CD20-immunotargeting of malignant melanoma.

Abstract

8565 Background: Melanomas, like other malignancies, contain distinct subpopulations of cells. These subpopulations provide the cellular basis for the complex biology of the disease including phenomena such as self-renewal, differentiation, and tumor initiation, maintenance and progression, and may have major translational impact. In melanoma, several subpopulations - some with stem cell-like characteristics - have been described including one expressing CD20. Methods: multispectral imaging; xenografting onto CB17 SCID and NOD/SCID/γc-/- mice; adjuvant treatment with rituximab in 9 stage IV (M1a-c) melanoma patients, of whom the majority had received multiple prior systemic therapies. Induction treatment at 375 mg/m2 qw for 4 wk followed by maintenance therapy at 375 mg/m2 every 8 wk. Treatment was stopped after 2 years or with development of progressive disease. Results: We show by multispectral imaging that CD20 can be expressed on melanoma cells in human tumor samples. Furthermore, western blot analysis revealed expression of CD20 in lysates from human melanoma xenografts after serial in vivo passaging, consistent with environmental induction. Growth of human melanoma xenografts in two different preclinical in vivo models was significantly reduced by systemic administration of a monoclonal anti-CD20 antibody. Based on these results, we initiated a small phase II pilot trial on adjuvant treatment with an anti-CD20 antibody in stage IV (M1a-c) melanoma patients. Treatment was well tolerated. After 2 years, 6 patients (66%) are still disease-free, the 2 years OS rate was 100%. 2 patients died thereafter (22%). With a mean DFI and OS of 27+ months anti-CD20 treated patients show a > 3-fold longer median DFI and a somewhat higher median OS as compared to data obtained from large prospective clinical trials and retrospective analyses of stage IV melanoma patient cohorts, that have been treated by complete metastasectomy. Conclusions: Though patient numbers included in the present clinical study are too small for definitive conclusions, immunotargeting of CD20 may represent a first example of the potential therapeutic value of targeting melanoma subpopulations. Application of these initial clinical observations in larger trials is under way. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche