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Health-related quality of life in patients with steroid-refractory acute graft-versus-host disease
Leeneman, B., Blommestein, H. M., van Dongen-Leunis, A., Algeri, M., Fibbe, W. E., Oosten, L., Uyl-de Groot, C. A., Thielen, F. W.
European journal of haematology. 2023
Abstract
BACKGROUND Evidence regarding health-related quality of life (HRQoL) in patients with steroid-refractory acute graft-versus-host disease (SR-aGvHD) is lacking. Evaluating HRQoL was a secondary objective of the HOVON 113 MSC trial. Here we describe the outcomes of the EQ-5D-5L, EORTC QLQ-C30, and FACT-BMT for all adult patients who completed these questionnaires at baseline (i.e., before the start of treatment; n = 26). METHODS Descriptive statistics were used to describe baseline patient and disease characteristics, EQ-5D dimension scores and values, EQ VAS scores, EORTC QLQ-C30 scale/item and summary scores, and FACT-BMT subscale and total scores. RESULTS The mean EQ-5D value was 0.36. In total, 96% of the patients reported problems with usual activities, 92% with pain/discomfort, 84% with mobility, 80% with self-care, and 72% with anxiety/depression. The mean EORTC QLQ-C30 summary score was 43.50. Mean scale/item scores ranged from 21.79 to 60.00 for functioning scales, from 39.74 to 75.21 for symptom scales, and from 5.33 to 91.67 for single items. The mean FACT-BMT total score was 75.31. Mean subscale scores ranged from 10.09 for physical well-being to 23.94 for social/family well-being. CONCLUSION Our study showed that HRQoL in patients with SR-aGvHD is poor. Improving HRQoL and symptom management in these patients should be a top priority.
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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
Zhao, K., Lin, R., Fan, Z., Chen, X., Wang, Y., Huang, F., Xu, N., Zhang, X., Zhang, X., Xuan, L., et al
Journal of hematology & oncology. 2022;15(1):22
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Editor's Choice
Abstract
BACKGROUND Steroid-resistant (SR) acute graft-versus-host disease (aGVHD) lacks standard second-line treatment. Mesenchymal stromal cells (MSCs) have potential efficacy in SR aGVHD. We aimed to assess the efficacy and safety of MSCs combined with basiliximab and calcineurin inhibitor as second-line therapy for SR aGVHD. METHODS A randomized phase 3 trial involved 203 SR aGVHD patients at nine centers in China (September 2014-March 2019). Participants were randomized at a 1:1 ratio to receive second-line therapy with (n = 101) or without (n = 102) MSCs. The primary endpoint was the overall response (OR) at day 28. Secondary and safety endpoints included durable OR at day 56, failure-free survival, overall survival (OS), chronic GVHD (cGVHD), infection, hematological toxicity and relapse. RESULTS Of 203 patients, 198 (97.5%; mean age, 30.1 years; 40.4% women) completed the study. The OR at day 28 was higher in the MSC group than the control group (82.8% [82 patients] vs. 70.7% [70]; odds ratio, 2.00; 95% confidence interval [CI], 1.01-3.94; P = 0.043). The durable OR at day 56 was also higher in the MSC group (78.8% [78 patients] vs. 64.6% [64]; odds ratio, 2.02; 95% CI, 1.08-3.83; P = 0.027). The median failure-free survival was longer in the MSC group compared with control (11.3 months vs. 6.0 months; hazard ratio (HR) 0.68; 95% CI, 0.48-0.95, P = 0.024). The 2-year cumulative incidence of cGVHD was 39.5% (95% CI, 29.3-49.4%) and 62.7% (51.4-72.1%) in the MSC and control groups (HR 0.55, 95% CI, 0.36-0.84; P = 0.005). Within 180 days after study treatments, the most common grade 3 and 4 adverse events were infections (65 [65.7%] in the MSC group vs. 78 [78.8%] in the control group) and hematological toxicity (37 [37.4%] vs. 53 [53.5%]). The 3-year cumulative incidence of tumor relapse was 10.1% (95% CI, 5.2-17.1) and 13.5% (7.5-21.2%) in the MSC and control groups, respectively (HR 0.75, 95% CI, 0.34-1.67, P = 0.610). CONCLUSIONS MSCs plus second-line treatments increase the efficacy of SR aGVHD, decrease drug toxicity of second-line drugs and cGVHD without increasing relapse, and are well-tolerated. MSCs could be recommended as a second-line treatment option for aGVHD patients. Trial registration clinicaltrials.gov identifier: NCT02241018. Registration date: September 16, 2014, https://clinicaltrials.gov/ct2/show/NCT02241018 .
PICO Summary
Population
Patients with steroid resistant (SR) acute graft-versus-host-disease in 9 centres in China (n=203)
Intervention
Second-line GvHD therapy with mesenchymal stromal cells (n=101)
Comparison
Second-line GvHD therapy without mesenchymal stromal cells (n=102)
Outcome
Of 203 patients, 198 (97.5%; mean age, 30.1 years; 40.4% women) completed the study. The OR at day 28 was higher in the MSC group than the control group (82.8% [82 patients] vs. 70.7% [70]; odds ratio, 2.00; 95% confidence interval [CI], 1.01-3.94). The durable OR at day 56 was also higher in the MSC group (78.8% [78 patients] vs. 64.6% [64]; odds ratio, 2.02; 95% CI, 1.08-3.83). The median failure-free survival was longer in the MSC group compared with control (11.3 months vs. 6.0 months; hazard ratio (HR) 0.68; 95% CI, 0.48-0.95). The 2-year cumulative incidence of cGVHD was 39.5% (95% CI, 29.3-49.4%) and 62.7% (51.4-72.1%) in the MSC and control groups (HR 0.55, 95% CI, 0.36-0.84). Within 180 days after study treatments, the most common grade 3 and 4 adverse events were infections (65 [65.7%] in the MSC group vs. 78 [78.8%] in the control group) and hematological toxicity (37 [37.4%] vs. 53 [53.5%]). The 3-year cumulative incidence of tumor relapse was 10.1% (95% CI, 5.2-17.1) and 13.5% (7.5-21.2%) in the MSC and control groups, respectively (HR 0.75, 95% CI, 0.34-1.67).
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A Phase 3 randomized study of Remestemcel-L versus placebo added to second line therapy in patients with steroid refractory acute graft versus host disease
Kebriaei, P., Hayes, J., Daly, A., Uberti, J., Marks, D. I., Soiffer, R., Waller, E. K., Burke, E., Skerrett, D., Shpall, E., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
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Editor's Choice
Abstract
BACKGROUND Uncontrolled studies have suggested that bone marrow-derived mesenchymal stem cells (MSC) may be effective against acute graft-versus-host disease (aGvHD). We conducted a multicenter, randomized study to assess the efficacy of using ex vivo cultured adult human MSC (remestemcel-L) in addition to second-line therapy to treat steroid refractory aGvHD (NCT00366145). METHODS Two-hundred sixty patients, 6 months to 70 years of age, were enrolled from August 2006 to May 2009, and were randomized 2:1 to receive 8 intravenous infusions of remestemcel-L or placebo, given over 4 weeks, in addition to second-line therapy according to institutional standards. Four additional infusions over 4 weeks were indicated for patients with incomplete response at Day 28. Randomization was stratified by aGVHD grade. Efficacy and safety were assessed through 180 days of follow-up, with the primary endpoint being durable complete response (DCR), defined as complete resolution of aGvHD symptoms for any period of at least 28 days after beginning treatment. FINDINGS Remestemcel-L did not meet the primary endpoint of greater DCR in the intent-to-treat population (35% vs. 30%; p=0.42). In post-hoc analyses patients with liver involvement who received at least one infusion of remestemcel-L had a higher DCR, and higher overall complete or partial response rate (OR) than those who received placebo (29% vs. 5%; p=0.047). Furthermore, pediatric patients had a higher OR with MSC compared with placebo (64% vs. 23%; p=0.05). Similar rates of adverse events were observed between treatment groups. INTERPRETATION Remestemcel-L was safe and well-tolerated. Results of this study did not demonstrate superior DCR compared to placebo when added to standard of care. The favorable clinical responses seen in some patient subsets may warrant further investigation.
PICO Summary
Population
Patients with steroid-refractory GvHD (n=260)
Intervention
Ex vivo cultured adult human mesenchymal stromal cells (remestemcel-L), alongside second-line therapy (n=173)
Comparison
Placebo, alongside second-line therapy (n=87)
Outcome
Remestemcel-L did not meet the primary endpoint of greater durable complete response (DCR) in the intent-to-treat population (35% vs. 30%). In post-hoc analyses patients with liver involvement who received at least one infusion of remestemcel-L had a higher DCR, and higher overall complete or partial response rate (OR) than those who received placebo (29% vs. 5%). Furthermore, pediatric patients had a higher OR with MSC compared with placebo (64% vs. 23%). Similar rates of adverse events were observed between treatment groups.