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Anti-CD16/CD30 Bispecific Antibody Treatment for Hodgkin’s Disease

Role of Infusion Schedule and Costimulation with Cytokines¹

Department of Medicine [F. H., C. R., W. J., S. T., G. H., A. S., S. B., M. P.] and Institute of Medical Biometrics, Epidemiology, and Medical Informatics [J. K.], Saarland University Medical School D-66421 Homburg, Germany; Unidade de Oncologia, VP-2755 Cascais Portugal [L. d. C.]; and Biotest Pharma A.G., VD-63303 Dreieich, Germany [M. K.]

The natural killer cell-activating anti-CD16/CD30 bispecific monoclonal antibody (BiMAb) had shown efficacy in a Phase I/II trial of refractory Hodgkin’s disease (HD). To gain additional information on clinical efficacy and to investigate the effects of different application schedules and the concomitant application of cytokines, we performed a second randomized pilot trial using this BiMAb in patients with refractory HD. Patients received 4 x 25 mg HRS-3/A9 either as a continuous infusion for 4 days or as a 1-h infusion every other day. In case of an objective response, retreatment was attempted after 4 weeks; in case of stable disease (SD), a second course was given after prestimulation with interleukin 2 and followed by granulocyte macrophage colony-stimulating factor s.c. A total of 16 heavily pretreated patients received one to four BiMAb courses. Overall, we observed one complete remission and three partial remissions lasting 5–9 months (three of four of these responses occurred after continuous BiMAb infusion) and four cases of SD for 3 to >6 months. Interleukin 2 pretreatment before the second BiMAb course resulted in a significant increase of circulating natural killer cells in all five patients treated. This coincided with the conversion of two cases of SD into one complete remission and one partial remission. HRS-3/A9-related side effects consisted of mild fever in only six patients. In summary, this second trial confirmed the antitumor efficacy of this BiMAb against HD and the minor toxicity of this BiMAb. Coadministration of cytokines might contribute to an augmented antitumor activity, and additional clinical trials are warranted to optimize this novel treatment modality.

Commentary

Treating Hodgkin’s Disease with Bispecific Antibodies: Both Patients and Antibody Are Limiting

Richard I. Fisher
Clin. Cancer Res. 2001 7: 1835-1836. [Full Text] [PDF]

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