BioOncology Watch Timely Information for Practicing Physicians
DECEMBER 1998 EFFECT OF CANCER ON IMMUNE FUNCTION Defective function of Langerhans cells (LC). Dr. Tadao Ishida and coworkers investigated the effect of tumor (D 459 and MethA sarcoma cells) in mice (6-8 week old BALB/c female mice) on the immune function of LC by utilizing FITC applied to skin as a presenting antigen. LC belong to the dendritic cell (DC) family, are derived from bone marrow B-lymphocytes, and are the major antigen presenting cells in the skin. Compared to control mice, tumor-bearing mice demonstrated a reduced migration of LC to lymph nodes (P<0.01) and a reduced capability of lymph node DC to stimulate primary T cell responses. These defects were: 1) observed at sites near and distant to tumor, 2) due to decreased numbers of mature LC (not to individual cell dysfunction), and 3) reversed partially by anti-VEGF treatments. Thus, malignant tumors are associated with systemic effects on mature LC production and inhibition of VEGF signaling may improve immune function in tumor-bearing hosts. (Ishida T, et al. J Immunol 1998, 161: 4842-4851) PALLIATION OF TRANSPLANTATION COMPLICATIONS Anti-B-cell antibody therapy of B-lymphoproliferative disorder (PTBCL). Dr. Malika Benkerrou and colleagues studied the use of the combination of two murine monoclonal anti-B-cell antibodies (anti-CD21 and anti-CD24) as therapy for 58 patients with PTBCL in an open multicenter trial. PTBCL is a severe complication (40%-90% mortality rate) of solid organ and bone marrow transplantation. A complete remission was achieved in 36 (61%) patients and relapse occurred in only 3(8%) patients. Survival was 46% with a median follow-up of 61 months (range 35.5 to 117 months). Results from this trial indicate the use of anti-B-cell antibodies is safe and effective therapy for PTBCL. (Benkerrou M, et al. Blood 1998, 92: 3137-3147) THERAPY FOR RELAPSED/REFRACTORY NON-HODGKIN'S LYMPHOMA (NHL) Rituximab (a chimeric anti-CD20 monoclonal antibody) therapy. The data from two recent trials of weekly outpatient rituximab (IDEC Pharmaceuticals Corp) therapy showed the response rates (CR + PR) for relapsing/refractory aggressive (54 patients) and indolent (166 patients) NHL patients were 31% and 48%, respectively. Time to progression was > 246 days (83-336+days) for the aggressive lymphoma group and 13.0 months (projected from a median follow-up of 11.8 months) for the indolent lymphoma group. The authors conclude that rituximab has activity in NHL patients and further investigation of combining this monoclonal antibody therapy with chemotherapy is warranted. (Coiffier B, et al. Blood 1998, 92: 1927-1932 and McLaughlin P, et al. J Clin Oncol 1998, 16: 2825-2833) Myeloablative 131I-anti-CD20 antibody therapy. Dr. Steven Liu et al report the long-term follow-up data from two trials of 29 relapsed NHL patients treated with myeloablative doses of 131I-anti-CD20 murine monoclonal antibody with autologous stem-cell rescue. Complete responses were achieved in 23 (79%) patients and unmaintained remissions were present in 14 patients with follow-up of 27+ to 87+months. Overall and progression-free survival rates were 68% and 42%, respectively, with a median follow-up of 42 months. Non-hematopoietic dose-limiting toxicity was reversible cardiopulmonary insufficiency and the only common late toxicity reported was elevated serum TSH levels (60% of patients). The investigators conclude that marrow ablative radioimmunotherapy is well-tolerated and effective in relapsing NHL patients. (Liu S, et al J Clin Oncol 1998, 16: 3270-3278) 131I-Lym-1 dose finding study. Dr. Gerald DeNardo and colleagues performed an open-label, multiple dose trial to assess the toxicity and efficacy of Lym - 1 (a murine monoclonal antibody against an epitope of HLA-DR10) labeled with iodine131 when administered to relapsed/refractory B-cell NHL patients. Twenty patients received a maximum of 4 doses of 131I-Lym-1 given 4 weeks apart. The maximum tolerated dose (MTD) was 100 mCi/m2 (3.7 GBq/m2) and the dose limiting toxicity was grade 3-4 thrombocytopenia. The response rate was 52% and there were 7 complete responses with median duration of 14 months (range, 2-35.5 months). All 3 entries in the MTD cohort achieved complete responses. This trial indicates that 131I-Lym-1 therapy is tolerable and effective in patients with NHL resistant to chemotherapy. (DeNardo GL, et al. J Clin Oncol 1998, 16: 3246-3256) CAMPATH-1H (a human anti-CD52 monoclonal antibody) therapy. Dr. J. Lundin and coworkers reported the results of CAMPATH-1H (Wellcome Research Laboratories) therapy in a multicenter phase II study of 50 previously treated low-grade NHL patients. Six (14%) B-cell lymphoma patients achieved a partial remission and 4 of 8 mycosis fungoides patients responded (2 complete remissions). The most pronounced antitumor effects were observed in blood, bone marrow, and skin. Severe lymphopenia occurred in all patients and neutropenia in 14 (28%) patients. Infectious complications were frequent (including 3 deaths). The authors conclude CAMPATH-1H therapy benefits some progressive low-grade NHL patients. However, treatment should be monitored closely due to the risk of infection. (Lundin J, et al. J Clin Oncol 1998, 16: 3257-3263)
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