Waldenstroms Macroglobulinemia

Waldenstrom's macroglobulinemia (WM) is an uncommon lymphoid malignancy characterized by IgM monoclonal gammopathy and intertrabecular marrow infiltration by small lymphocytes expressing CD20 antigen. Currently, rituximab can be used for the treatment of WM with response rates between 20% and 50% (62,63).

The impact of FCGR3A polymorphism on the response to rituximab for WM has been demonstrated by the work of Treon et al. (Table 3) (64). They reported that two polymorphisms, FCGR3A-43 and FCGR3A-158, correlate with response to rituximab therapy (375 mg/m2 weekly infusion), but not with time to progression (TTP) or progression-free survival (PFS).

The response rate after rituximab therapy was significantly different in favor of the VV genotype of FCGR3A-158 polymorphism as follows: 40% in VV, 35% in VF, and 9% in FF genotype groups (p = 0.03). In addition, the response rate was also in favor of the LR or LH genotype of FCGR3A-48 polymorphism as follows: 38.5% in LH, 25% in LR, and 22% in LL genotype groups (p = 0.057). However, no significant difference in PFS or TTP was observed according to the FCGR3A-48 or FCGR3A-158 polymorphisms. To reach clear conclusion on the issue of whether the Fc^ receptor gene polymorphism influences on treatment outcome of rituximab therapy for WM, further studies with larger number of patients are warranted.

Table 3

The Influence of Single Nucleotide Polymorphism on the Treatment Outcomes for Other Lymphoid Malignancies Besides Follicular

Lymphoma

Reference (year)

Treatment Modality

Polymorphism Outcomes

Significances References to to o

Diffuse large B-cell lymphoma

Chronic lymphocytic leukemia

Farag (2004) Rituximab in untreated or pretreated CLL (n = 30) Lin (2005) Alemtuzumab in relapsed

CLL (n = 36) Waldenstrom's macroglobulinemia Treon (2005) Rituximab in untreated or pretreated WM (n = 58)

FCGR3A-158 FCGR3A-158

FCGR2A-131

FCGR3A-158

FCGR2A-131 FCGR3A-158 FCGR2A-131

FCGR3A-158

FCGR3A-48

PFS, TTP, no difference Response, LH (38.5%), LR (25%), LL (22%) PFS, TTP, no difference

61 61

Fig. 4. Response to frontline R-CHOP therapy for diffuse large B-cell lymphoma patients according toFCGR3A-158 andFCGR2A-131 polymorphisms. A higher rate of complete response was observed in the group with VV genotype (88%) compared to those with the VF (79%) or FF genotype (50%) for FCGR3A (p = 0.002). The difference in overall response rate was also significant favoring the patients with the VV genotype for FCGR3A (98%) versus those with the VF (90%) or FF genotype (50%;p < 0.001). B. According to the FCGR2A-131 polymorphism, however, a significant difference in response rate was not observed. The overall response rate of patients with the HH, HR, and RR genotype was 95%, 92%, and 75%, respectively (p = 0.137). (Originally published in Blood. Kim DH, Jung HD, Kim JG et al, eds. FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy for diffuse large B-cell lymphoma. Blood, 2006; 108(8): 2720-2725. © Copyright American Society of Hematology).

Fig. 4. Response to frontline R-CHOP therapy for diffuse large B-cell lymphoma patients according toFCGR3A-158 andFCGR2A-131 polymorphisms. A higher rate of complete response was observed in the group with VV genotype (88%) compared to those with the VF (79%) or FF genotype (50%) for FCGR3A (p = 0.002). The difference in overall response rate was also significant favoring the patients with the VV genotype for FCGR3A (98%) versus those with the VF (90%) or FF genotype (50%;p < 0.001). B. According to the FCGR2A-131 polymorphism, however, a significant difference in response rate was not observed. The overall response rate of patients with the HH, HR, and RR genotype was 95%, 92%, and 75%, respectively (p = 0.137). (Originally published in Blood. Kim DH, Jung HD, Kim JG et al, eds. FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy for diffuse large B-cell lymphoma. Blood, 2006; 108(8): 2720-2725. © Copyright American Society of Hematology).

Fig. 5. The cumulative incidence of complete response to frontline R-CHOP therapy for diffuse large B-cell lymphoma according to the FCGR3A polymorphism. The time to achieve a complete response after R-CHOP was shorter in the group with the VV genotype (median 70 days, 95% C.I. [52-88 days]) compared to those with the VF or FF genotype for FCGR3A-158 (median, 99 days, 95% C.I. [60-138days]; p = 0.020 by Wilcoxon test). This research was originally published in Blood. Kim DH, Jung HD, Kim JG et al. FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy for diffuse large B-cell lymphoma. Blood, 2006; 108(8): 2720-2725. © Copyright American Society of Hematology.

Fig. 5. The cumulative incidence of complete response to frontline R-CHOP therapy for diffuse large B-cell lymphoma according to the FCGR3A polymorphism. The time to achieve a complete response after R-CHOP was shorter in the group with the VV genotype (median 70 days, 95% C.I. [52-88 days]) compared to those with the VF or FF genotype for FCGR3A-158 (median, 99 days, 95% C.I. [60-138days]; p = 0.020 by Wilcoxon test). This research was originally published in Blood. Kim DH, Jung HD, Kim JG et al. FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy for diffuse large B-cell lymphoma. Blood, 2006; 108(8): 2720-2725. © Copyright American Society of Hematology.

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