PS1158 IBRUTINIB PLUS RITUXIMUB IN STEROID REFRACTORY AUTOIMMUNE HEMOLYTIC ANEMIA: ELABORATION OF TREATMENT APPROACH (ISRAEL): AN INTERIM ANALYSIS OF THE ROHS TRIAL

• DOI: 10.1097/01.hs9.0000562916.18980.8c
• Publication Date: 2019-06-17T13:28:28Z
• Authors: E. Nikitin; E. Dmitrieva; D. Morozov; A. Suvorova; J. Sveshnikova; G. Vyscub; I. Matveeva; T. Klitochenko; A. Shipaeva; M. Shirokova; O. Samoilova; K. Kaplanov; T. Konstantinova; I. Poddubnaya; V. Ptushkin
• Keywords: 0301 basic medicine; 03 medical and health sciences

Background: Autoimmune hemolytic anemia (AIHA) and pure red cell aplasia (PRCA) are well recognized autoimmune complications (AIC) of chronic lymphocytic leukemia (CLL). Both AIHA PRCA complicate patient management, have significant impact on quality life can be fatal. Ibrutinib is an irreversible inhibitor BTK ITK (interleukin‐2 inducible tyrosine kinase), mediating antibody dependent cellular cytotoxicity, which makes it attractive in treatment AIC the context CLL. We present a pre‐planned interim analysis multicentre trial evaluating efficacy ibrutinib AIC. Aims: The primary objective this study to evaluate (response rate its duration) combination with rituximab for steroid refractory patients Methods: ISRAEL open‐label, multicentre, single arm, two staged AIHA/PRCA underlying In stage I (induction) received 420 mg/day (9 weekly subsequent 3 monthly infusions); II (maintenance) – was only given until relapse, progression or unacceptable toxicity. Inclusion criteria included proven diagnosis CLL per iwCLL guidelines, presence clinically hemolysis positive direct antiglobulin test (DAT) case AIHA, erythroblastopenia, confirmed by immunohistochemical staining Glycophorin A platelet level >100.000/mkl PRCA, relapse after steroids, splenectomy refractoriness glucocorticosteroid hormones. Results: Thirty three been enrolled since February, 2017. median age 66 years (range 50 ‐ 82), 14 (42%) were female. 30 had PRCA. hemoglobin at day 1st infusion 8,2 g/dL 6,5 11,3). Twenty (66%) transfusion‐dependent. Five (15%) deletion 17p 8 (24%) 11q. Patients 2 1 6) lines prior AIC, including steroids (n = 31), 6), 3), RCD/R‐CVP 13), alemtuzumab 1), BR 7) other 8). At time reporting, 22 completed induction. duration 281 days 673). Adverse events reported from 31 participants (94%). Of 351 AEs, 321 (91,5%) graded as CTCAE grade (8,5%) >3. latter represented infections 7), neutropenia arrhythmias 4), arterial hypertension myalgias 3). Two cases sudden death reported. Response evident all patients. By 141 4 (21%) achieved DAT‐ve CR, 10 (53%) DAT+ve PR PR. All transfusion independence. CR 84 150, did not respond. CLL, assessed 225 IWCLL 2008 available 19 Seven (37%) one MRD‐negative case. Twelve (63%) classified PRs because residual bone marrow infiltration 12) along persistent splenomegaly 3) 2). No relapsed so far. Summary/Conclusion: demonstrated high activity safety profile IR corresponded published data.