The addition of mesenchymal stromal cells (MSC) to basiliximab and a calcineurin inhibitor improved outcomes among patients with steroid-refractory, acute graft vs host disease (aGVHD) after hematopoietic stem cell transplant, according to the results of a phase 3 study published in the Journal of Hematology & Oncology.
Although MSCs are recommended as a second-line treatment for aGVHD, “not enough data from well-designed randomized controlled trials are available to verify the second-line treatment position of MSCs for aGVHD,” the authors wrote.
This multicenter, open-label, phase 3 trial randomly assigned 198 patients with steroid-refractory aGVHD to receive basiliximab plus a calcineurin inhibitor with or without MSCs. The primary endpoint was overall response (OR), and secondary endpoints included failure-free survival (FFS), overall survival (OS), chronic GVHD (cGVHD), and safety.
At baseline, the median age was 29 and the majority of patients received a hematopoietic transplant to treat acute myeloid leukemia or acute lymphoblastic leukemia. Human leukocyte antigen (HLA) was matched among 51.5% of patients and peripheral blood stem cells was the donor source for 55.6%.
The addition of MSCs significantly increased the OR. At 28 days, the OR was 82.8% with MSCs compared with 70.7% without MSCs (odds ratio, 2.00; 95% CI, 1.01-3.94; P =.043). The greatest benefit was observed among patients with grade IV aGVHD and those with more than 2 organs involved.
At 56 days, the OR was 78.8% and 64.6% with or without MSCs, respectively (odds ratio, 2.02; 95% CI, 1.08-3.83; P =.027).
FFS was also longer with MSCs, with a median of 11.3 months compared to 6.0 months without MSCs (hazard ratio [HR], 0.68; 95% CI, 0.48-0.95; P =.024). Although there was a trend toward improved OS with the addition of MSCs, the difference was not significant (HR, 0.67; 95% CI, 0.43-1.02; P =.060).
cGVHD was less likely to occur among patients treated with MSCs, with a 2-year cumulative incidence of 39.5% compared with 62.7% without MSCs (HR, 0.55; 95% CI, 0.36-0.84; P =.005).
Overall, patients treated with MSCs experienced fewer any grade and grade 3 or higher adverse events, including serious adverse events. MSCs also reduced the incidence of grade 3-4 infections, with a rate of 65.7% and 78.8%, respectively, within 180 days after treatment. Hematologic toxicity was also lower, occurring among 37.4% of patients with MSCs and 53.5% of patients not treated with MSCs.
The rate of tumor relapse was similar between the study groups. The authors concluded that these data suggest “MSCs could be recommended as a second-line treatment option for aGVHD patients.”
Zhao K, Lin R, Fan Z, et al. Mesenchymal stromal cells plus basiliximab, calcineurin inhibitor as treatment of steroid‑resistant acute graft‑versus‑host disease: a multicenter, randomized, phase 3, open‑label trial. J Hematol Oncol. 2022;15:22. doi: 10.1186/s13045-022-01240-4