P1616: emicizumab for the management of acquired hemophilia a

Topic: 33. Bleeding disorders (congenital and acquired) Background: Emicizumab (Emi) a bispecific antibody that mimics cofactor function of FVIII, is used for prophylaxis of bleeding in congenital hemophilia A. Data on its role in management of acquired hemophilia A (AHA) patients (pt) are confined to case reports and small descriptive cohort studies. Aims: To describe and compare outcomes of AHA pt treated with and without Emi. Methods: Medical records of AHA pt seen at Mayo Clinic within the last 10 years were reviewed. Pt were excluded if they were in remission at the time of first available FVIII activity (FVIII:C), lost to follow-up after starting immunosuppression (IST) or had a history of cirrhosis and variceal bleeding prior to diagnosis of AHA Results: 15 pts (10 female) with AHA were included. Median age at diagnosis was 69 yr (29-90). Median FVIII:C at diagnosis was 1% (0, 11). All pt presented with mucocutaneus or soft tissue bleeding of whom 10 required hospitalization. 8 pts required bypassing agents (BPA), at least 1 dose of rVIIa or APCC were used in 5 and 7 pts, respectively. Recombinant porcine factor VIII (rpFVIII) was used in one pt. Emi was used in 5 pt; 4 of these were hospitalized for bleeding while one received Emi prophylactically to minimize risk of rebleeding until resolution of FVIIIi (Figure 1). There was no difference in age, factor VIII:C and FVIIIi titer between patients receiving and not receiving Emi. Of 8 pt hospitalized for >1 day for hemostatic management there was no difference in duration of BPA or rpFVIII: 11.5(1,14) vs 5.5(1,10) days, (p=0.243) or hospital stay: 13(7,18) versus 8(6,10) days, (p=0.080) between pt not using vs using Emi respectively. Definite hemostatic benefit leading to shortened hospital stay was noted in 3 pt who had persistent bleeding with BPA/rpFVIII until use of Emi (figure 1 cases 1, 3 and 4). One pt (case 2) had a persistent FVIIIi despite 3 lines of IST with ongoing mild hematuria when BPA was discontinued. Hematuria improved after Emi was given. IST included prednisone (pred) as first line therapy in 13/15 pt and rituximab (ritux) alone in 2 pt. In the latter 2 pt, 1 was already on low dose pred at the time of FVIIIi diagnosis and pred was avoided in the other pt to optimize wound healing (Figure 1, case 4). Ritux was used concurrently with pred in the first and second line setting in 5 pts each. Cyclophosphamide (CTX) was used in 3 pts, twice as combination therapy with pred in the first line setting and once as second line therapy. Compared to pts not receiving Emi (n=4), those receiving Emi were on pred for a shorter duration: 125.5(86.0, 221) vs 67.0 (6.0, 74.0) days (p=0.007). There was no difference in use of ritux or CTX between the two groups. Of those achieving remission (n=13), one relapsed requiring hospitalization for management of bleeding (non-Emi cohort). Summary/Conclusion: Due to small sample size and heterogeneity in initial management prior to referral, we were not able to demonstrate a statistically significant reduction in hospitalization or effect on use of BPAs. However, pts receiving Emi received a shortened duration of pred. Emi was categorically beneficial in pt with persistent FVIIIi unable to tolerate further IST or pts with persistent bleeding despite typical hemostatic management. Future studies should focus on determination of the optimal cohort with AHA to consider Emi and its impact on hospitalization and use of BPAs.Keywords: Bleeding disorder, Factor VIII Inhibitor, Acquired hemophilia