Systematic review reveals urgent need to homogenize endpoints choices and definitions in marginal zone lymphomas trials

Abstract

Marginal zone lymphoma (MZL) is a heterogeneous disease and has various end-point measures. Our aim was to describe the endpoints used in trials involving patients with MZL. We searched over the last 35 years via PubMed, The Cochrane Library, clinicaltrials.govandclinicaltrialsregister.eu for published and registered clinical trials using the keyword “marginalzone lymphoma.” We excluded studies focusing on pediatric populations, cutaneous MZL and on use of allogenic stem cell transplant. Endpoints were reviewed as well as their influencing factors and their definitions. Among 1192 references Q7 dentified by initial screening, 309 references were included (111 published, 198 registered), with 213 (69%) phase 2, 65 (21%) phase 1/2 and 31 (10%) phase 3 trials. The majority were open-label (n¼295, 95%) non-randomized (n¼256, 83%) trials, concerned all subtypes of MZLs at once (n¼239, 77%), and were often merged with non-MZL patients (n¼232, 75%). Among phase 1/2 and 2 trials, Overall/complete response rate (ORR/CRR) (n¼196, 70.5%) and progression-free survival (PFS,n¼28, 10.1%) were the most used primary endpoints; in phase 3 trials PFS was the most used primary endpoint (n¼18, 58.1%; ORR/CRR n¼6, 19.4%, p<0.001). Overall, the most frequent secondary endpoints were overall survival (OS, n¼153, 50%), PFS (n¼142, 46%) and ORR/CRR (n¼116, 38%). Distribution was similar when considering trials with only patients with MZL. Endpoints definitions were inconsistent across published trials (up to 9 definitions per endpoint). Trials involving patients with MZL showed marked heterogeneity both in the choice and definitions of primary and secondary endpoints, thus hampering comparability between trials.

Keywords:

• Marginal zone lymphoma
• endpoints
• systematic review
• definitions
• indolent lymphoma

Acknowledgments

We sincerely thank Prof. Sylvie Chevret, Ph.D., for her benevolent proofreading.

Ethics statement

Research on research does not include human individuals and thus does not require consent from any participant.

Author contributions

C.B., J.L. and C.T. conceived of the presented idea and developed the methodology. C.B., M.R., A.M. and J.L. screened and reviewed the references. C.B. analyzed the data. J.L., E.Z. and C.T. supervised the findings of the work. All authors discussed the results and contributed to the final manuscript.

Prior presentations

Preliminary results of this work have been presented during the poster session at the 2021 International Conference on Malignant Lymphoma (16-ICML).

Disclosure statement

Authors declare no conflicts of interest related to this work.

Data availability statement

The data underlying this article are available online. Data resulting from extraction will be shared on reasonable request to the corresponding author.

Additional information

Funding

First author of this research paper is funded by a public grant from Agence Régionale de Santé Île-de-France as part of a PhD graduation. Agence Régionale de Santé Île-de-France had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.