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Mesenchymal stromal cell therapy induces high responses and survival in children with steroid refractory GVHD and poor risk biomarkers

Bone Marrow Transplantation volume 56, pages 2869–2870 (2021)Cite this article

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Remestemcel-L is comprised of culture-expanded mesenchymal stromal cells (MSCs) derived from the bone marrow of an unrelated donor and under investigation as treatment for graft-vs-host disease (GVHD). A phase 3 multicenter single-arm study (NCT02336230) of 54 children with steroid refractory (SR) GVHD treated with remestemcel-L as second-line therapy has recently been reported [1]. Here we report the analyses of the Mount Sinai Acute GVHD International Consortium (MAGIC) Algorithm Probability of 25 of the 54 pediatric study patients with serum samples taken at the beginning of treatment and compare them to 27 closely matched pediatric patients with SR acute GVHD who participated in a prospective GVHD natural history study. Control patients were included if they met the remestemcel-L study criteria for GVHD severity at the time they received second-line therapy and had serum samples available when second-line therapy was initiated. All biomarker assays were conducted by investigators blinded to clinical outcomes.

The MAGIC Algorithm Probability (MAP) combines the serum concentrations of two biomarkers, Reg3α and ST2, into a single value that predicts long-term outcomes such as response to therapy after 28 days and 6-month non-relapse mortality (NRM) [3]. The MAP is an accurate monitoring biomarker of GVHD in the GI tract and is considered a “liquid biopsy” of crypt damage [4]. MAPs ≥0.291 predict high NRM and poor responses to therapy in SR acute GVHD [5]. We measured the serum concentrations of Reg3α and ST2 by ELISA and calculated the MAP for all 52 patients. At baseline the mean MAPs were similar between the study patients treated with remestemcel-L vs MAGIC controls (0.283 ± 0.17 vs 0.262 ± 0.20, p = 0.67). In all, 48% (12/25) remestemcel-L study patients and 37% (10/27) of MAGIC control patients were high risk by baseline MAP ≥ 0.291. One remestemcel-L patient was lost to follow-up and excluded from the survival analysis. As shown in Fig. 1B, survival at day +180 was significantly better for patients with a high-risk MAP treated with remestemcel-L compared to high-risk control patients who received best available therapy (7/11, 64% vs 1/10, 10%, p = 0.01). Consistent with these survival results, 8/12 study patients treated with remestemcel-L, who were high risk by biomarkers, achieved a clinical response by day 28 of remestemcel-L therapy, compared to 1/10 MAGIC patients who received the best available treatment (67% vs 10%, p = 0.01).

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Fig. 1: Baseline characteristics and 6-month survival of SR acute GVHD patients according to treatment.

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Funding

National Cancer Institute (P01CA039542 and P30CA196521), the Pediatric Cancer Foundation, and Mesoblast provided funding for this study.

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  1. These authors contributed equally: John E. Levine, James L. M. Ferrara.

Authors and Affiliations

  1. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Stelios Kasikis, Janna Baez, Isha Gandhi, Steven Kowalyk, George Morales, Rachel Young, John E. Levine & James L. M. Ferrara

  2. Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Stephan Grupp

  3. Vanderbilt University Medical Center, Nashville, TN, USA

    Carrie L. Kitko

  4. Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Pediatrico Bambino Gesù, Rome, Italy

    Pietro Merli

  5. Section of Transplantation and Cellular Therapy, Children’s Hospital Los Angeles, Los Angeles, CA, USA

    Michael A. Pulsipher

  6. Aflac Cancer and Blood Disorders Center, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA, USA

    Muna Qayed

  7. Children’s Hospital, University of Würzburg, Würzburg, Germany

    Matthias Wölfl

  8. University of Michigan, Ann Arbor, MI, USA

    Gregory Yanik

  9. Mesoblast, Inc., New York, NY, USA

    Fiona See, Jack Hayes, Fred Grossman & Elizabeth Burke

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  1. Stelios Kasikis
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Correspondence to James L. M. Ferrara.

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Competing interests

FS, JH, FG and EB are employees of Mesoblast. JEL and JLMF have received consulting fees from Mesoblast and royalties from a GVHD biomarker patent.

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Kasikis, S., Baez, J., Gandhi, I. et al. Mesenchymal stromal cell therapy induces high responses and survival in children with steroid refractory GVHD and poor risk biomarkers. Bone Marrow Transplant 56, 2869–2870 (2021). https://doi.org/10.1038/s41409-021-01442-3

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