Anti-CD16/CD30 bispecific antibody treatment for Hodgkin's disease: Role of infusion schedule and costimulation with cytokines

Citation
F. Hartmann et al., Anti-CD16/CD30 bispecific antibody treatment for Hodgkin's disease: Role of infusion schedule and costimulation with cytokines, CLIN CANC R, 7(7), 2001, pp. 1873-1881
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
CLINICAL CANCER RESEARCH
ISSN journal
1078-0432 → ACNP
Volume
7
Issue
7
Year of publication
2001
Pages
1873 - 1881
Database
ISI
SICI code
1078-0432(200107)7:7<1873:ABATFH>2.0.ZU;2-1
Abstract
The natural killer cell-activating anti-CD16/CD30 bispecific monoclonal ant ibody (BiMAb) had shown efficacy in a Phase I/II trial of refractory Hodgki n's disease (HD). To gain additional information on clinical efficacy and t o investigate the effects of different application schedules and the concom itant application of cytokines, we performed a second randomized pilot tria l 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 l-h infusio n every other day, In case of an objective response, retreatment was attemp ted after 4 weeks; in case of stable disease (SD), a second course was give n after prestimulation with interleukin 2 and followed by granulocyte macro phage colony-stimulating factor s.c. A total of 16 heavily pretreated patie nts received one to four BiMAb courses. Overall, we observed one complete r emission 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 cel ls 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 sum mary, this second trial confirmed the antitumor efficacy of this BiMAb agai nst HD and the minor toxicity of this BiMab. Coadministration of cytokines might contribute to an augmented antitumor activity, and additional clinica l trials are warranted to optimize this novel treatment modality.