CD44v6, a target for novel antibody treatment approaches, is frequently expressed in multiple myeloma and associated with deletion of chromosome arm 13q.
OBJECTIVE
Despite recent advances in the treatment of multiple myeloma (MM), this disease remains incurable in the majority of patients. Therefore, innovative treatment strategies are mandatory. Bivatuzumab mertansine is a novel cytotoxic immunoconjugate specifically targeting the CD44 splice variant CD44v6. To investigate the applicability of this compound to clonal plasma cell disorders, we analyzed CD44v6 expression on malignant plasma cells from patients with multiple myeloma.


METHODS
Bone marrow samples from 57 patients with monoclonal gammopathy of undetermined significance (MGUS), MM, and plasma cell leukemia (PCL) were examined for CD44v6 expression by using flow cytometry (FACS) analysis. In addition, all samples were investigated by fluorescence in situ hybridization (FISH) with a specific probe for the chromosomal band 13q14.


RESULTS
In only 1 of 16 cases (6%) with MGUS and 1 out of 6 cases (17%) with stage I MM were plasma cells CD44v6 positive. In contrast, 43% of the cases with stage II/III MM or PCL expressed CD44v6. In these cases, CD44v6 expression was significantly correlated with chromosome 13q14 deletion as determined by FISH (p=0.02).


CONCLUSIONS
CD44v6 is frequently expressed in advanced, high-risk MM. CD44v6 expression correlates with chromosomal band 13q14 deletions, a well-known risk factor in MM. These results suggest that this epitope is a potential new target for monoclonal antibodies such as bivatuzumab mertansine.
Liebisch
Peter
P
Dept. of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
Eppinger
Susanne
S
Schöpflin
Christine
C
Stehle
Gerd
G
Munzert
Gerd
G
Döhner
Hartmut
H
Schmid
Mathias
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology*; D007952:Leukemia, Plasma Cell / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D010265:Paraproteinemias / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D047368:Tumor Burden / Q000276:immunology
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C112697:CD44v6 antigen; D006023:Glycoproteins; D018960:Hyaluronan Receptors