Rituximab (R) for the Treatment of Autoimmune Hemolytic Anemia (AIHA) in Adults: An Analysis of Literature Reports in 92 Patients.
Authors: McDevitt Pamela W. , Fichtner Rachel , Frame James Norman 
Published: October 2019

Abstract
R is an anti-CD20 MoAb developed to treat B-cell malignancies. While R has been used to treat various autoimmune disorders including AIHA, a systematic review of reports of R to treat AIHA in adults has not been performed. We describe the clinical features and response to R in patients (pts)18 yrs or > with AIHA from PubMed English language citations and manufacturer (Genentech, Inc.) provided reports from 1998–2004. 39 reports (34 case reports, 5 case series) identified 92 pts (M 47, F 44, NS 1) with a mean age of 60.7 yr (range, 18–91). 1°/2° Warm (W) Ab, Cold (C) Ab (± associated disease), and mixed (C/W) AIHA was observed in 11/33, 46, and 2 pts, respectively. Associated disease included: lymphoproliferative (LPD)-(W: NHL 4, CLL 20; C: NHL 26, CLL 1, other 6; C/W: other 1), rheumatologic-(W:6), infectious-(W:2, C:1 with EBV); and other (W:3; C:2) disorders. Other baseline pre-R features included: mean Hgb 7.5 g/dl (range, 2.8–12); >45 pts with a Hgb < 10 g/dl; DAT (+): all W-AIHA; Cold Ab or agglutinin (+): all C-AIHA; both DAT/C Ab(+): C/W-AIHA; previously untreated 17%; prior splenectomy >11 patients; transfusion dependent 21%; and a mean of 2.6 (range, 1–8) prior immunosuppressive regimens. R was administered as 375 mg/m2 IV weekly X 4 in 83% and in other schedules (15%) for a mean of 3 doses (range, 2–8); cycle no. was not stated in 2% pts. R was administered alone in 52 pts and with IVIG 3, chemotherapy 13, or corticosteroids 27. The criteria for response to R included: CR [stable↑ Hgb by 2 or > g/dl or Hgb 12 or > g/dl and (−) W or C Ab or agglutinin, resolution of symptoms of anemia, transfusion independent]; PR (↑ Hgb by 2 or > g/dl or Hgb 10 or > g/dl but < 12 g/dl, and 50% ↓ in C Ab/agglutinin titers, + warm Ab, improvement in symptoms of anemia, transfusion independent); NR (failure to meet CR/PR). 83% were eligible for response determination: R monotherapy-CR 10, PR 22, NR 14; R+other regimen-CR 12, PR 10, NR 8. Pt. response by type of AIHA included: 1° W-Ab (CR 3, PR 1, NR 3), 2° W-Ab (CR 7, PR 14, NR 7), C-Ab ± associated disease (CR 11, PR 17, NR 12) and C/W (CR 1). In the total group, the Hgb increased a mean of 3.8 g/dl (range, −1.4–10.5). Hgb increased in CRs by 5.6 (range, 2.9–10.5), in PRs by 4.0 (0.7–8.1), and in NRs by 2.1(−1.4–9.5). The mean time to response/response duration among CR+PRs was 22 days (range, 5–120)/10.5 mo. (range, 1.5–42). Response duration was recorded as last f/u if the pt did not relapse. Re-treatment with R was reported in 17 pts after initial best reported response (1st cycle PR 14, NR 3) with R alone (9) or in combination with CTX + DEX (5), or IFN (3) achieving 12 PRs (R 5, R+C+D 5, R+IFN 2) and 5 NRs (R 4, R+IFN 1). Reported R toxicity (n): infusion-related (7), myalgia (1), pruritis (2) rash (1) Gr.4 WBC (2) hypotension (1) and headache (2). One pt died from a fungal infection 3 mo.after R therapy. In this report, R ± other agents was effective and well-tolerated producing a 71% response rate with clinically meaningful response durations. LPDs were reported in 63% of pts. Studies of R to prospectively assess treatment and response variables, particularly among pts with with W-Ab AIHA, are warranted.