The response to the anti-CD20 antibody Rituximab used as a single agent in follicular lymphoma (FL) patients can be predicted by the valine/phenylalanine (V/F) dimorphism of amino acid 158 of Fcγ Receptor IIIA (Fcγ RIIIA) (

Cartron et al.,
Blood
99
:
754
,
2002
;
Weng and Levy,
JCO
21
:
3940
,
2003
). This suggested important contributions for Fcγ RIIIA mediated mechanisms like antibody dependent cellular cytotoxicity to the efficacy of the antibody. Recently, the German Low Grade Lymphoma Study Group (GLSG) demonstrated a significant shorter time to treatment failure (TTF) in patients who received standard CHOP (cyclophosphamide d1, doxorubicin d1, vincristin d1, prednisone d1-5) chemotherapy only compared to patients who received Rituximab (d1) plus CHOP (R-CHOP). Estimated median TTF was 2.6 years in FL patients treated with CHOP and was not reached after 3 years observation time in R-CHOP treated FL patients (p<0.0007) (Blood 102, Abstract # 352, 2003). We examined the Fcγ RIIIA dimorphism in 75 FL patients from this GLSG trial who were treated with 6 to 8 cycles R-CHOP followed by interferon maintenance or high dose chemo-radiotherapy and autologous stem cell transplantation. Using a TaqMan assay with allele specific fluorochrome labelled probes we detected a V/V genotype in 8 patients (10.7%), a V/F genotype in 38 patients (50.6%), and an F/F genotype in 29 patients (38.7%). Patients with different Fcγ RIIIA status responded similarly to R-CHOP (CR rate: V/V 37.5%, V/F 36.8%, F/F 24.1%; overall response rate: V/V 100.0 %, V/F 97.4%, F/F 96.6%; ns). Moreover, TTF was not significantly different between the groups with V/V, V/F, and F/F Fcγ RIIIA(log rank p = 0.48) after a median observation time of 24 months. A correlation between the Fcγ RIIIA status and the efficacy of R-CHOP could not be demonstrated in this large patient cohort. On the other hand it is evident that R-CHOP treated patients significantly benefited from the addition of Rituximab to CHOP chemotherapy in comparison to the standard arm of this randomized trial. This observation supports the hypothesis that the anti-lymphoma effects of Rituximab when used in combination with chemotherapy might be mediated by Fcγ RIIIA-independent mechanisms such as complement dependent cytotoxicity or direct apoptosis induction.

Topics:
cancer immunotherapy, follicular lymphoma, rituximab, r-chop, cyclophosphamide, doxorubicin, prednisone, and vincristine, chemotherapy regimen, antibodies, amino acids, autologous stem cell transplant, cyclophosphamide

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2005, The American Society of Hematology
2004
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