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Relapse-Free Survival Progressively Shortens in Black Patients With Rituximab-Treated iTTP

January 30, 2025

February 2025

Katie Robinson

Katie Robinson is a medical writer based in New York.

In patients with relapsing immune thrombotic thrombocytopenic purpura (iTTP), successive rituximab treatment shortens relapse-free survival (RFS), a finding most pronounced in Black patients, who comprise most of the individuals in the U.S. with this chronically relapsing disorder. These findings were published in Blood Advances.

“We identified that there is a subgroup of mostly (self-identified) Black patients with iTTP who have shorter and shorter time to relapse with successive episodes (each treated with rituximab, which is standard of care),” corresponding author Shruti Chaturvedi, MBBS, MS, of Johns Hopkins University in Baltimore, said.

“This does not mean we should not use rituximab for our Black patients with iTTP. Rituximab is generally well tolerated and is the immunomodulator with most evidence of benefit in iTTP,” Dr. Chaturvedi said.However, our results indicate that patients with relapsing iTTP require close monitoring and earlier consideration of alternative regimens if the response to rituximab is suboptimal.”

The goal of rituximab treatment is to prevent relapse in patients with iTTP, a rare life-threatening disorder caused by autoantibody-mediated ADAMTS13 deficiency. However, it is unknown whether the response to rituximab is as durable with subsequent treatment courses administered for disease relapse.

In the study, the researchers used data from 310 multiply relapsing patients (median age at time of episode = 45 years, 68% female) with a total of 384 rituximab-treated episodes, recorded in the U.S. Thrombotic Microangiopathy Consortium (USTMA) retrospective iTTP registry, which includes adults treated between 1995 and 2020 at 15 high-volume academic centers. The researchers evaluated clinical RFS with subsequent courses of rituximab treatment. They also evaluated overall RFS — a composite of time to clinical relapse, ADAMTS13 relapse, or preemptive rituximab — in a prospective cohort of 97 patients (median age at time of episode = 45 years, 73% female) with a total of 188 rituximab-treated episodes, from Johns Hopkins University and the University of Minnesota.

In the USTMA registry, a shorter median clinical RFS occurred after the second or later rituximab courses compared with the first, at 2.1 and 6.0 years, respectively (p=0.04). In Black patients, clinical relapse risk after the second and later rituximab courses stood significantly higher compared with the first (hazard ratio [HR] = 2.82; 95% CI 1.52-5.24; p=0.001). In white patients, the researchers found no significant difference in the risk (HR=1.86; 95% CI 0.22-15.80; p=0.57).

In the prospective cohort, overall RFS progressively shortened after each rituximab-treated episode. For the first, second, and subsequent treated episodes, the respective median RFS stood at 2.8 years (IQR 2.0-6.0), 2.0 years (IQR 1.2-3.6), and 1.0 year (IQR, 0.5-2.5, p=0.0001). Similar to clinical RFS, this finding was “driven predominantly by a loss of response durability with later courses in Black patients,” the authors wrote. For Black and white patients, the median overall RFS in the first episode was 2.7 years versus 3.6 years, respectively. This decreased to 0.9 years in Black patients on third and subsequent rituximab-treated episodes and to 1.5 years in white patients.

“For clinicians, the important clinical takeaways are that patients with multiple iTTP relapses should be monitored closely — we suggest every three months,” Dr. Chaturvedi said.Rituximab is still first-line immunosuppression, but if there is little improvement in ADAMTS13 levels or if levels drop back down less than a year later, one should consider alternative immunosuppression strategies.

“There are no large studies to guide the choice of therapy after rituximab (weekly for four to six weeks), but alternatives that can be used are maintenance rituximab (a single dose every three to six months similar to follicular lymphoma regimens) or drugs such as cyclosporine. More recently, there are promising data on daratumumab as a salvage strategy in iTTP,” Dr. Chaturvedi added.

Limitations to the study included the inadequate available data on later treatment courses due to loss to follow-up, with smaller patient groups receiving third and later courses. Additionally, because the USTMA registry did not include serial ADAMTS13 monitoring data, the researchers evaluated ADAMTS13 relapse and preemptive rituximab therapy in smaller prospective cohorts.

“We hope that our study will lend momentum to the quest to develop personalized immunosuppressive strategies in iTTP,” Dr. Chaturvedi concluded.

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

Reference

Fatola A, Evans M, Brown J, et al. Relapse free survival progressively shortens in a subset of Black patients with immune TTP treated in the rituximab era [published online ahead of print, 2024 Dec. 3]. Blood Adv. doi: 10.1182/bloodadvances.2024013313.

 

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