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Time-to-event surrogate end-points in multiple myeloma randomised trials from 2005 to 2019: a surrogacy analysis
Umeå University, Faculty of Medicine, Department of Radiation Sciences.ORCID iD: 0000-0001-8308-0373
Division of Hematological Malignancies and Cellular Therapeutics, University of Kansas, KS, Lawrence, United States.
Division of Hematology and Hematological Malignancies, University of Utah, UT, Salt Lake City, United States.
Division of Hematology and Hematological Malignancies, University of Utah, UT, Salt Lake City, United States.
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2023 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 200, no 5, p. 587-594Article in journal (Refereed) Published
Abstract [en]

Use of surrogate end-points such as progression-free survival (PFS) and other time-to-event (TTE) end-points is common in multiple myeloma (MM) clinical trials. This systematic review characterises all published randomised controlled trials (RCTs) in MM using PFS or other TTE end-points between 2005 and 2019 and assesses strength of surrogacy of PFS for overall survival (OS). The association between OS hazard ratios (HRs) and PFS HRs was evaluated with linear regression, and the coefficient of determination with Pearson's correlation. We identified 88 RCTs of which 67 (76%) used PFS as the primary/co-primary end-point. One trial indicated whether progression was biochemical or clinical. Of the variance in OS, 39% was due to variance in PFS. Correlation between PFS and OS was weak (0.62, 95% confidence interval [CI] 0.38–0.78). In newly diagnosed MM, 43% of the variance in OS was due to changes in PFS. The correlation between PFS and OS was weak (0.65, 95% CI 0.30–0.84). In relapsed/refractory MM, 58% of the variance in OS was due to changes in PFS. Correlation between PFS and OS was medium (0.76, 95% CI 0.42–0.91). We demonstrate that PFS and progression characteristics are characterised poorly in MM trials and that PFS is a poor surrogate for OS in MM.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023. Vol. 200, no 5, p. 587-594
Keywords [en]
end-point, multiple myeloma, overall survival, progression-free survival, randomised controlled trial
National Category
Hematology Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-202019DOI: 10.1111/bjh.18568ISI: 000895964200001PubMedID: 36495317Scopus ID: 2-s2.0-85148325670OAI: oai:DiVA.org:umu-202019DiVA, id: diva2:1722468
Note

First published online: 10 December 2022

Available from: 2022-12-29 Created: 2022-12-29 Last updated: 2023-03-24Bibliographically approved

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Etekal, Tommy

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