Quality-of-life endpoints collection, reporting, and framing in randomised trials of indolent lymphomas: a systematic review

Indolent lymphomas are generally incurable, with protracted disease courses. The approval of drug treatment options often relies on surrogate endpoints (eg, progression-free survival), which do not capture patient-centred outcomes such as quality of life (QOL). This systematic review characterises the use of QOL as an endpoint in randomised controlled trials (RCTs) of indolent lymphomas, and the association of QOL with survival outcomes. ClinicalTrials.gov was searched from database inception to May 20, 2024, for phase 3 RCTs of indolent lymphomas, including follicular lymphoma, marginal zone lymphoma, chronic lymphocytic leukaemia or small lymphocytic lymphoma, gastric mucosa-associated lymphoid tissue lymphoma, and Waldenstr & ouml;m macroglobulinaemia. 103 RCTs met eligibility criteria. Data on QOL endpoints were collected in 53 (51%) of 103 trials, but reported in only 25 (24%). Improvements in QOL was reported in 11 (44%) of these RCTs, and these trials were more likely to show progression-free survival and overall survival benefits. We found that trials with neutral or worsened QOL outcomes often framed the results positively, presenting QOL data as supporting treatment use. This systematic review highlights that data on QOL endpoints are undercollected, under-reported, and often positively framed despite a lack of improvement, underscoring the need for transparent QOL reporting to enhance patient-centred care.