In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 27, No. 15_suppl ( 2009-05-20), p. 8583-8583
Abstract:
8583 Antibody dependent cellular citotoxicity (ADCC) play a significant role in rituximab's anti-tumor activity. FcγRIIIa polymorphisms have been associated with clinical responses to rituximab. The predictive value of FcγRIIIa polymorphisms is lost when rituximab is combined with chemotherapy. Alternative assays to assess the immune system had not been studied in patients treated with rituximab plus chemotherapy. To this end, we prospectively studied the pre-treatment quality and function of PMNs and NK cells from pts with refractory/relapsed B-cell lymphomas in a Phase I/II trial. Forty-two B-cell lymphoma patients pts completed treatment. Demographics: 22M:20F; Median age = 61.8 (range 35–83); Patients received R (375 mg/m 2 /dose) on day 1 and LD (30 mg/m 2 /dose) on day 3 q21 day × 6 cycles. Pre-treatment flow cytometry was performed to assess surface expression of CD11b, CD62, CD69, CD16, CD32 and CD64 in PMNs or NKcells was performed. Serum or PBMC's were isolated from each patient and used 51 Cr release assays to study rituximab-associated complement mediated cytotoxicity (CMC) or ADCC. To correlate laboratory parameters with response rate, and PFS patients were divided in tertiles. Overall, R+LD was very well-tolerated. Overall response rate (ORR) = 68% (39% CR, 19% PR); median time-to-progression (TTP) = 12 m. Surface expression of CD32 in PMNs, and CD69 in NKcells correlated with better response rates. Surface expression of CD11b and CD32 in the PMN's correlated with a longer PFS (P = 0.040 and P = 0.015, respectively).There was a non-statistically significant trend towards an improved in PFS in those patients whom their PBMC's exhibited a higher degree of ex-vivo rituximab ADCC. Our data suggest that R+LD is a safe and effective regimen and that the quality of the immune system prior to a chemo-immunotherapy regimen may play a role in clinical outcomes, specifically the expression of CD11b and CD32 in PMNs or CD69 in NKcells. Our data supports further research in seeking ways to enhance the quality of the immune system to improve responses to rituximab ± chemotherapy. [Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2009.27.15_suppl.8583
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2009
detail.hit.zdb_id:
2005181-5
detail.hit.zdb_id:
604914-X
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