Abstract

Background: Studies of Id/KLH immunotherapy in treatment naïve (TN) fNHL pts following first remission from chemotherapy have demonstrated a prolonged duration of remission. We expanded this approach in a PhII trial to include TN and relapsed/refractory (R/R) pts with stable disease (SD) or PR or CR/CRu following 4 wkly doses of rituximab. We report here long term follow up of RRI, defined as the % of pts who converted from SD to PR or PR to CR/CRu following initiation of Id/KLH treatment, and analysis of disease progression.

Treatment: Pts received rituximab (375mg/m2 i.v. wkly x 4 during wk1–4) and those with stable or responsive disease received Id/KLH (1 mg s.q. mo x 6) starting on wk 12 along with GM-CSF (250 mcg, s.q.) on days 1–4. Pts continued to receive booster injections on a reduced schedule until disease progression. Radiological scans, performed every 3 mos, were reviewed centrally. Disease progression and response were assessed using modified Cheson criteria. This data analysis was performed 32 mo from end of enrollment.

Results: 103 pts were enrolled and received rituximab; 89 pts had ≥SD and received Id/KLH + GM-CSF of whom, 54 were R/R, and 35 were TN. The overall response rate (ORR) was 47% (42/89) at mo 3. After the initiation of Id/KLH dosing, ORR improved to 63% (56/89). In RRI pts, median time to best response was 9.1 mos from start of rituximab treatment (5.2 – 29.6 mos). 12 of 39 PR pts (31%) converted to CR/Cru. 14 of 43 SD pts (33%) converted to PR.

Pt Groups# of Pts% Prog FreeMedian TTP Est by K-M (mo)
Pts w/RRI 26 69% 37.9 
TN rituximab responders 23 70% Not Reached (NR) 
Rituximab responders (All) 42 60% NR 
Non Responders (All) 47 36% 14.9 
All Pts 89 47% 18.2 
TN Pts (All) 35 66% NR 
Relapsed Pts (All) 54 37% 16.8 
Pt Groups# of Pts% Prog FreeMedian TTP Est by K-M (mo)
Pts w/RRI 26 69% 37.9 
TN rituximab responders 23 70% Not Reached (NR) 
Rituximab responders (All) 42 60% NR 
Non Responders (All) 47 36% 14.9 
All Pts 89 47% 18.2 
TN Pts (All) 35 66% NR 
Relapsed Pts (All) 54 37% 16.8 

Conclusion: RRI following FavId is seen in nearly one third of pts. The magnitude of this improvement, the number of conversions to CR/CRu and median time to best response (9 mo and as late as 29.6 mo) suggests this is likely to be a FavId effect rather than late response to rituximab. Responders and TN pts show more durable responses compared to previously published data for rituximab therapy. FavId may also confer a benefit for nonresponders and R/R pts relative to rituximab alone. To confirm benefit of FavId following rituximab induction, a placebo controlled PhIII study was initiated; it completed enrollment in Jan 06. RRI data from this study is expected to be available in Nov 06.

Disclosure: No relevant conflicts of interest to declare.

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