Page 115 - Haematologica August 2018

Non-Hodgkin Lymphoma
A phase II multicenter study of the anti-CD19 antibody drug conjugate coltuximab ravtansine (SAR3419) in patients with relapsed or refrac- tory diffuse large B-cell lymphoma previously treated with rituximab-based immunotherapy
Ferrata Storti Foundation
Marek Trnĕný,1 Gregor Verhoef,2 Martin JS Dyer,3 Dina Ben Yehuda,4 Caterina Patti,5 Miguel Canales,6 Andrés Lopez,7 Farrukh T Awan,8 Paul G Montgomery,9 Andrea Janikova,10 Anna M Barbui,11 Kazimierz Sulek,12 Maria J Terol,13 John Radford,14 Anna Guidetti,15,16 Massimo Di Nicola,15 Laure Siraudin,17 Laurence Hatteville,18 Sandrine Schwab,19 Corina Oprea18 and Alessandro M Gianni15,16
Haematologica 2018 Volume 103(8):1351-1358
1Charles University, General Hospital, Prague, Czech Republic; 2Department of Hematology, University Hospital, Leuven, Belgium; 3Ernest and Helen Scott Haematological Research Institute, University of Leicester, UK; 4Hadassah Medical Center, Jerusalem, Israel;
5PA Cervello EMAT, Palermo, Italy; 6Hospital la Paz, Madrid, Spain; 7Vall d’Hebron Research Institute, Barcelona, Spain; 8Ohio State University, Columbus, OH, USA; 9Boise VA Medical Center, Boise, ID, USA; 10Department of Hematology and Oncology, University Hospital Brno, Czech Republic; 11Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy; 12Wojskowy Instytut Medyczny, Warsaw, Poland; 13Hospital Clínico Universitario de Valencia, Health Research Institute INCLIVA, Spain; 14University of Manchester and The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, UK; 15Fondazione Istituto Nazionale Tumori, Milan, Italy; 16University of Milan, Italy; 17Lincoln, Paris, France; 18Sanofi R&D, Vitry sur Seine, France and 19Sanofi R&D, Chilly-Mazarin, France
ABSTRACT
This phase II, single-arm, multicenter study examined the efficacy and safety of coltuximab ravtansine (an anti-CD19 antibody drug conjugate) in 61 patients with histologically documented (de novo or transformed) relapsed or refractory diffuse large B-cell lymphoma who had previously received rituximab-containing immuno-chemother- apy. Patients had received a median of 2.0 (range 0-9) prior treatment regimens for diffuse large B-cell lymphoma and almost half (45.9%) had bulky disease (≥1 lesion >5 cm) at trial entry. Patients received coltux- imab ravtansine (55 mg/m2) in 4 weekly and 4 biweekly administrations until disease progression or unacceptable toxicity. Forty-one patients were eligible for inclusion in the per protocol population. Overall response rate (International Working Group criteria) in the per protocol population, the primary end point, was 18/41 [43.9%; 90% confidence interval (CI:) 30.6-57.9%]. Median duration of response, progression- free survival, and overall survival (all treated patients) were 4.7 (range 0.0-8.8) months, 4.4 (90%CI: 3.02-5.78) months, and 9.2 (90%CI: 6.57- 12.09) months, respectively. Common non-hematologic adverse events included asthenia/fatigue (30%), nausea (23%), and diarrhea (20%). Grade 3-4 adverse events were reported in 23 patients (38%), the most frequent being hepatotoxicity (3%) and abdominal pain (3%). Eye disor- ders occurred in 15 patients (25%); all were grade 1-2 and none required a dose modification. Coltuximab ravtansine monotherapy was well tol- erated and resulted in moderate clinical responses in pre-treated patients with relapsed/refractory diffuse large B-cell lymphoma. (Registered at: clinicaltrials.gov identifier: 01472887)
Correspondence:
trneny@cesnet.cz
Received: April 10, 2017. Accepted: May 3, 2018. Pre-published: May10,2018.
doi:10.3324/haematol.2017.168401
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/8/1351
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