5 for ≥5 years. Only one patient experienced withdrawal syndrome following discontinuation. With a median follow‐up of 2.5 years (range 0.2‐5.4 years), the median treatment‐free remission (TFR) was not reached. Ten patients (35.7%) experienced molecular relapse following TKI discontinuation, and in the majority (9 of 10) of these patients relapse occurred within 6 months of TKI discontinuation. All 10 patients were restarted on TKI, with 6 of 10 patients returning to a major molecular remission. With the exception of two patients who died of a second malignancy unrelated to CML, all patients remained alive. Remission status at the time of TKI discontinuation significantly predicted for the duration of TFR (p = 0.018). The relapse rate in the initial 6 months following TKI discontinuation was 18.5% (3 of 16 patients), 33.3% (2 of 6 patients) and 80% (4 of 5 patients) for patients in MR4.5, MR4 and &lt;MR4 respectively at the time of discontinuation. There was also a trend for the TFR to be positively associated with the total duration of TKI therapy (p = 0.057) and the duration at MR4.5 (p = 0.066) prior to TKI discontinuation. There was no significant association between TFR and the type or line of TKI at discontinuation, the patient's age or their reason for discontinuation. Of note, long‐term TFR was also observed following non‐TKI treatments, including in a single patient who remained in MR4 following discontinuation 3.8 years ago of interferon‐alpha which he received for 15 years. Prior to discontinuation, the patient had been in MR4 for 9.6 years. Summary/Conclusion: Overall, our results are largely consistent with published data on TKI discontinuation in CML, demonstrating feasibility of discontinuation in clinical practice. Importantly, outcomes following discontinuation significantly correlated with the depth and duration of remission at the time of TKI discontinuation. Given the paucity of real‐word data on treatment discontinuation in CML, our study may provide additional confidence to clinicians on treatment discontinuation. image