Low-Dose Rituximab in Idiopathic Autoimmune Hemolytic Anemia.

Conventional therapy of warm autoimmune hemolytic anemia (WAIHA) include administration of corticosteroids and immunosuppressive agents, or splenectomy, whereas no effective treatment exists for cold hemagglutinin disease (CHD). A substantial proportion of patients with WAIHA do not respond to or relapse after corticosteroid therapy and may experience clinically relevant side effects. Favorable responses to rituximab at standard doses (375 mg/m² weekly for 4-6 courses) have been reported in both WAIHA and CHD, idiopathic or secondary, as well as in other autoimmune diseases, such as rheumatoid arthritis and primary immune thrombocytopenia. Recently, low dose (LD) rituximab (100 mg fixed dose weekly for 4 courses) has been proven effective in patients with autoimmune cytopenias, particularly immune thrombocytopenia.

To evaluate the safety, activity and the duration of the response of LD rituximab associated with standard oral prednisone (PDN) as first line therapy in newly diagnosed WAIHA and CHD, and as second line therapy in WAIHA relapsed after standard oral PDN.

In this single-arm prospective pilot study, LD-rituximab was administered at 100 mg fixed dose weekly on days +7, +14, +21, +28 along with standard oral PDN (1 mg/kg/die p.o. from day +1 to + 30, followed by quick tapering: 10 mg/week until 0.5/mg/kg/die, then 5 mg/week until stop). Complete and partial initial responses (iCR and iPR)) were defined as Hb ≥ 12 g/dL and ≥ 10 g/dL at month +2 from the beginning of therapy, respectively; sustained response (SR) was defined as Hb ≥ 10 g/dL at month +6 and +12, in the absence of any treatment.

Twelve patients (6 female, 6 male; median age 49 yrs, range 28-65) were enrolled. A iCR and iPR were observed in 6 and 4 out of 12 patients, respectively; the median Hb level increased from 9.9 g/dL (range 6.1-12.3) at enrolment to 12.3 g/dL (range 9.5-14.9) at month +2. A SR at month +6 was observed in 7 out of 7 evaluable patients, and in the first 2 patients enrolled at month +12. No side effects or serious adverse events were observed. For 9 relapsed AIHA patients laboratory data (Hb, LDH, reticulocytes) and steroid administration were available before LD rituximab treatment: a lower cumulative dose (roughly 50%) of steroid was administered to patients during LD rituximab study compared with previous therapy, without significant differences in the general trend of Hb, LDH, and reticulocytes.

These preliminary results seem to indicate that the addition of LD rituximab to standard corticosteroid therapy is a feasible and active treatment in AIHA. Data on SR are intriguing, particularly regarding the possible steroid sparing effect of LD rituximab, but need to be confirmed in larger survey and after longer follow up.

No relevant conflicts of interest to declare.