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TFR monitoring frequency, QoL impact reported at ASH 2016


58th American Society of Hematology Annual Meeting & Exposition;
San Diego, California, USA: 3–6 December 2016

: Posters from the 2016 American Society of Hematology Annual Meeting & Exposition suggest that patient monitoring after discontinuation of tyrosine kinase inhibitor (TKI) therapy may be feasible on a 2-monthly basis, but that patient-reported quality of life (QoL) may not improve after treatment is stopped.

Naranie Shanmuganathan, from Royal Adelaide Hospital in South Australia, and team proposed polymerase chain reaction (PCR) monitoring of patients every 2 months from TKI therapy discontinuation, stretching to a 3-month frequency after 6 months. Patients would be monitored on a monthly basis if their BCR–ABL1 level rose or fluctuated below 0.1%, and restart treatment on a rise to 0.1% or higher.

The team applied this strategy to data from 85 patients who had discontinued imatinib (75%), nilotinib (20%) or dasatinib (5%), 49 of whom restarted TKI therapy between 2.8 and 117.2 months. Most (73%) lost their major molecular response (MMR; BCR–ABL1 ≤0.1%) before restarting therapy, after a median of 3 months.

Landmark analysis showed that all patients who lost MR4.5 (BCR–ABL1 ≤0.0032%) within 2 months would restart TKI therapy, and that a further 40% of patients would later also return to TKI therapy, 19% within 6 months.

Applying this schema resulted in a 34% reduction in the need for PCR testing in the patients who returned to TKI therapy compared with conventional monthly monitoring, and would do so “while minimizing hematological relapse,” they concluded.

Findings from the ENESTfreedom and ENESTop trials of nilotinib discontinuation were also presented in posters at the meeting, both finding that treatment-free remission (TFR) did not lead to improvements in patient-reported QoL.

Andreas Hochhaus, from Universitätsklinikum Jena in Germany, and ENESTfreedom co-authors assessed the impact of TFR in 190 patients given first-line nilotinib using the MD Anderson Symptom Inventory for CML (MDASI–CML), the EuroQol EQ-5D-5L and the EQ visual analog scale assessment.

In all, 86 patients restarted treatment, the majority of whom regained MMR (98.8%) and MR4.5 (88.4%). Patients had fewer adverse events in the first 48 weeks of TFR than in the consolidation treatment phase (65.8 vs 83.2%) but musculoskeletal pain events were more common (24.7 vs 16.3%) in the TFR phrase.

Moreover, QoL results for the three measures were comparable in the treatment consolidation phase, during TFR, and after treatment restarted. This was true despite patients being slightly more likely to cite pain or discomfort on the EQ-5D-5L during TFR than consolidation, “possibly reflecting a TKI withdrawal syndrome,” the team suggests.

“The ENESTfreedom patient population likely had a relatively high QOL prior to treatment discontinuation (as all patients had already demonstrated a tolerance of nilotinib for ≥3 years prior to entering the TFR phase),” the researchers write.

Nevertheless, they note that earlier suggestions of patient concerns about TFR did not translate to an increased risk of anxiety or depression.

A similar pattern of findings was also reported after nilotinib discontinuation in participants of the ENESTop trial for patients who achieved a deep MR on nilotinib after switching from imatinib, said François-Xavier Mahon, from Institu Bergonie in Bordeaux, France, and co-authors.

Of the 126 patients who achieved MR4.5, TFR began after a median of 53.0 months of treatment with nilotinib; 51 patients restarted nilotinib following loss of MMR or MR4.

Adverse events were reported by 77.0% and 73.8% of patients in the consolidation phase and over the first 48 weeks of TFR, but again musculoskeletal pain side effects were more common after treatment discontinuation (14.3 vs 42.1%).

Scores on the MDASI–CML and EQ VAS assessments showed “minimal changes” in patient-reported outcomes “suggesting that stopping and restarting treatment did not substantially alter patients’ overall QOL”, the researchers said.

And patients reported similar numbers of issues on the EQ-5D-5L assessment across the study phases, albeit a higher level of pain or discomfort during TFR than consolidation.

However, Mahon et al discuss the need for “new or adapted tools” to better evaluate QoL in CML patients during TFR after doing well on TKI therapy.

“Further investigation is necessary to evaluate how individual elements of patients’ QOL were impacted by TFR, for example, whether a negative impact of increased pain during TFR was counterbalanced by a positive impact in other areas.”


By Lynda Williams, Senior medwireNews reporter

Meeting website

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