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. 2025 Dec;104(12):6263-6274.
doi: 10.1007/s00277-025-06705-3. Epub 2025 Dec 3.

Outcomes in patients with relapsed/refractory multiple myeloma with extramedullary disease: a meta-analysis

Peter M Voorhees  1 , Shaji Kumar  2 , Saad Z Usmani  3 , Jing Christine Ye  4 , Yael C Cohen  5   6 , Emma Scott  7 , Robin L Carson  7 , Christoph Heuck  7 , Ryan Gan  8 , Benjamin Ackerman  8 , Jenny Zhang  7 , Eleanor Caplan  9 , Trilok Parekh  8 , María-Victoria Mateos  10
Affiliations

Outcomes in patients with relapsed/refractory multiple myeloma with extramedullary disease: a meta-analysis

Peter M Voorhees et al. Ann Hematol. 2025 Dec.

Abstract

Extramedullary disease (EMD), an aggressive form of multiple myeloma (MM), may require a multi-targeted treatment approach rather than standard MM therapies. While precise EMD treatment outcome estimates remain challenging given small clinical trial patient numbers, pooled estimates across studies may increase outcome precision. Meta-regression analyses used Bayesian multilevel, random-effects modeling of patients with and without EMD across nine historical clinical studies of standard treatment regimens, including daratumumab, for relapsed/refractory multiple myeloma (RRMM) from 2013 to 2019. EMD was defined as soft tissue plasmacytomas noncontiguous with bone (“true” EMD). Adjustments were performed to account for differences in baseline age, number of prior lines of therapy (LOT), and International Staging System (ISS) stage. Outcomes included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In patients with EMD (n = 158) versus without EMD (n = 2706), pooled ORR (95% credible interval) was 20.7% (11.7–33.9) versus 66.2% (53.0–77.4) with an odds ratio of 0.13 (0.09–0.20), pooled median PFS was 6.3 (4.2–9.5) versus 12.9 (8.8–18.8) months with a hazard ratio of 1.95 (1.63–2.32), and pooled median OS was 21.0 (15.9–27.9) versus 39.0 (31.0–48.5) months with a hazard ratio of 1.87 (1.53–2.26). Poorer outcomes in patients with versus without EMD were consistent following adjustment for age, number of prior LOT, and ISS stage. These results in patients with RRMM treated with standard treatment regimens confirmed notably worse outcomes in patients with versus without EMD, emphasizing continued unmet clinical need in this patient population.

Supplementary Information: The online version contains supplementary material available at 10.1007/s00277-025-06705-3.

Keywords: Bayesian modeling; Extramedullary disease; Meta-analysis; Meta-regression analysis; Relapsed/refractory multiple myeloma.

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Conflict of interest statement

Declarations. Human ethics and consent to participate: Not applicable. Permission to reproduce material from other sources: Not applicable. Competing interests: P.M.V. has served in a consulting or advisory role for AbbVie, Ascentage Pharma, AstraZeneca, BMS, GSK, Johnson & Johnson, Kite, Pfizer, and Regeneron; and has received research funding from AbbVie, Johnson & Johnson, and Regeneron. S.K. has received research funding from Celgene, Johnson & Johnson, Millennium, Novartis, and Sanofi. S.Z.U. has served in a consulting/advisory role for AbbVie, Amgen, BMS/Celgene, Celgene, Genentech, Gilead Sciences, GSK, Johnson & Johnson, Karyopharm Therapeutics, Merck, and Takeda; and has received research funding from Amgen, Array BioPharma, BMS, Celgene, GSK, Merck, Pharmacyclics, Sanofi, Seattle Genetics, and SkylineDx. J.C.Y. has served in a consulting/advisory role for Bristol Myers Squibb, Johnson & Johnson, and Sanofi; and has received research funding from Celgene, Genmab, GlaxoSmithKline, MingSight, Novartis, Pfizer, and Regeneron. Y.C.C. has received research funding from Amgen, Karyopharm, and Takeda; and has received honoraria or served as a consultant/advisor to Amgen, GSK, Johnson & Johnson, Neopharm/Promedico, and Takeda. E.S. is employed by Johnson & Johnson and has stock/other ownership interests in Johnson & Johnson. R.L.C. is employed by Johnson & Johnson and has stock/other ownership interests in Johnson & Johnson. C.H. is employed by Johnson & Johnson and has stock/other ownership interests in Johnson & Johnson. R.G. was employed by Johnson & Johnson at the time of this analysis and has stock/other ownership interests in Johnson & Johnson. B.A. is employed by Johnson & Johnson and has stock/other ownership interests in Johnson & Johnson. J.Z. is employed by Johnson & Johnson and has stock/other ownership interests in Johnson & Johnson. E.C. is employed by Johnson & Johnson and has stock/other ownership interests in Johnson & Johnson. T.P. is employed by Johnson & Johnson and has stock/other ownership interests in Johnson & Johnson. M.-V.M. has served in a consulting/advisory role for AbbVie, Amgen, Celgene, GlaxoSmithKline, Johnson & Johnson, Pfizer, Regeneron, Roche-Genentech, and Takeda; and has received honoraria from Amgen, AbbVie, Celgene, GlaxoSmithKline, Genentech, Johnson & Johnson, Sanofi, and Takeda.

Figures

Fig. 1
Fig. 1
Estimates of pooled (a) ORR, (b) median PFS, and (c) median OS in patients with RRMM by EMD status, number of prior LOT, and ISS stage. Pooled ORR, pooled median PFS, and pooled median OS were estimated using a random-effects model and stratified by EMD status, number of prior LOT, and by ISS stage. Across all patients, age was held constant to the mean of 64 years. Data points are shown with 95% credible intervals. EMD, extramedullary disease; ISS, International Staging System; LOT, line of therapy; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; RRMM, relapsed/refractory multiple myeloma
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References

    1. Bladé J, Beksac M, Caers J, Jurczyszyn A, von Lilienfeld-Toal M, Moreau P, Rasche L, Rosiñol L, Usmani SZ, Zamagni E, Richardson P (2022) Extramedullary disease in multiple myeloma: a systematic literature review. Blood Cancer J 12:45. 10.1038/s41408-022-00643-3 - DOI - PMC - PubMed
    1. Elbahoty MH, Papineni B, Samant RS (2024) Multiple myeloma: clinical characteristics, current therapies and emerging innovative treatments targeting ribosome biogenesis dynamics. Clin Exp Metastasis 41(6):829–842. 10.1007/s10585-024-10305-2 - DOI - PMC - PubMed
    1. Bladé J, Fernández de Larrea C, Rosiñol L, Cibeira MT, Jiménez R, Powles R (2011) Soft-tissue plasmacytomas in multiple myeloma: incidence, mechanisms of extramedullary spread, and treatment approach. J Clin Oncol 29(28):3805–3812. 10.1200/jco.2011.34.9290 - DOI - PubMed
    1. Liu Y, Jelloul F, Zhang Y, Bhavsar T, Ho C, Rao M, Lewis NE, Cimera R, Baik J, Sigler A, Sen F, Yabe M, Roshal M, Landgren O, Dogan A, Xiao W (2020) Genetic basis of extramedullary plasmablastic transformation of multiple myeloma. Am J Surg Pathol 44(6):838–848. 10.1097/pas.0000000000001459 - DOI - PMC - PubMed
    1. Forster S, Radpour R (2022) Molecular impact of the tumor microenvironment on multiple myeloma dissemination and extramedullary disease. Front Oncol 12:941437. 10.3389/fonc.2022.941437 - DOI - PMC - PubMed

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