Background: Indolent lymphomas are incurable malignancies with extended disease courses and prolonged overall survival (OS). This longevity poses challenges for clinical trial design, particularly in selecting meaningful, patient-centered endpoints. While OS and progression-free survival (PFS) are commonly used, our prior work demonstrates that PFS has only a weak correlation with OS in follicular lymphoma (FL). Quality of life (QoL), a critical consideration in therapeutic decision making for patients and clinicians, remains underutilized despite its relevance. Unlike survival endpoints, QoL data are not currently incentivized in regulatory pathways for drug approval. We sought to examine whether trial sponsorship type influences the collection and reporting of QoL endpoints in randomized trials for indolent lymphoma.

Methods: We conducted a systematic search of trials in indolent lymphoma using ClinicalTrials.gov, using the terms “marginal zone lymphoma,” “mantle cell lymphoma,” “follicular lymphoma,” “indolent lymphoma,” “B cell lymphoma,” “Non-Hodgkin lymphoma,” “small lymphocytic lymphoma,” “mucosa-associated lymphoid tissue lymphoma,” and “Waldenstrom” in the disease field. We included completed Phase III trials in our search, with statuses “active, not recruiting,” “completed,” and “terminated.” Trials with statuses “not yet recruiting,” “recruiting,” “enrolling by invitation,” “suspended,” “withdrawn,” or “unknown” were excluded. Trials were eligible for inclusion if they reported survival outcomes in peer-reviewed journals. These trials were screened for incorporation of QoL endpoints using ClinicalTrials.gov information and by a PubMed search. Trials were characterized as those that reported, collected but did not report, or did not collect QoL data. Sponsorship was identified by sponsor type listed on ClinicalTrials.gov.

Results: 102 trials met inclusion criteria. Disease subtypes included chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in 48 trials (47.1%), FL in 21 (20.6%), grouped indolent lymphoma in 21 (20.6%), mantle cell lymphoma (MCL) in 7 (6.86%), Waldenström macroglobulinemia (WM) in 4 (3.92%), and MALT lymphoma in 1 trial (0.980%). Sponsor types were categorized as industry-sponsored, which accounted for 61 trials (59.8%) and non-industry-sponsored, which described 41 trials (40.2%); the latter category included cooperative group-sponsored trials and multicenter grant-sponsored trials.

Overall, QoL endpoints were collected in 53 trials (52.0%) and reported in only 25 (24.5%). Rates of QoL reporting were 18/61 (29.5%) in industry-sponsored trials compared to 7/41 (17.1%) in non-industry-sponsored trials. For trials that collected but did not report QoL data, rates were similar by sponsor type with 17/61 (27.9%) industry trials and 11/41 (26.8%) non-industry trials. For trials that did not collect QoL data at all, rates varied slightly between sponsor type with 26/61 (42.6%) industry trials and 23/41 (56.1%) non-industry trials not collecting data.

Chi-square testing showed no statistically significant differences in QoL data collection or reporting patterns between sponsor types. There were no significant differences in QoL reporting between industry and non-industry-sponsored trials, χ2 (1, N=102) =2.05, p=0.152. However, there are notable absolute differences in reporting between industry and non-industry-sponsored trials.Conclusions: Across all sponsor types, QoL data were infrequently reported in randomized trials of indolent lymphoma—even when collected. These findings underscore a persistent gap in patient-centered outcomes reporting and point to a need for standardized integration of QoL metrics into clinical trial design. Given the chronic nature of indolent lymphoma and the impact of treatment on long-term well-being, QoL should be universally collected and transparently reported to better inform shared decision-making and therapeutic value assessment. Although industry-sponsored trials appeared more likely to collect or report QoL data than cooperative group and multicenter grant-sponsored trials, this trend did not reach statistical significance, potentially due to limited sample size. Future work with larger datasets may further clarify differences between sponsor types and reinforce the importance of QoL in regulatory and clinical decision-making.

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2025
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