Efficacy of ocaratuzumab (AME-133v) in relapsed follicular lymphoma patients refractory to prior rituximab.

Lymphoma and Plasma Cell Disorders
Session Type and Session Title: 
General Poster Session, Lymphoma and Plasma Cell Disorders
Abstract Number: 


J Clin Oncol 30, 2012 (suppl; abstr 8081)
Jennifer L. Wayne, Kristen N. Ganjoo, Brad L. Pohlman, Sven De Vos, Ian W. Flinn, Nam H. Dang, Markus Y. Mapara, Mitchell R. Smith, Adrienne M. O'Reilly, Shashidhara Y. Marulappa, Vinay Kumar Jain; Mentrik Biotech, LLC, Dallas, TX; Stanford University, Palo Alto, CA; Cleveland Clinic, Cleveland, OH; University of California, Los Angeles Medical Center, Los Angeles, CA; Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, TN; University of Florida, Gainesville, FL; University of Pittsburgh, Pittsburgh, PA; Fox Chase Cancer Center, Philadelphia, PA

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Abstract Disclosures


Background: Ocaratzumab, previously known as AME-133v, is a humanized next-generation anti-CD20 monoclonal antibody. It has been optimized with a 13 to 20-fold increase in binding affinity to CD20 and improved binding to the low-affinity (F/F and F/V) polymorphisms of FcγRIIIa (CD16), which are thought to predict lower response rates and shorter duration of responses to rituximab. Methods: In a phase I dose escalation study in relapsed follicular lymphoma (FL) patients, ocaratuzumab was well-tolerated at doses up to 375 mg/m2 (Forero-Torres et al. CCR 2012). In a follow-on phase II trial, 44 patients with relapsed FL following prior rituximab and the low-affinity FcγRIIIa polymorphism (F-carriers) received 375 mg/m2 of ocaratuzumab weekly for 4 doses. In this study, overall response rate (ORR) was 36% and median progression free survival (PFS) was 91 weeks (Ganjoo et al. Haematologica 2011). Results: Amongst the 56 patients receiving 100 and 375 mg/m2 of ocaratuzumab, 8 patients had a previous time to progression of ≤ 180 days following their last rituximab treatment. These patients had a median of 2 prior rituximab treatments, (range 1-6 treatments), and median PFS following last treatment of 159 days. Five of the 8 patients showed a longer PFS after ocaratuzumab administration, compared with last rituximab treatment. All 5 patients expressed the homozygous low-affinity genotype of FcγRIIIa (F/F). At the time of study closure, 3 of the patients were still in remission (indicated by * in the table). Conclusions: This retrospective analysis suggests that ocaratuzumab may be non-cross-resistant to rituximab in patients with the low-affinity FcγRIIIa polymorphism. Prolonged PFS in selected patients following ocaratuzumab suggests that the increased binding affinity to CD16 and improved antibody-dependent cell-mediated cytotoxicity (ADCC) of this antibody is clinically relevant. As a single agent, ocaratuzumab may provide prolonged clinical benefit in relapsed FL patients and a clinical trial comparing ocaratuzumab to rituximab is in preparation.
No. of prior RTX treatments PFS after RTX (days) PFS after ocaratuzumab (days)
1 172 826*
2 159 636
1 97 434*
2 163 357*
3 103 257
6 180 168
2 116 119
2 176 91