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Patient Race Linked to Relapse Risk and Rituximab Response in iTTP

September 26, 2022

October 2022

Tess Stafford

Tess Stafford is the editorial assistant of ASH Clinical News.

Race affects overall relapse risk and response to rituximab in immune-mediated thrombotic thrombocytopenic purpura (iTTP), according to a study published in Blood. The study showed that Black patients with iTTP may require earlier retreatment, closer monitoring, or alternative immunotherapy.

These results suggest that treatment needs to be individualized for patients in remission from iTTP, explained lead author Shruti Chaturvedi, MBBS, of Johns Hopkins University in Baltimore, Maryland.

iTTP is a chronic relapsing disorder that is caused by a deficiency of ADAMTS13, a von Willebrand factor-cleaving protease. iTTP mortality rates have dramatically improved from greater than 90% to less than 10%, but the condition carries mortality risks with each episode.

Racial disparities in treatment outcomes have not been thoroughly explored despite Black patients making up the majority of iTTP cohorts. To analyze iTTP survival and relapse in relation to race, researchers conducted a multicenter study using data from the U.S. Thrombotic Microangiopathy (USTMA) Consortium iTTP Registry.

Dr. Chaturvedi and colleagues evaluated 645 patients diagnosed with iTTP from 15 USTMA sites who were treated between 1995 and 2020. Treatment groups included corticosteroids only and corticosteroids plus rituximab (four doses of 375 mg/m2). Primary outcomes included acute iTTP-associated death and relapse-free survival (RFS).

Results indicated that race, time to ADAMTS13 recovery, and prior relapse were relapse risk factors. As a result, patients were grouped by episode, race, and treatment. Patients were classified as relapsed or de novo (first episode).

Of 1,049 iTTP episodes, 3.3% resulted in acute iTTP-associated death. Results did not demonstrate a statistically significant difference in mortality based on race (3.2% of Black patients, 3.7% of white patients, and 2.3% of other/unknown). However, results associated age, male sex, and de novo episode with an increased risk of mortality.

Further results showed 34% of patients experienced relapse, and Black patients had shorter RFS (hazard ratio [HR] = 1.60, 95% CI 1.16-2.21). After examining race and treatment further, Dr. Chaturvedi and colleagues found that treatment with corticosteroids plus rituximab improved RFS in white patients (HR=0.37, 95% CI 0.18-0.73) but not in Black patients (HR=0.96, 95% CI 0.71-1.31).

When analyzed in subcohorts of relapse status and race by treatment (de novo and white, de novo and Black, relapsed and white, and relapsed and Black), treatment with rituximab did not improve RFS in white or Black patients with de novo iTTP but did delay relapse. However, treatment with rituximab had a statistically significant effect on improving RFS in white patients with relapsed iTTP but not in Black patients with relapsed iTTP.

In comparing the groups, a statistically significant effect was observed only for white patients (see TABLE).

“When we found that Black patients had a higher rate of relapse, we thought this might be due to issues around access to care – perhaps rituximab was offered at lower rates to certain groups,” Dr. Chaturvedi said. “However, this was not the case. The proportion of episodes treated with rituximab were similar in Black and white participants (51% vs. 47%). The causes of underlying differences in relapse rate are unknown but may be related to other biologic and environmental factors.”

Limitations of the study included non-randomized rituximab therapy, loss of follow-up, and lacking ADAMTS13 long-term data and biological samples. Additionally, mortality rates may have been underestimated for the cohort, as patients with fatal episodes occurring before 2006 were excluded.

“We hope that these findings will improve care for patients with iTTP,” Dr. Chaturvedi said. “Black patients, in particular, are likely to have a much shorter-lived response to rituximab and benefit from closer monitoring and alternative immunosuppressive therapies.”

Any conflicts of interest declared by the authors can be found in the original article.

Reference

Chaturvedi S, Antun AG, Farland A, et al. Race, rituximab, and relapse in TTP [published online ahead of print, 2022 July 7]. Blood. doi: 10.1182/blood.2022016640.

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