Retrospective comparison of mesenchymal stromal cells and antithymocyte globulin as second-line therapy for acute graft-versus-host disease.

As a second-line treatment for first-line steroid-refractory acute GVHD, ruxolitinib was proven to be significantly more effective than control therapies (nine commonly used therapy options) in a prospective, randomized trial. However, it could sometimes be difficult to administer ruxolitinib for patients with cytopenia or who have difficulty taking it orally regularly. The present retrospective study compared the outcomes of second-line mesenchymal stromal cell (MSC) and antithymocyte globulin (ATG) therapies following first-line steroid therapy for acute GVHD. Clinical data for the total 1120 patients who received MSC (n = 777) and ATG (n = 343) as second-line therapy following first-line steroid therapy for acute GVHD from 2016 to 2022, when both therapies were covered by health insurance in Japan, were extracted from Japanese stem cell transplantation registry data. Overall response rates (ORRs) on day 28 of the MSC and ATG therapies were 62.7% and 51.0%, respectively (multivariate analysis: odds ratio, 1.56; P = 0.001). ORRs for skin, liver, and gastrointestinal tract acute GVHD were 66.3% versus 57.5% (1.43, P = 0.063), 33.1% versus 25.7% (1.18, P = 0.636), and 66.3% versus 49.8% (1.96, P < 0.001), respectively. The incidences of invasive fungal infection and viral infection within the first 100 days after the start of second-line therapy were 3.9% versus 8.2% (Fisher's exact test: P = 0.005) and 13.4% versus 25.1% (P < 0.001), respectively. However, non-relapse mortality, the relapse rate, and overall survival did not differ between MSC and ATG therapies. Furthermore, the propensity score-matched analysis yielded results consistent with the findings described above. In conclusion, this retrospective study demonstrated that the ORR based on whole body assessment and the ORR based on gastrointestinal tract stage assessment were both significantly higher with MSC therapy than with ATG therapy. However, prospective, randomized, controlled trials are necessary for a more accurate comparison.