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. 2025 Oct;25(10):730-738.e11.
doi: 10.1016/j.clml.2025.03.013. Epub 2025 Apr 3.

Ranking the Importance of Prognostic Factors for Relapsed/Refractory Multiple Myeloma: International Physician Panel Consensus Following a Systematic Literature Review

Shaji Kumar  1 , Xavier Leleu  2 , Katja C Weisel  3 , Rakesh Popat  4 , Beatrice Suero  5 , Samantha Craigie  5 , Paul Spin  5 , Leena Patel  5 , Abril Oliva Ramirez  5 , Christian Hampp  6 , Wenzhen Ge  6 , Qiufei Ma  6 , Sundar Jagannath  7
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Free article

Ranking the Importance of Prognostic Factors for Relapsed/Refractory Multiple Myeloma: International Physician Panel Consensus Following a Systematic Literature Review

Shaji Kumar et al. Clin Lymphoma Myeloma Leuk. 2025 Oct.
Free article

Abstract

Purpose: The increasing use of single-arm and nonrandomized trial designs in oncology aims to expedite patient access to novel treatments. To contextualize their results using strategies such as external control arms or indirect treatment comparisons, prespecification of, and subsequent adjustment for, prognostic factors is required to ensure comparability of populations and avoid bias. This study aimed to systematically identify and rank prognostic factors relevant to treatment outcomes in patients with relapsed/refractory multiple myeloma (RRMM).

Materials and methods: To comprehensively identify prognostic factors, a systematic literature review was conducted with databases searched between January 2016 and April 2022. Clinical studies enrolling adult patients with RRMM and assessing prognostic significance using adjusted analyses were included. Subsequently, an international panel of multiple myeloma experts confirmed and ranked these variables by their importance in predicting clinical outcomes. A structured series of expert consultations was conducted from November 2022 to February 2023, including 2 rounds of consensus meetings.

Results: Of 125 studies included in the systematic literature review, 112 described 97 factors significantly associated with at least 1 outcome of interest. A total of 25 factors associated with overall survival and/or objective response and reported in at least 2 studies were included in the ranking process. The physician panel unanimously agreed on the 6 most important prognostic factors: cytogenetic risk, age, refractory status, disease stage, performance status, and extramedullary disease/plasmacytoma.

Conclusion: This list of RRMM prognostic factors can be used in comparative analyses to assess treatment effectiveness in the absence of head-to-head trials.

Keywords: Real-world data; Relapsed or refractory; Systematic review.

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Conflict of interest statement

Disclosure BS, SC, PS, LP, and AOR are employees of EVERSANA, Canada, which received funds from Regeneron Pharmaceuticals, Inc., for this work. CH, WG, and QM are employees and shareholders of Regeneron Pharmaceuticals, Inc.

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