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Inhibiting TNFα with etanercept in relapsed/refractory follicular lymphoma.

17525 Background: Follicular dendritic cells (FDC) support the survival of follicular lymphoma (FL). TNFα is overexpressed by FL cells and TNFα plays a central role in the development and maintenance of normal FDCs. TNFα may be an ideal target for therapy due to its pleotropic effects on FDCs. Inhibition of TNFα is possible with the decoy receptor, etanercept.


METHODS
Patients with relapsed/refractory FL received 8 weeks of etanercept, 25 mg SC on day 1 and 4 of each week. Patients with any response or stable disease (SD) received 16 more weeks of etanercept at the same dose/schedule. 7 patients enrolled from April 2002 to September 2005. Median age was 63. All patients had stage III/IV disease and had received multiple chemotherapy regimens (median 3); 2 had prior autologous stem cell transplant. FDG-PET was performed at baseline and after 8 (scan 1, n = 7 patients) and 24 weeks on therapy (scan 2, n = 3 patients). Maximum standardized uptake values (SUVmax) were measured in up to 3 lesions per patient (n = 17 lesions for scan 1; 7 lesions for scan 2). The summation SUVmax of all lesions was calculated at each time point. The percentage (%) change in SUVmax in individual lesions and the summed SUVmax for each patient was calculated relative to baseline. The % metabolic response (mR) was assessed using EORTC thresholds for % SUVmax change (mPR ≤ -25% < mSD < +25% ≤ PD).


RESULTS
All patients completed at least 8 weeks of etanercept. 2 patients completed 24 weeks. 5 patients had minor or mixed responses. At the 8 week evaluation 5 patients had SD and 2 had progressive disease (PD). Of the 5 with SD, 2 progressed at 9 and 12 weeks of therapy and 3 progressed by 24 weeks. PET scan 1 showed mPR in 5/7 pts, SD in 2/7 and no PD. PET scan 2 showed mPR in 2/3 pts, mSD in 1/3 and no mPD.All patients are alive at a median of 20+ months after therapy. 1 grade 3 toxicity (lymphopenia) and 3 grade 1/2 toxicities (rhinitis/URI and 2 injection site reactions) were reported.


CONCLUSIONS
Etanercept was well tolerated and minor clinical responses were observed. By EORTC criteria for metabolic response, mPR occurred in 5/7 pts, mSD in 2/7 and there was no mPD. The significant number of metabolic PR's suggest that targeting the microenvironment with agents like etanercept may be a novel treatment approach for FL. No significant financial relationships to disclose.