Molecular response and quality of life in chronic myeloid leukemia patients treated with intermittent TKIs: First interim analysis of OPTkIMA study

Background: Intermittent treatment with TKIs is an option for the great majority (70%–80%) of CML patients who do not achieve a stable deep molecular response and are not eligible for treatment discontinuation. For these patients, the only alternative is to assume TKI continuously, lifelong. Methods: The Italian phase III multicentric randomized OPTkIMA study started in 2015, with the aim to evaluate if a progressive de-escalation of TKIs (imatinib, nilotinib, and dasatinib) is able to maintain the molecular response (MR^3.0) and to improve Health Related Quality of Life (HRQoL). Results: Up to December 2018, 166/185 (90%) elderly CML patients in stable MR^3.0/MR^4.0 completed the first year of any TKI intermittent schedule 1 month ON and 1 month OFF. The first year probability of maintaining the MR^3.0 was 81% and 23.5% of the patients who lost the molecular response regained the MR^3.0 after resuming TKI continuously. Patients’ HRQoL at baseline was better than that of matched peers from healthy population. Women was the only factor independently associated with worse baseline HRQoL (p > 0.0001). Overall, global HRQoL worsened at 6 (p < 0.001) but returned to the baseline value at 12 months and it was statistically significantly worse in women (p = 0.001). Conclusions: De-escalation of any TKI by 1 month ON/OFF schedule maintains the MR^3.0/MR^4.0 in 81% of the patients during the first 12–24 months. No patients progressed to accelerated/blastic phase, all the patients (23.5%) losing MR^3.0 regained the MR^3.0 and none suffered from TKI withdrawn syndrome. The study firstly report on HRQoL in elderly CML patients moving from a continuous daily therapy to a de-escalated intermittent treatment.