The 2nd China Blood and Transplant Forum Announces Significantly | Basiliximab has a significant effect in the treatment of SR-aGVHD

Acute graft versus host disease (aGVHD) is a unique and common complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), which seriously affects the prognosis of the recipient [1]
.

At present, the first-line standard treatment for aGVHD is glucocorticoid, but the effective rate is only about 50%.
When hormone therapy fails, it is steroid refractory (SR) [1-4]
.

The choice of treatment for SR-aGVHD patients directly affects the prognosis, but the best treatment plan is currently inconclusive [2,5]
.

 Interleukin-2 receptor antagonists (IL-2R antagonists, IL-2RA) basiliximab is the most used SR-aGVHD therapeutic drug in China so far, but there is not enough data to compare the various treatment options horizontally.
Efficacy [2]
.

Recently, a meta-analysis of 4 IL-2RA treatments for SR-aGVHD by Professor Huang Xiaojun’s team from Peking University People’s Hospital-Director Mo Xiaodong was published on Frontiers inImmunology, and at the Academic Annual Meeting of the Hematology Branch of the China Association for the Promotion of International Health Care Cum public report on the second China Blood and Transplant Forum, here is an in-depth interpretation of the content of the article, in order to provide a reference for the treatment of SR-aGVHD [6]
.

Literature review and meta-analysis by searching important medical databases.
Existing studies have shown that basiliximab, daclizumab, enrolizumab, and dini-interleukin 2 four types of IL-2RA are safe in patients with SR-aGVHD Effective, but due to the heterogeneity of the research design, the results vary widely [6]
.

So far, there has been no study comparing the efficacy of 4 IL-2RA [6]
.

To this end, Professor Xiaojun Huang's team-Director Mo Xiaodong conducted this meta-analysis to evaluate the efficacy and safety of four IL-2RA-based treatments in patients with SR-aGVHD through a meta-analysis of published literature
.

A total of 31 studies were included in the analysis, and the research flow chart is as follows [6]
.

Figure 1 Study flow chart The highest overall response rate (ORR) of basiliximab treatment showed that the ORR of basiliximab treatment for SR-aGVHD was 0.
81 (95% CI: 0.
74–0.
87), which was better than Clemizumab's 0.
71 (95% CI: 0.
56–0.
82) is also better than enrolizumab and denil-interleukin 2 (Figure 2) [6]
.

The analyses of prospective studies and retrospective studies have consistently shown that the ORR of basiliximab is the best [6]
.

Figure 2 ORR at any time after treatment (overall) The results of ORR analysis at 1 month after treatment are consistent with the overall results, and the ORR at 1 month after basiliximab treatment is the best (Figure 3) [6]
.

Figure 3 ORR 1 month after treatment In summary, basiliximab-based treatment showed the highest ORR (up to 0.
81) at any time point or within 1 month of treatment [6]
.

The best complete response rate (CRR) of basiliximab treatment is 0.
55 (95% CI : 0.
42-0.
68), 0.
42 (95% CI: 0.
29-0.
56), 0.
30 (95% CI: 0.
16–0.
51) and 0.
37 (95% CI: 0.
24–0.
52), of which basiliximab has the highest CRR (Figure 4) [6]
.

Figure 4 CRR at any time after treatment After 1 month of treatment and in the analysis of prospective and retrospective studies respectively, the CRR of basiliximab was the highest, up to 0.
64 [6]
.

Basiliximab showed a high response rate in different involved organs.
Comparative analysis of the reaction rates of different involved organs (skin, gastrointestinal tract and liver) after 4 IL-2RA treatments.
Basiliximab treatments were all Shows higher ORR and CRR, and basiliximab treatment of gastrointestinal and liver SR-aGVHD CRR was significantly better than daclizumab group (p value is 0.
012 and <0.
001, respectively) [6]
.

Figure 5 The response rate of IL-2RA to SR-aGVHD in different affected organs.
The total infection rate after basiliximab treatment is low.
Analysis of the incidence of infection after treatment with 4 IL-2R antagonists, the results show that basiliximab The total infection rate is equivalent to that of daclizumab, which is significantly lower than that of enrolizumab [6]
.

Figure 6 The incidence of infection after four IL-2RA treatments.
The incidence of cGVHD after basiliximab treatment is relatively low.
Analysis of the incidence of chronic graft-versus-host disease (cGVHD) after four IL-2RA treatments shows the results , The incidence of cGVHD after basiliximab, daclizumab, enolumomab and dini-interleukin 2 treatment was 52.
5% (95% CI: 37.
5%–67.
5%), 64.
3% (95%) CI: 41.
3%-87.
2%), 70.
8% (95% CI: 24.
0%-100.
0%) and 60.
0%.
Among them, the incidence of cGVHD after basiliximab treatment is relatively low [6]
.

The overall survival rate (OS) of basiliximab treatment is high.
The analysis shows that the OS of basiliximab and daclizumab are equivalent, 53.
6% (95% CI: 29.
9%–77.
31%) and 56.
5%, respectively (Included in only two studies, range: 40%-72.
9%), which was higher than 36.
2% (95% CI: 18.
6%-53.
8%) in the enolomab group
.

Only two studies were included in the indaclizumab group, and the results need to be interpreted with caution
.

Figure 7 Survival after IL-2RA treatment Conclusion: Basiliximab has a significant therapeutic effect on SR-aGVHD.
In summary, among the four types of IL-2RA, basiliximab treatment can obtain the highest ORR and CRR.
It showed higher ORR and CRR in different organs involved, and the total infection rate was significantly lower than enrolimab-based treatment
.

In short, basiliximab has a significant effect on the treatment of SR-aGVHD
.

Conclusion Basiliximab is the most commonly used drug for the treatment of SR-aGVHD in China so far.
It is also the "NCCN Clinical Practice Guidelines: Hematopoietic Cell Transplantation" and "Chinese Society of Clinical Oncology (CSCO) Allogeneic Hematopoietic Stem Cell Transplantation for Leukemia and Myelodysplastic Abnormalities" Syndrome Guidelines (2021 Edition)", "Chinese Expert Consensus on Allogeneic Hematopoietic Stem Cell Transplantation for Treatment of Hematological Diseases (III)-Acute Graft Versus Host Disease (2020 Edition)" and other guidelines consensus recommend the only IL for the treatment of SR-aGvHD -2RA drugs [2,5,7]
.

The total effective rate in adult SR-aGVHD is 78.
7%-86.
8%, and the CR rate is 60.
9%-69.
8%; the total effective rate of SR-aGVHD after hematopoietic stem cell transplantation in children is 85%, and the CR rate is 85%.
Up to 74%[2]
.

 Comparing the 4 types of IL-2RA, basiliximab treatment showed that: ①There are higher response rates in different involved organs, especially in the intestine and liver SR-aGVHD; ②The total infection rate and the incidence of cGVHD are both Lower; ③A higher OS can be obtained[6]
.

On the whole, basiliximab has a significant effect on the treatment of SR-aGVHD, and it is hoped to improve the prognosis of patients with SR-aGVHD
.

This study is the first meta-analysis to compare the efficacy and safety of different IL-2RAs, and further proves the significant efficacy and safety of basiliximab in the treatment of SR-aGVHD, which is of great significance in the treatment of SR-aGVHD
.

Professor Xiaodong Mo, Doctor of Hematology, Department of Hematology, Peking University People’s Hospital, Associate Chief Physician, Associate Professor, Master's Supervisor.
Research direction: Clinical and translational research related to the prevention and treatment of recurrence after allogeneic hematopoietic stem cell transplantation for acute leukemia.
The first/corresponding author published an SCI paper 41 Beijing “Top-notch Young Talents” Beijing “High-level Innovative and Entrepreneurial Talents” hosted/participated in national, provincial and ministerial projects such as the National Natural Science Foundation of China and the Capital Health Development Scientific Research Project won the second prize of the National Science and Technology Progress Award (10 /10), the first prize of the Chinese Medical Science and Technology Award (10/15), the first prize of the Ministry of Education's Science and Technology Progress Award (10/15), the first prize of the China Medical Science and Technology Award (15/15), one Chinese elderly blood each Member of the Comprehensive Evaluation Committee Shen Mengzhu, Correspondence Editor of Chinese Journal of Metastatic Tumor The author published 1 SCI paper and 1 poster and won the 2021 Peking University People’s Hospital Excellence Award.
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Meta-Analysis of Interleukin-2 Receptor Anta-gonists as the Treatment for Steroid-Refractory Acute Graft-Versus-Host Disease[J].
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2021, 12, 749266.
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2021, 12, 749266.
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September 30, 2021.
Stamp "Read the original", we will make progress togetherZhang XH, et al.
Meta-Analysis of Interleukin-2 Receptor Anta-gonists as the Treatment for Steroid-Refractory Acute Graft-Versus-Host Disease[J].
Fron-tiers in Immunology.
2021, 12, 749266.
[7] NCCN Clinical Practice Guidelines in Oncology:Hematopoietic Cell Transplantation (HCT): Pre-Transplant RecipientEvaluation and Management of Graft-Versus-Host Disease, Version 5.
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Stamp "Read the original text", we make progress togetherZhang XH, et al.
Meta-Analysis of Interleukin-2 Receptor Anta-gonists as the Treatment for Steroid-Refractory Acute Graft-Versus-Host Disease[J].
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September 30, 2021.
Stamp "Read the original text", we make progress together