Registry Analysis Finds Off-Label Rituximab Improves Outcomes in Patients With iTTP

For patients with de novo immune thrombocytopenic purpura (iTTP), adding rituximab to corticosteroids appears to delay, but not prevent, relapse, according to results from a registry analysis presented at the 2019 ASH Annual Meeting. In subgroup analyses, the authors also found that Caucasian patients with relapsed iTTP had significantly longer relapse-free survival (RFS), compared with African American patients.

“When rituximab was added to corticosteroids, 5-year RFS for Caucasian patients with relapsed disease improved dramatically,” said lead investigator Marshall Mazepa, MD, from the University of Minnesota, during his presentation.

Standard treatments for iTTP include therapeutic plasma exchange and corticosteroids, and rituximab is often used to treat de novo and relapsed/refractory iTTP, Dr. Mazepa explained. However, there are no large randomized trials on which to base its use. To determine the effects of adding off-label rituximab to standard treatment, the authors reviewed data from the U.S. Thrombotic Microangiopathy Consortium iTTP registry. First, the authors assessed the effect of rituximab added to corticosteroids and therapeutic plasma exchange in de novo iTTP patients, then separately evaluated the treatment effect in relapse.

As of July 2019, the registry contained 775 patients who were diagnosed with iTTP (defined as ADAMTS13 <10%, or <20% with an inhibitor or antibody detected at any point). Patients experienced a total of 1,397 unique iTTP episodes.

The analysis included 375 evaluable patients with de novo disease; most of these patients were treated with corticosteroids alone (n=188), followed by corticosteroids plus rituximab (n=131), or other therapies (n=56). In the corticosteroids plus rituximab group, rates of 1-year and 3-year RFS were significantly higher compared with patients who received corticosteroids alone: 0.93 vs. 0.78 (p=0.0002) and 0.82 vs. 0.66 (p=0.004), respectively. However, there was no difference at five years (0.60 for corticosteroids plus rituximab vs. 0.56 for corticosteroids alone; p=0.39).

The researchers reported that the risk of relapse (defined as a recurrence of iTTP ≥30 days of remission) decreased with later treatment year (hazard ratio [HR] = 0.95; p=0.03), “consistent with rituximab use increasing over time.” African American patients also had a higher risk of relapse, compared with Caucasian patients (HR=1.83; p=0.02). In both African Americans and Caucasians, rituximab appeared to delay relapse for some patients by about 3 years.

Next, the authors examined outcomes in 426 patients who experienced a total of 743 episodes of relapsed iTTP, finding a significant interaction between treatment and race (p=0.0007).

Among Caucasian patients, the addition of rituximab significantly improved RFS, compared with corticosteroids alone (HR=0.15; p<0.0001); however, there was no significant difference in African American patients (HR=1.15; p=0.43). Estimated 5-year RFS was about 50% and 40% in African American patients with de novo iTTP and relapsed iTTP, respectively, regardless of treatment with rituximab. For Caucasian patients with de novo iTTP, though, 5-year RFS was approximately 80%. The most drastic improvement in RFS was found in Caucasian patients with relapsed iTTP at five years, Dr. Mazepa noted, which improved from 40% to 80% with the addition of rituximab.

“Further investigation is warranted to determine the mechanisms of this difference in the response to rituximab in relapsed iTTP to improve outcomes in African Americans,” Dr. Mazepa said. “There is a critical need for trials of alternative immunosuppression in patients who experience early relapse after treatment with rituximab.”

The findings from this registry analysis are limited by the potential for missing or incomplete information.

The authors report no relevant conflicts of interest.


Mazepa MA, Evans M, Davis E, et al. Differential effect of rituximab on relapse-free survival in de novo and relapsed immune thrombotic thrombocytopenic purpura in African-American and Caucasian populations. Abstract #90. Presented at the 2019 ASH Annual Meeting, December 7, 2019; Orlando, FL.