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Poster Presentation
Safety and disease response to MEDI-551, an anti-CD19 antibody, in chronic lymphocytic leukemia patients previously treated with rituximab
  1. Andres Forero1,
  2. Mehdi Hamadani2,
  3. Thomas Kipps3,
  4. Michelle Fanale4,
  5. Antonio Cuneo5,
  6. Jaime Perez de Oteyza6,
  7. Douglas Gladstone7,
  8. Marc Andre8,
  9. Naresh Bellam1,
  10. Trishna Goswami9,
  11. Ramy Ibrahim9,
  12. Amy Schneider10,
  13. Meina Liang10,
  14. Steven Eck9,
  15. Nairouz Elgeioushi9,
  16. Ronald Herbst9 and
  17. Bruce D Cheson11
  1. Aff1 grid.265892.20000000106344187University of Alabama at Birmingham Birmingham AL USA
  2. Aff2 grid.268154.c0000000107455110West Virginia University Morgantown WV USA
  3. Aff3 grid.266100.30000000121074242Moores UCSD Cancer Center San Diego CA USA
  4. Aff4 grid.267308.80000000092062401University of Texas Houston TX USA
  5. Aff5 grid.416315.4Azienda Ospedaliera Universitaria Arcispedale Sant'Anna Ferrara Italy
  6. Aff6 grid.428486.4Centro Integral Oncologico Clara Campal Madrid Spain
  7. Aff7 grid.21107.350000000121719311Johns Hopkins University Baltimore MD USA
  8. Aff8 grid.411754.2CHU Mont-Godinne Yvoir Belgium
  9. Aff9 grid.418152.bMedImmune Gaithersburg MD USA
  10. Aff10 grid.418152.bMedImmune Gaithersburg CA USA
  11. Aff11 grid.411663.70000000089370972Georgetown University Hospital Washington DC MD USA

http://dx.doi.org/10.1186/2051-1426-1-S1-P43

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    Meeting abstracts

    Background

    The expression of CD19 on chronic lymphocytic leukemia (CLL) cells offers a novel therapy for relapsed CLL patients (pts) previously treated with rituximab. MEDI-551 is an affinity-optimized anti-CD19 Ab with enhanced Ab-dependent cellular cytotoxicity (ADCC) effector function.

    Methods

    Response and toxicity of single-agent MEDI-551 in multiply relapsed CLL pts with prior rituximab therapy was assessed in a phase 1/2 (ph 1/2), open-label, dose-escalation and expansion study. Combination therapy was assessed in an ongoing phase 2 (ph 2) study comparing MEDI-551 or rituximab+bendamustine in relapsed/refractory CLL pts. For the ph 1/2 study, B cell depletion was assessed with flow cytometry and BAFF biomarker analysis; response was assessed using the 2008 IWG criteria.

    Results

    In the ph 1/2 study, 26 CLL pts received ≥1 dose of MEDI-551. In the ph 2 study, 44 pts received study drug as of 20Mar2013. Loss of CD19 detection due to depletion and/or occupancy with MEDI-551 was rapid and apparent after cycle 1. B cell depletion occurred 1 day after dose 1 and was associated with increased serum BAFF concentrations. In the ph 1/2 study, of 21 MEDI-551-treated CLL pts evaluable for response, 5 achieved partial remission and 13 had stable disease. Commonly reported adverse events (AEs) in MEDI-551 pts were infusion-related reactions (IRRs; 62%), nausea (23%), pyrexia (23%), and neutropenia (23%) in the 26 ph 1/2 pts; in the 29 ph 2 pts, they were nausea (62%), IRRs (31%), pyrexia (28%), chills (28%), and fatigue (28%). 11 pts had ≥ grade 3 AEs in the ph 1/2 study and 16 in the ph 2. Common treatment-related AEs: IRRs (58%) and nausea (12%) in the ph 1/2; nausea (52%), IRRs (28%), chills (24%), and fatigue (24%) in the ph 2. Three treatment-unrelated AEs of general health deterioration (ph 1/2), subarachnoid hemorrhage (ph 1/2), and sepsis (ph 2), resulted in death.

    Conclusions

    MEDI-551 as a single agent demonstrated B-cell depletion, increased serum BAFF levels, clinical activity, and an acceptable risk-benefit profile in relapsed/refractory CLL pts. Preliminary results of the ongoing ph 2 study of MEDI-551+bendamustine demonstrated an acceptable safety profile.