Real world use of sutimlimab in patients with cold agglutinin disease: An international study
Abstract
Abstract Sutimlimab has demonstrated high efficacy in increasing hemoglobin levels and reducing markers of hemolysis in patients with cold agglutinin disease (CAD) in clinical trials. However, data on its real-world use are limited. We evaluated 54 patients treated with Sutimlimab through post-trial access or compassionate use programs in Austria, France, Germany, Italy, Japan, Spain, UK, and Australia. Past medical history, CAD treatments and laboratory parameters were collected at baseline and at weeks 2, 4, 8, 12, 16, and 24, and at months 12, 18, 24, after starting sutimlimab. Response was classified as partial (Hb >10 g/dL), complete (>12 g/dL), or no response. The median age was 66 years (range 45-88) and 31 (57%) patients were females. The direct antiglobulin test (DAT) was positive for C3 alone in 35 patients, for IgG and C3 in 8, and for IgM and C3 in 10. The median CA titer was 1:1,024 (range, 1:4 to >1:25,000). CAD bone marrow infiltrate was observed in 23 patients. Prior CAD treatments (median 3, 1-4) included corticosteroids (31), rituximab (40), and rituximab–bendamustine (12). Pre-Sutimlimab complications included 8 G≥ 3 infections and 12 thrombotic events. The median number of RBC transfusions in the 6 months pre-Sutimlimab was 2 (0–18). At baseline, median Hb was 8.4 g/dL (2.9–10.8), LDH 1.6× ULN (0.8–3.6), unconjugated bilirubin 1.9 mg/dL (0.8–7.49), and reticulocytes 107×10⁹/L (10–340). Sutimlimab was administered as monotherapy (n=42) or in combination with erythropoietin (8), corticosteroids (2), or both (2). The median follow-up was 28 months (6–81). Hb increased over time: +2.0 g/dL at 2 weeks, +2.7 g/dL at 4 weeks, and +3 g/dL at 8 weeks, followed by sustained levels up to 24 months. Overall response rates (PR + CR) were 78%, 75%, 84%, 85%, 86%, 80%, 77%, 84%, and 85% at the respective timepoints. An additional 14% of patients showed an Hb increase at week 2 and 18% at week 4. All but 7 patients became transfusion-independent. Sutimlimab was discontinued in 2 patients due to lack of response, in 1 due to overt Waldenström's macroglobulinemia, and in 7 based on their own decision with maintenance of good CAD control; 13 patients had an infection (G3 in 7, 1 H. influenzae pneumonia), 1 thrombosis (DVT of basilic vein), and 8 hemolytic exacerbations. At the last follow up only one patient had died due to progressive WM with sepsis. Sutimlimab confirmed to be an effective treatment in improving anemia and resolving transfusion dependence in more than 70% patients in the real world.
Article Details
Authors (36)
Bruno Fattizzo
1Dipartimento di Oncologia ed Emato-Oncologia, Università degli Studi di Milano, Milan, Italy
Elisa Sambruna
1University of Milan, Milan, Italy
Yoshitaka Miyakawa
3Department of Hematology, Saitama Medical University, Saitama, Japan
Marc Michel
5Department of Internal Medicine, Henri Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Est Créteil University, Créteil, France
Carlo Visco
University of Verona, Verona, Italy
Michael Fillitz
14Hanusch Krankenhaus, Department of Internal Medicine, Vienna, Austria
George Kannourakis
6Fiona Elsey Cancer Research Institute, Ballarat, Victoria Australia, Victoria, Australia
Maria Bruna Greve
7Ospedale di Reggio Calabria, Reggio Calabria, Italy
Moritz Kleemiss
8University of Bonn, Bonn, Germany
Joan Cid
7Hospital Clinic i Provincial de Barcelona, Barcelona, Spain
Andrea Patriarca
Therapeutic Innovation in Hematology, Hematology Unit, Azienda Ospedaliero-Universitaria Maggiore della Carità, Novara, Italy
Laura Pavan
5Hematology Unit , University of Padova, Padova, Italy
Arbana Dizdari
12AUSL Romagna, Ravenna, Italy
Nilla Maschio
33Oncoematologia Istituto Oncologico Veneto IOV-IRCCS, Padova, Italy
Antonella Sau
14Ospedale Santo Spirito, Pescara, Italy
Cinzia Bitetti
15ASM Matera, Matera, Italy
Luigi Curreli
16Ospedale di Oristano, Oristano, Italy
Dorela Lame
17Ospedale di Ancona, Ancona, Italy
Uros Markovic
Antonio Solimando
19University of Bari, Bari, Italy
Giacinto Luca Pedone
1University of Milan, Department of Oncology and Hemato-Oncology, Milan, Italy
Francesco Versino
1King's College Hospital NHS Foundation Trust, Haematology, London, United Kingdom
Marta Bortolotti
1Hematology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
Davide Rapezzi
22Ospedale di Cuneo, Cuneo, Italy
Vincenzo Sammartano
23Federico II University, Napoli, Italy
Nicola Tumedei
24University of Bologna, Bologna, Italy
Luana Fianchi
8Dipartimento Di Diagnostica Per Immagini, Fondazione Policlinico Universitario A. Gemelli, IRCCS- Università Cattolica del Sacro Cuore, Radioterapia Oncologica Ed Ematologia, Roma, Italy
Jahanzaib Khwaja
2Department of Haematology, University College London Hospital, London, United Kingdom
Antonio De Vivo
24University of Bologna, Bologna, Italy
Francesco Lanza
1AUSL ROMAGNA, Hematology Unit & Romagna Transplant Network, Ravenna, Italy
Fabrizio Vianello
27University of Padova, Padova, Italy
Esther Natalie Oliva
29London North West University Healthcare NHS Trust, Hematology Department, London, United Kingdom
Ulrich Jaeger
Medical University of Vienna, Vienna, Austria
Bernd Jilma
Medical University of Vienna, Vienna
Guillaume Moulis
8Toulouse University Hospital, Department of Internal Medicine, Toulouse, France
Wilma Barcellini
2Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Hematology Unit, Milan, Italy