Blood Peking University Zhang Xiaohui's team discovers a potential new treatment for immune thrombocytopenia

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iNature Immune Thrombocytopenia (ITP) is an autoimmune disease characterized by increased platelet destruction and insufficient platelet production
.

Corticosteroids and intravenous immunoglobulin (IVIg) are first-line treatments
.

About one-third of ITP patients fail to recover; in addition, most patients who respond to first-line treatment will relapse and require further second-line treatment
.

However, the best second-line treatment is still uncertain
.

This study aims to compare all-trans retinoic acid (ATRA) plus low-dose rituximab (LD-RTX) and LD-RTX monotherapy in patients with corticosteroid resistance or recurrent immune thrombocytopenia (ITP) The efficacy and safety
.

On October 19, 2021, Peking University Zhang Xiaohui’s team published a research paper entitled "All-trans retinoic acid plus low-dose rituximab vs low-dose rituximab in corticosteroid-resistant or relapsed ITP" online at Blood (IF=22.
11).
The patients enrolled in the study were randomly divided into 2 groups at a 2:1 ratio: 112 patients received LD-RTX plus ATRA, and 56 patients received LD-RTX monotherapy
.

Overall response (OR), defined as confirming a platelet count ≥ 30 × 109/L on at least two different occasions (at least 7 days apart), and increasing at least the baseline platelet count without any other ITP-specific treatment Doubled
.

The OR of the LD-RTX plus ATRA group (80%) was more than that of the LD-RTX monotherapy group (59%), and there was no bleeding within 1 year after enrollment (between groups difference, 0.
22; 95% CI, 0.
07 To 0.
36)
.

Sustained response (SR) was defined as maintaining a platelet count of> 30 x 109/L, no bleeding, and achieving OR within 1 year after enrollment and not requiring any other ITP-specific treatment for 6 consecutive months.
68 patients in the combined treatment group ( 61%) patients and 23 (41%) patients in the monotherapy group achieved this goal (between-group difference, 0.
20; 95% CI, 0.
04 to 0.
35)
.

The 2 most common AEs in the combination group were dry skin and headache or dizziness
.

In summary, the results of this study indicate that ATRA plus LD-RTX significantly increases the overall and sustained response, indicating that ITP in adults who are resistant to corticosteroids or relapse is a promising treatment option
.

Primary immune thrombocytopenia (ITP) is an autoimmune disease characterized by increased platelet destruction and insufficient platelet production
.

Corticosteroids and intravenous immunoglobulin (IVIg) are first-line treatments
.

About one-third of ITP patients fail to recover; in addition, most patients who respond to first-line treatment will relapse and require further second-line treatment
.

However, the best second-line treatment is still uncertain
.

Rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, can exert its therapeutic effect through the rapid consumption of CD20-positive B lymphocytes and the regulation of T cells.
It has been frequently used in ITP treatment
.

There is currently no gold standard solution for RTX
.

A schedule has been proposed, including standard dose (SD) (375 mg/m2 4 times a week) and low dose (LD) (100 mg flat dose 4 times a week)
.

Previous studies using SD-RTX have shown that the overall response (OR) is close to 60%, and the sustained response (SR) is 30-40%
.

A meta-analysis of LD-RTX in ITP showed a comparable OR.
Compared with SD-RTX, LD-RTX usually means a significant reduction in expenditure ($10,000-40 000 per 4 infusion courses) and easier Management
.

These advantages indicate that LD-RTX may be a promising treatment option for ITP
.

However, it is reported that the median response time (TTR) of LD-RTX monotherapy is 30 days, which is significantly longer than SD-RTX (10.
5 days)
.

Compared with SD-RTX, LD-RTX has a lower SR
.

In addition, another study reported that for patients with corticosteroid resistance or relapsed ITP, no difference in OR and treatment failure rate between SD-RTX and placebo was observed within 78 weeks of treatment, indicating that the general recommendation does not support the SD-RTX monotherapy for corticosteroid-resistant or recurrent ITP
.

According to the pharmacokinetic data of RTX, increasing doses of RTX may maintain the concentration and prolong the clearance time of B cells
.

Additional doses of RTX have been shown to improve the efficacy of rheumatoid arthritis and lymphoma treatment
.

All-trans retinoic acid (ATRA) is a key metabolite of vitamin A and is involved in cell proliferation and differentiation
.

ATRA has the effect of inducing megakaryocyte (MK) differentiation.
A multi-center randomized trial was previously conducted.
Compared with danazol monotherapy (200 mg twice a day), it proved that ATRA (10 mg twice a day) and up to The combination of nazole (200 mg twice a day) achieved an improvement in overall response (82% vs.
44%; odds ratio [OR] 5.
95, 95% CI 2.
29-15.
43) and a 12-month remission (62% vs.
25%; OR 4.
94, 95% CI 2.
03-12.
02)
.

Since RTX and ATRA have different mechanisms in the treatment of ITP, the combination of LD-RTX (additional 2 doses) and ATRA may work together based on the "double-click" mechanism for platelet production and destruction, which may overcome long TTR and increase LD -SR rate of RTX
.

Therefore, this study aims to determine the efficacy and safety of ATRA plus LD-RTX compared with LD-RTX monotherapy in patients with corticosteroid resistance or relapsed ITP
.

The patients enrolled in the study were randomly divided into 2 groups at a 2:1 ratio: 112 patients received LD-RTX plus ATRA, and 56 patients received LD-RTX monotherapy
.

Overall response (OR), defined as confirming a platelet count ≥ 30 × 109/L on at least two different occasions (at least 7 days apart), and increasing at least the baseline platelet count without any other ITP-specific treatment Doubled
.

The OR of the LD-RTX plus ATRA group (80%) was more than that of the LD-RTX monotherapy group (59%), and there was no bleeding within 1 year after enrollment (between groups difference, 0.
22; 95% CI, 0.
07 To 0.
36)
.

Sustained response (SR) was defined as maintaining a platelet count of> 30 x 109/L, no bleeding, and achieving OR within 1 year after enrollment and not requiring any other ITP-specific treatment for 6 consecutive months.
68 patients in the combined treatment group ( 61%) patients and 23 (41%) patients in the monotherapy group achieved this goal (between-group difference, 0.
20; 95% CI, 0.
04 to 0.
35)
.

The two most common AEs in the combination group were dry skin and headache or dizziness
.

In summary, the results of this study indicate that ATRA plus LD-RTX significantly increases the overall and sustained response, indicating that ITP in adults who are resistant to corticosteroids or relapse is a promising treatment option
.

Reference message: https://ashpublications.
org/blood/article-abstract/doi/10.
1182/blood.
2021013393/477386/All-trans-retinoic-acid-plus-low-dose-rituximab-vs?redirectedFrom=fulltext