Other monoclonal antibodies

A number of other unconjugated antibodies are being evaluated in clinical trials for follicular NHL (Table 53.1).

Alemtuzumab Alemtuzumab (Campath-1H) is a humanized anti-CD52 monoclonal antibody with activity in chronic lymphocytic leukemia as well as T-cell lymphomas; however, its single-agent activity in indolent B-cell NHL has been disappointing.7172

Epratuzumab Epratuzumab is a humanized IgG1 monoclonal antibody directed against the CD22 antigen, expressed on a variety of lymphomas. In a dose-escalation study of epratuzumab in 55 patients with indolent NHL, no dose-limiting toxicities were identified.73 The overall response rate was 24% in those with follicular histologies. In a subsequent trial, both epratuzumab and rituximab were administered using an empiric schedule with each weekly for 4 weeks. The response rate and duration were disappointing, suggesting that a inferior dose and schedule of this combination was used.74

Anti-CD80 (Galiximab) CD80 is an immune costimu-latory molecule present on the surface of NHL cells. Galiximab (IDEC-114) is a macaque-human chimeric anti-CD80 antibody with in vivo antilymphoma properties. In phase I trials, the antibody was well tolerated except for mild fatigue, nausea, and headaches. Moreover, single-agent activity was approximately 15%.75 Based on preclinical data suggesting synergy, a phase I/II study of the combination of galiximab and rituximab was conducted, and a response rate of 58.3% was reported.76 This combination has been evaluated as the initial therapy for patients with follicular lymphoma in a Cancer and Leukemia Group B phase II trial and results are pending.

Apolizumab Apolizumab (Hu1D10, Remitogen) is a humanized monoclonal antibody directed against a polymorphic determinant of HLA-DR, found on both normal B-cells and in about half of patients with lym-phoid malignancies. Limited activity and excessive toxicities have halted its development (U. Hegde, T. White, M. Stetler-Stevenson et al., unpublished data, 2002).77,78

Humanized anti-CD20 Several humanized anti-CD20 monoclonal antibodies are in clinical trials.79 Potential advantages are activation of different pathways enhancing cell kill, and a shorter infusion time. Whether there will be any clinical benefit remains to be determined.

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