CO031 | PREEMPTIVE RITUXIMAB IN ADAMTS13 RELAPSE DURING CLINICAL REMISSION OF IMMUNE THROMBOTIC THROMBOCYTOPENIC PURPURA: A MULTICENTER ITALIAN STUDY

A. Dedola^1|2, G. Carli³, C. Sartor¹, B. Scappini⁴, B. Cambò⁵, G. Marchesini³, A. Dizdari⁶, S. Pozzi⁷, P. Bernuzzi⁸, A. Merli⁹, C. Lucarelli⁴, F. Salvatore^1|2, D. Cavallina^1|2, N. Severi^1|2, F. Branzanti², F. Lanza⁶, A. Lucchesi¹⁰, F. Palandri¹ | ¹IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Italy; ²Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy; ³Hematology Unit, Ospedale San Bortolo, ULSS8 Berica, Vicenza, Italy; ⁴Hematology Department, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy; ⁵U.O.C. Ematologia e Centro Trapianti Midollo Osseo, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy; ⁶AUSL Romagna, Ospedale di Ravenna, Ravenna, Italy; ⁷Hematology Unit, Azienda USL-IRCSS di Reggio Emilia, Reggio Emilia, Italy; ⁸Hematology Unit, Department of Onco-Hematology, Guglielmo da Saliceto Hospital, Piacenza, Italy; ⁹U. O. C. Ematologia Infermi Rimini AUSL Romagna, Rimini, Italy; ¹⁰IRCCS Istituto Romagnolo per lo Studio dei Tumori IRST 'Dino Amadori', Meldola, Italy

Background and Aims. Immune thrombotic thrombocytopenic purpura (iTTP) is a rare hematologic disorder caused by immune-mediated ADAMTS13 deficiency. ADAMTS13 activity monitoring during remission enables early detection of biochemical relapse (ADAMTS13 activity <20% without hemolysis, anemia, or thrombocytopenia). In this setting, preemptive rituximab (RTX) is recommended, but real-world data are limited. The aim of this study was to evaluate the effectiveness of preventive RTX in iTTP with biochemical relapse and to identify predictors of relapse, including ADAMT13 activity kinetics.
Methods. We performed an observational study across nine Italian hematology centers, including iTTP patients (pts) treated with RTX for biochemical relapse. ADAMTS13 response was defined as activity ≥20% in two consecutive evaluations; ADAMTS13 complete response (CR) as ≥ lower limit of normal, corresponding to ≥60% in our laboratory (Cuker A et al. Blood 2021). Predictors of biochemical relapse included prior RTX or caplacizumab use, prior clinical relapse, RTX dose, and 12-month ADAMTS13 kinetics.
Results. Forty-nine pts were included; 22 had prior RTX and 24 caplacizumab. At biochemical relapse, median age was 48.8 years; median ADAMTS13 activity and inhibitor were 3% (IQR 0.5–7.1) and 1.8 BU/mL (IQR 0.9–5.4). RTX was used at a standard dose (375 mg/m² weekly x4 or x6) in 46 pts (93.9%); 3 pts received a lower flat dose (200 mg x4). Median follow-up was 33.6 months (mos); 5 infections occurred. Forty-six patients (93.9%) achieved an ADAMTS13 response, including 36 (73.5%) CR. Median ADAMTS13 activity increased progressively during follow-up: 50% (IQR 24.5–82.1) at fourth RTX; 60% (IQR 34–89.4) after 1 mo; 76% (IQR 55.7–88) after 3 mos; 79.5% (IQR 54–96) after 6 mos; and 78% (IQR 43–92.9) after 12 mos (Figure). Median time to best response was 5.0 months. Twenty responders (43.5%) experienced a second biochemical relapse (n.18, 90% after ≥1 year from RTX, median 34.8 mos). Prior RTX exposure (OR 3.67, p=0.047) and clinical relapses (OR 4.2, p=0.002) were associated with higher relapse risk. RTX retreatment was given in 19 points, with 18 responders. One clinical relapse occurred in a non-responder. Overall, 21pts experienced a biochemical/clinical relapse or failed to achieve response ≥1 year from RTX. Failure to achieve a complete ADAMTS13 response within 1 year was associated with a significantly higher risk of non-response or subsequent clinical or biochemical relapse (p=0.001).
Conclusions. Preemptive RTX is effective in iTTP pts with biochemical relapse, with no clinical relapses observed in responders. Pts with a refractory/relapsing disease are at higher relapse risk after preemptive RTX. Early ADAMTS13 activity dynamics identify pts who may benefit from intensified preemptive therapy, reinforcing the value of systematic ADAMTS13 monitoring.