P1482: recombinant erythropoietin in autoimmune hemolytic anemia with inadequate reticulocytosis: a single center prospective study

Topic: 28. Enzymopathies, membranopathies and other anemias Background: autoimmune hemolytic anemia (AIHA) is a rare hemolytic disorder mediated by autoantibodies with or without complement (C) activation. Bone marrow (BM) response may be insufficient to compensate hemolysis as demonstrated by inadequate reticulocytosis or inappropriately low endogenous erythropoietin (EPO). In retrospective series the use of recombinant (r)EPO was effective in increasing Hb levels in about 70% of patients irrespective of AIHA type. Aims: to prospectively evaluate the efficacy and safety of rEPO in AIHA patients with inadequate BM compensation. Methods: we prospectively included 35 patients with an established AIHA diagnosis, hemoglobin (Hb) <= 100 g/L and bone marrow responsiveness index (BMRI) < 121 who received rEPO at a single center in Milan, Italy, from January 2019 until the time of writing. Hematologic parameters, including EPO and BM evaluation at baseline, and AIHA type (warm, cold, mixed and atypical) were recorded. Responses were evaluated at 15, 30, 90 and 180 days from rEPO start and were classified as partial (PR, for Hb increase >= 20 g/L or Hb >= 100 g/L) or complete (CR, for Hb >= 120 g/L). Transfusion need was also systematically registered. Adverse events were collected and graded according to CTCAE v. 5. Results: 35 AIHA patients were included: 12 warm (WAIHA), 18 cold (CAD) and 5 mixed or atypical. At rEPO start, the median time from diagnosis was 16 months (range 0;346 months) and 92% of patients had been already treated with a median of 2 therapy lines (0;6). Median Hb was 76 g/L (32;100) and reticulocyte counts (Ret) 121 x10^9/L (10;266), resulting in a median BMRI of 76 (3;120). Median EPO serum levels were 56 IU/L (11;457). The following rEPO were used: epoetin alfa (85%), zeta (9%) or darbepoetin alfa (6%); 91% of patients received concomitant treatment with steroids (86%), rituximab (12%), IVIG (17%), or other immunosuppressants (3%). As shown in Figure 1, overall response rate was 49% (CR 6%, PR 43%) at 15 days, 70% (CR 15%, PR 55%) at 30 days, 75% (CR 34%, PR 41%) at 90 days and 82% (CR 46%, 36% PR) at 180 days. Median delta change of Hb in the whole cohort was +13 g/L (-30;+68), 20 (-26;+99); +32 (-7;+109), and +38 (-17;+83) g/L at the various time points. Consistently, the rate of transfusion need decreased from 26% at rEPO start to 11% at 15 days, to 9% at 30 days, to 6% at 90 days and to 9% at 180 days. Only 1 patient (0.3%) did not achieve an ORR throughout the study, and 5 (14%) relapsed, of whom 2 at 90 days and 3 at 180 days. At last follow up, 26 (74%) had discontinued rEPO (median time on rEPO of 125 days, 1-1061) mainly due to persistent response in 22 (63%). Only 1 patient experienced a G3 pulmonary embolism during admission for severe pneumonia and AIHA relapse. Summary/Conclusion: in this prospective evaluation of rEPO in AIHA with inadequate BM compensation we confirm an efficacy in more than 70% of patients with rapid Hb increase of more than 10 g/L at 15 days and transfusion reduction, improving with continuing treatment. Further studies including a control cohort is needed to confirm this evidence. Figure 1Keywords: Erythropoietin, Autoimmune hemolytic anemia (AIHA), EPO, Erythropoieisis