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MULTIPLE MYELOMA, GAMMOPATHIES

Urine-free response criteria predict progression-free survival in multiple myeloma: a post hoc analysis of BMT CTN 0702

Leukemia volume 39, pages 1001–1004 (2025)Cite this article

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International Myeloma Working Group (IMWG) response criteria for multiple myeloma (MM) currently involve a combination of blood-based, urine-based, and marrow-based assessments [1]. Unlike blood-based assays which can be obtained from a single venipuncture, urine testing in MM requires that every urinary void over a 24-h period be collected. Collecting and storing all urinary voids can be difficult for patients with underlying frailty, treatment-related neuropathy, or unreliable access to refrigeration [2, 3]. Additionally, fewer than 1% of patients with plasma cell disorders have Bence-Jones proteinuria quantifiable on urine protein electrophoresis (UPEP) in the absence of abnormalities on serum protein electrophoresis (SPEP), serum immunofixation (SIFE), or serum free light chain (SFLC) testing [4]. In the real-world setting, fewer than a third of patients with MM undergo 24-h UPEP testing at diagnosis [5]. Several post hoc analyses of Phase 3 trials have demonstrated that the prognostic impact of 24-h urine immunofixation (UIFE) on progression-free survival (PFS) is negligible compared to that of SFLC assays or bone marrow plasma cell burden [6, 7].

The broader practicality of removing urine assessments from response criteria entirely has only been investigated once to our knowledge (Table 1) [3]. Adopting urine-free criteria led to changes in response depths for only 4% of patients in this small single-center analysis; however, the impact of these changes on PFS was not evaluated. To answer this more important question, we conducted an unplanned post hoc analysis of patients with MM enrolled in the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0702 (STaMINA) trial of treatment strategies following autologous stem cell transplantation (ASCT) (clinicaltrials.gov ID: NCT01109004). This trial demonstrated no intent-to-treat differences in PFS or overall survival between standard maintenance, post-ASCT consolidation, and tandem transplantation [8]. We pooled patient data from all study arms, including patients who did not complete their planned treatment strategies. We analyzed responses at the Day +56 timepoint following ASCT (first ASCT if patients underwent tandem transplantation), which was the first timepoint for response assessments. Patients who were non-evaluable for urine-free responses (as defined below) or who had progressive disease (PD) at this initial timepoint were excluded. Response assessments relative to diagnosis were calculated as stable disease (SD), partial response (PR), very good partial response (VGPR), or complete response (CR) [1]. To simplify comparisons, minimal responses were classified as SD and stringent complete responses as CR.

Table 1 Schema of traditional versus urine-free response criteria.
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Fig. 1: Progression-free survival based on each set of criteria.

Data availability

Available from the corresponding author upon reasonable request.

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Acknowledgements

We wish to acknowledge the patients who participated in the BMT CTN 0702 trial as well as the research personnel at all study sites.

Funding

Support for this study was provided by grants #U10HL069294 and #U24HL138660 to the Blood and Marrow Transplant Clinical Trials Network from the National Heart, Lung, and Blood Institute and the National Cancer Institute along with contributions by Celgene Corporation and Millennium Pharmaceuticals, Inc., funding by The Alliance for Clinical Trials in Oncology, the ECOG-ACRIN Cancer Research Group and SWOG. The content is solely the responsibility of the authors and does not necessarily represent the official views of the above-mentioned parties.

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Authors and Affiliations

  1. Fred Hutchinson Cancer Center, Seattle, WA, USA

    Rahul Banerjee & Andrew J. Cowan

  2. University of Washington, Seattle, WA, USA

    Rahul Banerjee & Andrew J. Cowan

  3. The Emmes Company, Rockville, MD, USA

    Amber R. Fritz & Adam Mendizabal

  4. Medical College of Wisconsin, Milwaukee, WI, USA

    Othman S. Akhtar & Marcelo C. Pasquini

  5. Moffitt Cancer Center, Tampa, FL, USA

    Ciara L. Freeman

  6. University of California San Francisco, San Francisco, California, USA

    Nina Shah

  7. Memorial Sloan Kettering Cancer Center, New York City, NY, USA

    Heather J. Landau

  8. Mayo Clinic, Rochester, MN, USA

    Shaji K. Kumar

  9. University of Pennsylvania, Abramson Cancer Center, Philadelphia, PA, USA

    Dan T. Vogl & Edward A. Stadtmauer

  10. OhioHealth Blood and Marrow Transplant, Columbus, OH, USA

    Yvonne A. Efebera

  11. Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA

    Philip L. McCarthy

  12. John Theurer Cancer Center, Hackensack, NJ, USA

    David H. Vesole

  13. City of Hope Cancer Center, Duarte, CA, USA

    Amrita Y. Krishnan & George Somlo

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  1. Rahul Banerjee
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Contributions

RB, ARF, OSA, and CLF analyzed the data and contributed to the first draft of the manuscript. AJC, NS, HJL, SKK, DTV, YAE, PLM, DHV, AM, AYK, GS, EAS, MCP contributed patients to this analysis, provided critical feedback to several drafts, and approved of the final manuscript.

Corresponding author

Correspondence to Rahul Banerjee.

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Competing interests

RB reports: consulting, Adaptive Biotech, BMS, Caribou Biosciences, Genentech, Gilead, Janssen, Karyopharm, Legend Biotech, Pfizer, Sanofi, SparkCures; Research: Abbvie, BMS, Janssen, Novartis, Pack Health, Prothena, Sanofi. CLF reports: honoraria/consulting for BMS, Seattle Genetics, Celgene, Abbvie, Sanofi, Incyte, Amgen, and ONK therapeutics, Janssen; research funding from BMS, Janssen and Roche/Genentech. AJC reports research funding: Janssen, BMS, Juno/Celgene, Sanofi, Regeneron, IGM biosciences, Nektar, Harpoon, Adaptive Biotechnologies, Caelum, Abbvie; advisory/consulting: Sebia, Janssen, BMS, Sanofi, HopeAI, Adaptive Biotechnologies, Abbvie. NS reports: research funding from Bristol Myers Squibb/Celgene, Janssen, bluebird bio, Sutro Biopharma, TeneoBio, Poseida, Nektar, and Precision Biosciences; consultant for GSK, Amgen, Indapta Therapeutics, Sanofi, CareDx, Kite, Karyopharm Therapeutics, Oncopeptides, and CSL Behring; current employee and equity holder of AstraZeneca. HJL reports: consulting, Abbvie, Immix Biopharma, Legend Biotech, Alexion, Prothena; funding: Janssen, Alexion, Protego, Prothena. SKK reports: funding: Abbvie, Celgene, Janssen, Takeda, Adaptive, Kite, AstraZeneca, Merck, Novartis, Roche, Sanofi. D.T.V. reports: consulting, Celgene, Karyopharm Therapeutics, Janssen, Takeda, GlaxoSmithKline, CSL Behring, Oncopeptides, Genentech, Sanofi; research funding, Active Biotech, Takeda. YAE reports: research funding, Takeda, Oncopeptides, Alnylam, Sanofi, GlaxoSmithKline, ORCA Therapeutics, BMS; consulting: Oncopeptides, Sanofi, Janssen Oncology, Pfizer, speaker’s bureau: Takeda, Janssen, Akcea Therapeutics. PLM reports: consulting: Beigene, BMS/Celgene/Juno, Fate Therapeutics, Glaxo Smith Klein, JnJ (Janssen), Karyopharm, Meda Consulting. D.H.V. reports: speaker’s bureau: BMS, Amgen, Takeda, Janssen, Sanofi, Karyopharm, Sanofi. AYK reports: consulting: AbbVie, Bristol Myers Squibb, GSK, JnJ, Pfizer, Regeneron, Sanofi; research funding: JnJ, Roche; speaker’s bureau: BMS, Takeda; stock options: BMS. EAS reports: consulting: Celgene, Takeda, Novartis, Teva, Janssen, Amgen, Sanofi. MCP reports: consulting: BMS; research: Novartis, Janssen, Kite. The remaining authors have no conflicts to disclose.

Ethics approval and consent to participate

All methods and study procedures. were performed in accordance with relevant guidelines and regulations. Every participating center in the BMT CTN 0702 trial obtained Institutional Review Board approval for the original study from which data were obtained for this post hoc analysis. Similarly, all study participants provided informed consent for participation in the BMT CTN 0702 trial. No identifiable information was obtained as part of this post hoc analysis.

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Banerjee, R., Fritz, A.R., Akhtar, O.S. et al. Urine-free response criteria predict progression-free survival in multiple myeloma: a post hoc analysis of BMT CTN 0702. Leukemia 39, 1001–1004 (2025). https://doi.org/10.1038/s41375-025-02534-5

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