FCGR3A and FCGR2A polymorphisms may not correlate with response to alemtuzumab in chronic lymphocytic leukemia.
The in vivo mechanism of action of alemtuzumab (anti-CD52; Campath-1H) remains unclear. With rituximab, FCGR3A and FCGR2A high-affinity polymorphisms have been associated with clinical response in lymphoma but not in CLL, suggesting potential divergent mechanisms of action between these 2 diseases. Herein, we examined FCGR3A (V/V, n = 4; V/F, n = 10; F/F, n = 19) and FCGR2A (A/A, n = 5; H/A, n = 22; H/H, n = 6) polymorphisms in 36 patients with relapsed CLL who were treated with thrice-weekly alemtuzumab for 12 weeks to assess the potential influence these high-affinity FcgammaR receptor polymorphisms had on response to alemtuzumab. Response to alemtuzumab was similar regardless of FCGR3A polymorphism (V/V, 25%; V/F, 40%; F/F, 32%) or FCGR2A polymorphism (A/A, 40%; H/A, 32%; H/H, 33%). These findings indicate that FCGR3A and FCGR2A polymorphisms may not predict response to alemtuzumab in CLL. Future studies examining larger cohorts of alemtuzumab-treated patients with CLL will be required to definitively determine the predictive value of specific FCGR polymorphisms to treatment response.
Lin
Thomas S
TS
Department of Medicine, Division of Hematology-Oncology, The Ohio State University, Columbus 43210, USA.
Flinn
Ian W
IW
Modali
Rama
R
Lehman
Teresa A
TA
Webb
Jennifer
J
Waymer
Sharon
S
Moran
Mollie E
ME
Lucas
Margaret S
MS
Farag
Sherif S
SS
Byrd
John C
JC
D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000235:genetics*; D017452:Receptors, IgG / Q000235:genetics*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; C445323:FCGR2A protein, human; C496124:FCGR3A protein, human; D017452:Receptors, IgG; D000074323:Alemtuzumab