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

KLEMANN, CHRISTIAN; ESQUIVEL, MYRIAN; FISCHER, ALAIN; RIEUX-LAUCAT, FREDERIC; EHL, STEPHAN; RENSING-EHL, ANNE; NEVEN, BENEDICTE; MAGEROUS-CHATINET, AUDE; LORENZ, MYRIANM

HAEMATOLOGICA

FERRATA STORTI FOUNDATION

Lugar: Pavia, Italia; Año: 2017 vol. 102 p. 52 - 56

0390-6078

Chronic benign lymphoproliferation and autoimmune cytopenias are the main problems requiring treatment in FAS mutant patients with autoimmune lymphoproliferative syndrome (ALPS). Rapamycin has recently been shown to ameliorate both manifestations in 9 ALPS-(s)FAS patients. We extend this experience to 28 additional ALPS-(s)FAS patients, while focusing on the clinical and biomarker response in first and second line treated patients and after stopping rapamycin therapy. Two patients were treated for autoimmunity, 7 for lymphoproliferation and 18 for both manifestations. Rapamycin proved effective both as first- and second-line treatment with complete remission in 4/9 and 18/19 patients within 6 months, respectively, while the remaining 6 patients had partial remissions. sFASL, IL-10 and DNT levels were significantly reduced under rapamycin while vitamin B12 was not consistently altered. Rapamycin was well tolerated with no or mild side effects in most patients. In 6 patients in whom rapamycin was discontinued due to remission, side-effects or malcompliance, disease manifestations, sFASL and DNT fully relapsed within few weeks, but remission was achieved after re-initiation. Collectively, rapamycin was efficient as first and second-line therapy in ALPS-FAS patients. IL-10 and DNT most clearly mirrored the excellent clinical responsiveness to rapamycin, but discontinuation of rapamycin led to rapid relapse. Statement of equal authors? contribution: *the first 2 authors CK & ME and the last 2 authors ARE & BN have contributed equally to this work.