Predictors of Response to Rituximab in Chronic Immune Thrombocytopenia: Do Race, Gender and ABO Blood Type Matter?
Authors: Laharwal Mehak M , Sweeney Ryan , Samhouri Yazan , Shah Deep 
Published: December 2023

Introduction:
Immune thrombocytopenia (ITP)is characterized by immune mediated destruction of platelets causing isolated thrombocytopenia with a peripheral blood platelet count &lt;100,000/microL in the absence of other causes that may be associated with thrombocytopenia. It remains a diagnosis of exclusion. Corticosteroids are the first-line treatment for ITP and more than 75% of adults with ITP will respond to them. However, approximately 70-80% of adult patients with ITP will experience treatment failure with corticosteroids or become dependent on them and require second-line therapy. Various options in the second line setting include thrombopoietin receptor agonists, rituximab, and splenectomy.
In one study rituximab was noted to result in an overall platelet count response in 62.5% of adults. However not all patients remain in remission and clinical factors that are predictive of response are lacking. Racial disparities are known to predict response to rituximab in other hematologic disorders such as immune mediated thrombotic thrombocytopenic purpura (Mezapa et al, 2022). Herein, we are examining the effect of race, gender and ABO blood type on response to rituximab in patients diagnosed with ITP.
Methods:
This retrospective cohort study included adult patients, aged 18 and above, with a diagnosis of ITP who had received single agent rituximab within a multihospital academic healthcare system between January 2015 and December 2022. Initially 196 patients were identified but only 127 of those were included in the study. We excluded patients with missing response data, and those with combined rituximab and other therapies (stable or decreasing doses of steroids were allowed).
Our primary end point was any response to rituximab by day 180 after starting rituximab. Any response was defined as complete response or partial response. Complete response was defined as platelet count ≥ 100,000 /microL and absence of bleeding. Partial response was defined as platelet count of at least 30,000/microL after week 4 from rituximab administration or doubling of platelet count from baseline without administration of any platelet increasing therapy. Our secondary end point was relapse rate which was defined as platelet count below 100,000/microL if complete response had been attained or below 30,000/microL or less than 2 fold increase of baseline platelet count. We also investigated clinical and socioeconomic predictors of response.
Exploratory analysis was performed. Summary statistics are presented as percentages for categorical data and median with interquartile range for quantitative data. Chi square test was used to compare percentages and t-test was used to compare means. Univariate and multivariate regression models were used to analyze the predictors of any response to rituximab. Kaplan-Meier method was used to calculate estimates of relapse-free survival, and log-rank test was used to compare these estimates.
Result:
We identified 127 patients diagnosed with ITP who received rituximab. The median age was 64 years (IQR 48-74), there were 46.5% females. The majority of the patients were Caucasians (95.3%), and rituximab was most commonly received as a second line therapy (73.2%). Median initial platelet count was 28,000/microL. Complete response was observed in 50% of African American patients compared with 43.0% in Caucasian patients (p-value 0.63). No predictors for any response on univariate or multivariate analyses were found. Race (OR 0.30, 95CI 0.03-3.25, p-value 0.32) and female gender (OR 0.76, 95CI 0.33-1.76, p-value 0.51) did not affect response to rituximab in our patient cohort. Relapse rate was 60% in African American patients versus 67.5% in Caucasians (p-value 0.72), and 68.7% in males versus 64.9% in females (p-value 0.71). ABO blood type also did not predict a response to Rituximab in our patient population (Table 1)
Conclusion:
In our study, race and gender did not affect response or relapse rates after rituximab treatment in chronic ITP. Patient's ABO blood type also did not predict a difference in response to Rituximab. However, our study was limited by a small sample size and further multi-institutional analysis is warranted to confirm the findings of our study.