TY - JOUR
T1 - Phase I multidose-escalation study of the anti-CD19 maytansinoid immunoconjugate SAR3419 administered by intravenous infusion every 3 weeks to patients with relapsed/refractory B-cell lymphoma
AU - Younes, Anas
AU - Kim, Stella
AU - Romaguera, Jorge
AU - Copeland, Amanda
AU - Farial, Silvanade De Castro
AU - Kwak, Larry W.
AU - Fayad, Luis
AU - Hagemeister, Frederick
AU - Fanale, Michelle
AU - Neelapu, Sattva
AU - Lambert, John M.
AU - Morariu-Zamfir, Rodica
AU - Payrard, Sandrine
AU - Gordon, Leo I.
PY - 2012/8/1
Y1 - 2012/8/1
N2 - Purpose: We determine the maximum-tolerated dose (MTD), pharmacokinetics, safety, and preliminary efficacy of SAR3419, an antibody-drug conjugate targeting CD19, in a first-in-man phase I clinical trial in patients with relapsed lymphoma. Patients and Methods: Patients with relapsed CD19+ B-cell lymphoma were treated with escalating doses of SAR3419 given by intravenous infusion once every 21 days. Results: Thirty-nine patients were treated on seven dose levels ranging from 10 to 270 mg/m 2. The median number of prior treatment regimens was four (range, 1 to 9), and 11 patients had prior autologous or allogeneic stem-cell transplantation. The dose-limiting toxicities were reversible severe blurred vision associated with microcystic epithelial corneal changes reported in six patients and neuropathy in one patient. The MTD was 160 mg/m 2 once every 21 days. Hematologic and hepatic toxicities were predominantly grade 1 or 2 in severity. A total of 35 patients have completed at least two cycles of treatment and were evaluable for tumor response. Twenty-six patients (74%) demonstrated reduction in their tumor size; six of those patients achieved partial or complete remissions. Seven (47%) of 15 patients with rituximab-refractory disease demonstrated reduction in their tumor sizes. The pharmacokinetic profile of SAR3419 is characterized by linear kinetics, low clearance from 0.2 to 0.6 L/d/m 2, and an elimination half-life in the range of 3 to 7 days. Conclusion: Using an every 3-week-schedule of SAR3419 for six cycles, the MTD is 160 mg/m 2. SAR3419 can be safely administered to patients with relapsed B-cell lymphoma and demonstrates promising clinical activity, including patients who were refractory to rituximab.
AB - Purpose: We determine the maximum-tolerated dose (MTD), pharmacokinetics, safety, and preliminary efficacy of SAR3419, an antibody-drug conjugate targeting CD19, in a first-in-man phase I clinical trial in patients with relapsed lymphoma. Patients and Methods: Patients with relapsed CD19+ B-cell lymphoma were treated with escalating doses of SAR3419 given by intravenous infusion once every 21 days. Results: Thirty-nine patients were treated on seven dose levels ranging from 10 to 270 mg/m 2. The median number of prior treatment regimens was four (range, 1 to 9), and 11 patients had prior autologous or allogeneic stem-cell transplantation. The dose-limiting toxicities were reversible severe blurred vision associated with microcystic epithelial corneal changes reported in six patients and neuropathy in one patient. The MTD was 160 mg/m 2 once every 21 days. Hematologic and hepatic toxicities were predominantly grade 1 or 2 in severity. A total of 35 patients have completed at least two cycles of treatment and were evaluable for tumor response. Twenty-six patients (74%) demonstrated reduction in their tumor size; six of those patients achieved partial or complete remissions. Seven (47%) of 15 patients with rituximab-refractory disease demonstrated reduction in their tumor sizes. The pharmacokinetic profile of SAR3419 is characterized by linear kinetics, low clearance from 0.2 to 0.6 L/d/m 2, and an elimination half-life in the range of 3 to 7 days. Conclusion: Using an every 3-week-schedule of SAR3419 for six cycles, the MTD is 160 mg/m 2. SAR3419 can be safely administered to patients with relapsed B-cell lymphoma and demonstrates promising clinical activity, including patients who were refractory to rituximab.
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U2 - 10.1200/JCO.2011.39.4403
DO - 10.1200/JCO.2011.39.4403
M3 - Article
C2 - 22753910
AN - SCOPUS:84864544136
SN - 0732-183X
VL - 30
SP - 2776
EP - 2782
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 22
ER -