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Increased CXCL10 is seen at 1-year after autologous hematopoietic cell transplantation in multiple myeloma patients on maintenance lenalidomide therapy

Bone Marrow Transplantation volume 58, pages 953–955 (2023)Cite this article

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Compared to healthy controls, patients with multiple myeloma (MM) have significant and persistent dysregulation of cytokines, including IL-2, IL-6, IL-8, and TNF-α [1]. Serum TNF-α [2] and IFN-γ induced protein-10 (or CXCL10) [3] have been associated with worse disease and/or symptom burden. Health-related quality of life (QOL) and symptom burden are important outcomes in MM patients on treatment. Autologous hematopoietic cell transplantation (AHCT) is associated with symptom burden with serum IL-6 correlating with symptom burden early post-transplant [4] while serum TNF-α predicts symptom burden 3–9 months post-AHCT [5]. We sought to understand changes in cytokines and associations with symptom burden in MM patients after 1-year post-AHCT in patients on maintenance therapy and in response. Identifying such relationships can aid in the mechanistic understanding of symptom burden and have the potential for biomarker-focused therapeutic interventions to improve QOL in MM.

We recently described the long-term post-AHCT QOL recovery in MM patients treated on the BMT CTN 0702 (STaMINA) trial, identifying that up to 62% of patients with moderate or greater burden for at least one symptom at 1-year post-AHCT [6]. In this exploratory analysis, we studied cytokine and QOL correlations in patients who had available serum samples and FACT-BMT assessments pre-AHCT and 1-year after AHCT (N = 232). The STaMINA trial compared progression-free and overall survival among 758 MM patients randomized to one of three treatments after AHCT: (1) second AHCT followed by lenalidomide maintenance (n = 247); (2) consolidation with lenalidomide/bortezomib/dexamethasone followed by lenalidomide maintenance (n = 254); or (3) lenalidomide maintenance (n = 257). The primary analysis revealed similar clinical outcomes, including in QOL scores measured using FACT-BMT and SF-36, in all three arms [7].

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Funding

This ancillary study was funded by a Froedtert & MCW Cancer Center grant (project 3379013). Dr. D’Souza is supported by K23 HL141445. The work of SJ was supported in part by NCI R01CA236814, the William G. Schuett, Jr., Multiple Myeloma Research Endowment, and the Riney Family Multiple Myeloma Research Initiative. MBD is supported in part by a grant from the National Cancer Institute, R01 CA226279, and continuing philanthropic support from the Hanis-Stepka-Rettig Endowed Chair in Cancer Research and the Bobbie Nick Voss Charitable Foundation. The BMT CTN 0702 was supported by Grant No. 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; by Celgene Corporation and Millennium (Takeda) Pharmaceuticals; and by The Alliance for Clinical Trials in Oncology, the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group, and SWOG. The content of this article is solely the responsibility of the authors and does not represent the official views of the funding parties.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

    Meera Mohan, Siegfried Janz, Jing Dong, Marcelo C. Pasquini & Anita D’Souza

  2. Division of Biostatistics, Institute of Health and Equity, Medical College of Wisconsin, Milwaukee, WI, USA

    Ruta Brazauskas & Bi Qing Teng

  3. Center for Immunology, Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, WI, USA

    Michael B. Dwinell

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

    Grant Yun

  5. Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Sergio Giralt & Heather Landau

  6. Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Edward Stadtmauer

  7. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Cancer Center, Duarte, CA, USA

    Amrita Krishnan

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  1. Meera Mohan
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Contributions

MM reviewed the analysis and wrote the first draft of the manuscript. RB and BQT designed and conducted the biostatistical analysis and edited the manuscript. GY and SJ conducted the cytokine assays, reviewed the analysis, and edited the manuscript. JD and MBD reviewed the analysis and edited the manuscript. MCP (Protocol Officer, BMT CTN 0702), SG, HL, EAS (Protocol Co-Chair, BMT CTN 0702), and AK (Protocol Co-Chair, BMT CTN 0702) led the BMT CTN 0702 study and/or were from the top 3 centers that provided data contributing to this study, reviewed the current analysis, and edited the manuscript. All authors approved the final manuscript draft. AD designed the study, obtained funding, reviewed the analysis, and edited the manuscript.

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Correspondence to Anita D’Souza.

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Competing interests

MM reports institutional research funding from GlaxoSmithKline, Takeda Pharmaceutical Company, Ionis Pharmaceuticals, Bristol-Myers Squibb (BMS), Celgene Corporation and Amgen Inc.; Advisory board fees: Sanofi. MBD is a co-founder and has ownership and financial interests in Protein Foundry, LLC and Xlock Biosciences, LLC. MCP has research support from BMS, Kite Pharma, Janssen, and Novartis and consultancy fees from BMS. SG reports research funding from Amgen, Actinium, Celgene, Johnson & Johnson, Miltenyi, Takeda, Omeros and advisory board for Amgen, Actinium, Celgene, Johnson & Johnson, Janssen, JAZZ Pharmaceutical, Takeda, Novartis, Kite, and Spectrum Pharma. HL reports research funding from Takeda, advisory board fees from Takeda, Pfizer, Janssen, Celgene, Genzyme, Caelum, honorarium from Pfizer and Genzyme. ES reports research funding and consultancy fees from BMS. AK reports research funding from Janssen, SAB Sutro, speaker fees from BMS, Glaxo Smith Kline (GSK), and Takeda, consulting fees from BMS, Janssen, Adaptive, Sanofi, Pfizer, Regeneron, Abbvie, and GSK. AD reports institutional research funding from Abbvie, Caelum, Janssen, Novartis, Prothena, Regeneron, Takeda, consulting fees from Janssen and Prothena, advisory board fees from BMS, Janssen, Kedrion, and Prothena. RB, SJ, BQT, GY, and JD have no conflicts to report.

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Mohan, M., Janz, S., Brazauskas, R. et al. Increased CXCL10 is seen at 1-year after autologous hematopoietic cell transplantation in multiple myeloma patients on maintenance lenalidomide therapy. Bone Marrow Transplant 58, 953–955 (2023). https://doi.org/10.1038/s41409-023-02004-5

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