For patients with thrombotic thrombocytopenic purpura (TTP), treatment with rituximab prevented relapse in the first year after administration, but the protective effect waned over time, according to results from a study presented at the 2018 ASH Annual Meeting. The authors, led by Lova Sun, MD, from Massachusetts General Hospital, also found that younger age, prior episodes of TTP at presentation, and a non-O blood type predicted a higher risk of relapse.
“Rituximab has been increasingly incorporated into the treatment of TTP, but the exact nature and duration of its impact on relapse has not yet been fully established,” Dr. Sun said during her presentation. “The goal of our study was to identify risk factors at presentation for subsequent TTP relapse and to characterize the impact of rituximab on relapse in the setting of increased use of this drug for TTP in the past decade or so.”
The study consecutively enrolled 124 patients who presented with acute TTP at one of five academic medical centers between 2004 and 2017. The median age at presentation was 42 years (range = 31-52 years), and most patients (104; 84%) presented with de novo disease.
Of the 124 patients enrolled, 60 (48%) received rituximab, and the authors observed an “unsurprisingly steady increase” in the proportion of patients who were treated with rituximab during the study period. The drug was administered at a median of 12 days (range = 7-24 days) after presentation.
Thirty-four patients in the entire cohort (27%) experienced disease relapse at a median of 1.96 years (range = 1.05-4.07 years) after presentation. Eight patients (7.3%) died within 90 days of presentation, most frequently due to infections or cardiac arrest. Dr. Sun noted that these patients had a delay to diagnosis and start of plasma exchange therapy.
The baseline characteristics between patients who did and did not receive rituximab were similar, she reported, “with the exception that patients who received rituximab had a more severe and refractory disease course, lower platelet count at day 4 [after presentation], a higher reticulocyte count, and more plasma exchange procedures.” (P values for these comparisons were not reported.)
In a Kaplan-Meier survival analysis, the researchers found that patients treated with rituximab had a significantly lower relapse risk at one year after presentation, compared with patients who did not receive rituximab (p=0.01). However, at five years of follow-up, the relapse-free survival curves converged, with no difference over time (p=0.45).
The median time to relapse among all patients was 1.96 years (range = 1.08-4.06 years) and was nearly three times longer in the rituximab-treated group than the non-rituximab-treated group (3.71 years [range = 1.75-4.93 years] vs. 1.33 years [0.43-2.35 years]; p value not reported).
After adjusting for follow-up time, time from presentation to rituximab administration, and the waning effect of rituximab over time, the researchers identified the following factors as predictors of relapse:
- presenting with TTP relapse (hazard ratio [HR] = 3.05; 95% CI 1.4-6.6; p=0.005)
- age <25 years (HR=2.94; 95% CI 1.2-7.2; p=0.018)
- non-O blood group (HR=2.11; 95% CI 1.03-4.3; p=0.041)
While rituximab on the day of administration was associated with a decreased relapse risk (HR=0.85; 95% CI 0.03-0.68; p=0.014), this effect diminished over time. The risk for relapse increased by 0.2 percent per day following administration, until about 2.6 years, when the risk of relapse became equivalent to that in non-rituximab-treated patients.
“One of the questions in our field is whether timed retreatment or maintenance with rituximab (which is accepted practice in other hematologic conditions) should be considered for patients with TTP in remission,” Dr. Sun noted. “[These data] potentially provide support for the idea of maintenance rituximab dosing within a two- to three-year timeframe.”
The study’s findings are limited by its retrospective design, non-standardized treatment approach, and potential selection bias. “Although our data did not directly address whether patients at higher risk for relapse derive more benefit from rituximab, we see this work as a starting point for risk-stratifying patients with TTP for the use of rituximab and other immunomodulatory agents,” Dr. Sun concluded. “However, before [the risk factors identified in our study] are used to guide any treatment decisions, [they] will need to be evaluated prospectively in future studies.”
The authors report no relevant conflicts of interest.
Sun L, Mack JP, Li A, et al. Predictors of relapse and efficacy of rituximab in autoimmune thrombotic thrombocytopenic purpura (TTP): a multi-institutional registry-based analysis. Abstract #375. Presented at the 2018 ASH Annual Meeting, December 2, 2018; San Diego, CA.