Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial

Abstract

Key Points Sirolimus monotherapy is a safe and effective steroid-sparing agent, improving autoimmune cytopenias in highly refractory patients. Sirolimus is particularly active in ALPS and should be an early therapy option for patients who require chronic therapy.

Precision treatment with sirolimus in a case of activated phosphoinositide 3-kinase δ syndrome

“…cytopenias in PID conditions including common variable immunodeficiency and autoimmune lymphoproliferative syndrome [5,6].…”

Hyperactive mTOR pathway promotes lymphoproliferation and abnormal differentiation in autoimmune lymphoproliferative syndrome

“…Interestingly, clinical studies have shown that rapamycin but not MMF treatment of patients with ALPS efficiently reduced lymphoproliferation and numbers of circulating DNT cells. [11][12][13] Although it is not clear whether rapamycin affects expansion or induces apoptosis of DNT cells or both, 14 its therapeutic efficiency suggests specific signaling requirements of DNT cells.…”

Evolution of disease activity and biomarkers on and off rapamycin in 28 patients with autoimmune lymphoproliferative syndrome

“…3 The remarkable efficacy as a second-line agent for this indication was confirmed in a recent prospective study including a further 9 ALPS-FAS patients. 4 Here, we analyze aspects of rapamycin therapy that have so far not been addressed including first-versus second-line therapy, comprehensive biomarker responses, and the consequences of stopping rapamycin by reporting our experience in 28 ALPS-FAS patients.…”

“…activated PI3K delta syndrome 11 ), the rapamycin response in these diseases is much more variable. 4 At present, we therefore advocate first-line rapamycin only in ALPS-FAS patients. Third, we present new observations relevant for the guidance of long-term therapy.…”

“…Christian Klemann, 1,2* Myrian Esquivel, 3,4* Aude Magerus-Chatinet, 3,5 Myriam R. Lorenz, 6,7 Ilka Fuchs, 1 Nathalie Neveux, 8 Martin Castelle, 4 Jan Rohr, 1,2 Claudia Bettoni da Cunha, 9 Martin Ebinger, 10 Robin Kobbe, 11 Bernhard Kremens, 12 Florian Kollert, 13 Eleonora Gambineri, 14 Kai Lehmberg, 15 3,4,20 Alain Fischer, 3,4,21 Frederic Rieux-Laucat, 3,5 Stephan Ehl, …”