Wolfgang Miesbach: Rituximab Dose Optimization in iTTP – Why Standard Dose is Preferred?
Wolfgang Miesbach, Professor of Medicine at Frankfurt University Hospital, shared on LinkedIn:
“ASH25 Data: Rituximab Dose Optimization in iTTP. Exciting results from Mari Thomas and colleagues on rituximab dosing strategies in immune thrombotic thrombocytopenic purpura (iTTP)—the first randomized trial comparing low-dose versus standard-dose preemptive rituximab in this life-threatening condition.
The Clinical Problem
iTTP remains devastating, with 74% relapse rates at 7 years in patients with persistent severe ADAMTS13 deficiency. While preemptive rituximab has transformed outcomes, optimal dosing remained uncertain—until now.
Study Design
- Standard dose: 375 mg/m² weekly × 4 weeks
- Low dose: 200 mg weekly × 4 weeks
- Population: 68 adults with iTTP in remission, ADAMTS13 activity ≤15%
- Primary objective: Non-inferiority for time to retreatment
Efficacy Outcomes and median time to retreatment:
Low dose: 19.7 months
Standard dose: 20.1 months
HR 0.93 (95% CI: 0.56-1.53), p=0.799
ADAMTS13 normalization: 31 days (low dose) vs. 21 days (standard dose)—HR 0.73, p=0.187
Duration of ADAMTS13 response: 17.3 months vs. 19.1 months (p=0.864)
Clinical relapse rates (remarkably low in both arms):
– Low dose: 6.3%
– Standard dose: 0%
Critical Treatment Effect Dynamics
Non-constant treatment effect: More retreatments observed in the first 12 months with low-dose rituximab
After 12 months: Curves converge—suggesting early vulnerability with dose reduction
Immune Reconstitution
B cell return: 12.2 months (low dose) vs. 16.1 months (standard dose), p=0.151
Safety Profile: Reassuring News
- Infusion reactions: Predominantly mild with both regimens
- Delayed adverse effects: Well-managed across both arms
- Pre-emptive rituximab remains safe, effective, and well-tolerated with repeated dosing
Results
This rigorous trial demonstrates that while low-dose rituximab shows activity, standard dosing (375 mg/m² weekly × 4) provides more consistent protection against early ADAMTS13 relapse—a critical insight for optimizing long-term management.
Recommendation: Standard-dose remains the preferred preemptive regimen in iTTP.”
Read more from Wolfgang Miesbach on Hemostasis Today.
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