What data supports the use of sirolimus in refractory ITP?¶
Answer: Sirolimus (an mTOR inhibitor) is an off-label, second-line option for relapsed/refractory ITP, supported by small prospective single-arm trials, retrospective cohorts, and one randomized pediatric trial.
Adult data:
- Prospective open-label single-arm study, 86 patients: ORR 85% at 3 months, 70% at 6 months, 65% at 12 months. Responses were better in patients under 40 or with steroid-dependent disease, and responders showed reduced Th2/Th17 cells with increased Tregs and M-MDSCs.
- Single-center study, 20 patients: ORR 60% at 3 months.
- Multicenter cohort, 45 patients: 38/45 responded, 28 in complete response at end of follow-up.
Pediatric data:
- RCT of sirolimus vs cyclosporine: both produced a significant platelet increase, with a ~50% response rate.
Our experience: better responses in AYA (adolescent and young adult) patients and those with T-cell abnormalities on flow, even if not clonal. Typical dose is 2–4 mg/day, though responses have been seen at doses as low as 1 mg.