A phase II multicenter study of the anti-CD19 antibody drug conjugate coltuximab ravtansine (SAR3419) in patients with relapsed or refractory diffuse large B-cell lymphoma previously treated with rituximab-based immunotherapy

Marek Trnĕný, Gregor Verhoef, Martin Js Dyer, Dina Ben Yehuda, Caterina Patti, Miguel Canales, Andrés Lopez, Farrukh T Awan, Paul G Montgomery, Andrea Janikova, Anna M Barbui, Kazimierz Sulek, Maria J Terol, John Radford, Anna Guidetti, Massimo Di Nicola, Laure Siraudin, Laurence Hatteville, Sandrine Schwab, Corina OpreaAlessandro M Gianni

Research output: Contribution to journalArticle

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-chemotherapy. 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 coltuximab 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 disorders occurred in 15 patients (25%); all were grade 1-2 and none required a dose modification. Coltuximab ravtansine monotherapy was well tolerated and resulted in moderate clinical responses in pre-treated patients with relapsed/refractory diffuse large B-cell lymphoma. (Registered at: clinicaltrials.gov identifier: 01472887).

Original languageEnglish
Pages (from-to)1351-1358
Number of pages8
JournalHaematologica
Volume103
Issue number8
DOIs
Publication statusPublished - Aug 2018

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Lymphoma, Large B-Cell, Diffuse
Immunotherapy
Multicenter Studies
Anti-Idiotypic Antibodies
Pharmaceutical Preparations
Confidence Intervals
Asthenia
Rituximab
SAR 3419
Nausea
Abdominal Pain
Population
Disease-Free Survival
Fatigue
Disease Progression
Diarrhea
Safety
Drug Therapy
Survival

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A phase II multicenter study of the anti-CD19 antibody drug conjugate coltuximab ravtansine (SAR3419) in patients with relapsed or refractory diffuse large B-cell lymphoma previously treated with rituximab-based immunotherapy. / Trnĕný, Marek; Verhoef, Gregor; Dyer, Martin Js; Ben Yehuda, Dina; Patti, Caterina; Canales, Miguel; Lopez, Andrés; Awan, Farrukh T; Montgomery, Paul G; Janikova, Andrea; Barbui, Anna M; Sulek, Kazimierz; Terol, Maria J; Radford, John; Guidetti, Anna; Di Nicola, Massimo; Siraudin, Laure; Hatteville, Laurence; Schwab, Sandrine; Oprea, Corina; Gianni, Alessandro M.

In: Haematologica, Vol. 103, No. 8, 08.2018, p. 1351-1358.

Research output: Contribution to journalArticle

Trnĕný, M, Verhoef, G, Dyer, MJ, Ben Yehuda, D, Patti, C, Canales, M, Lopez, A, Awan, FT, Montgomery, PG, Janikova, A, Barbui, AM, Sulek, K, Terol, MJ, Radford, J, Guidetti, A, Di Nicola, M, Siraudin, L, Hatteville, L, Schwab, S, Oprea, C & Gianni, AM 2018, 'A phase II multicenter study of the anti-CD19 antibody drug conjugate coltuximab ravtansine (SAR3419) in patients with relapsed or refractory diffuse large B-cell lymphoma previously treated with rituximab-based immunotherapy', Haematologica, vol. 103, no. 8, pp. 1351-1358. https://doi.org/10.3324/haematol.2017.168401
Trnĕný, Marek ; Verhoef, Gregor ; Dyer, Martin Js ; Ben Yehuda, Dina ; Patti, Caterina ; Canales, Miguel ; Lopez, Andrés ; Awan, Farrukh T ; Montgomery, Paul G ; Janikova, Andrea ; Barbui, Anna M ; Sulek, Kazimierz ; Terol, Maria J ; Radford, John ; Guidetti, Anna ; Di Nicola, Massimo ; Siraudin, Laure ; Hatteville, Laurence ; Schwab, Sandrine ; Oprea, Corina ; Gianni, Alessandro M. / A phase II multicenter study of the anti-CD19 antibody drug conjugate coltuximab ravtansine (SAR3419) in patients with relapsed or refractory diffuse large B-cell lymphoma previously treated with rituximab-based immunotherapy. In: Haematologica. 2018 ; Vol. 103, No. 8. pp. 1351-1358.
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T1 - A phase II multicenter study of the anti-CD19 antibody drug conjugate coltuximab ravtansine (SAR3419) in patients with relapsed or refractory diffuse large B-cell lymphoma previously treated with rituximab-based immunotherapy

AU - Trnĕný, Marek

AU - Verhoef, Gregor

AU - Dyer, Martin Js

AU - Ben Yehuda, Dina

AU - Patti, Caterina

AU - Canales, Miguel

AU - Lopez, Andrés

AU - Awan, Farrukh T

AU - Montgomery, Paul G

AU - Janikova, Andrea

AU - Barbui, Anna M

AU - Sulek, Kazimierz

AU - Terol, Maria J

AU - Radford, John

AU - Guidetti, Anna

AU - Di Nicola, Massimo

AU - Siraudin, Laure

AU - Hatteville, Laurence

AU - Schwab, Sandrine

AU - Oprea, Corina

AU - Gianni, Alessandro M

N1 - Copyright© 2018 Ferrata Storti Foundation.

PY - 2018/8

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N2 - 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-chemotherapy. 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 coltuximab 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 disorders occurred in 15 patients (25%); all were grade 1-2 and none required a dose modification. Coltuximab ravtansine monotherapy was well tolerated and resulted in moderate clinical responses in pre-treated patients with relapsed/refractory diffuse large B-cell lymphoma. (Registered at: clinicaltrials.gov identifier: 01472887).

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