Therapeutic options for patients (pts) with relapsed/refractory B-NHL and poor bone marrow reserve are limited. Denileukin diftitox (DD), a recombinant fusion protein, which when given at the standard dose, is not myelosuppressive and achieved a response rate of 25% in pts with relapsed/refractory B-NHL (

). We conducted a phase II, open label, multi-site study to evaluate efficacy and tolerability of DD given weekly in pts with relapsed/refractory B-NHL who had diminished bone marrow reserve. This is the first study of DD in NHL to use a dosing regimen other than the standard 18 mcg/kg/day for 5 days repeated every 21 days. Pts were required to have failed to respond or have progressive disease (PD) after ≥2 prior treatment regimens, bi-dimensional disease of at least 4cm2, and mild to moderate cytopenia defined as one or more of the following: ANC ≥1000 but <1500, platelets ≥40,000 but <150,000, and WBC ≥2000 but <4000, or have relapsed after prior stem cell transplantation (SCT). Denileukin diftitox was administered at 18 mcg/kg/day ×3 days followed by 21 mcg/kg weekly. Evaluation of response was performed after 8 wks of treatment, and pts with stable disease or objective response were to receive another 8 weekly infusions. Twenty-two pts enrolled; the median age was 67 yrs (range 45–78), median number of previous treatments was 4 (range 2–9), 12 had prior SCT. There were 14 pts with diffuse large cell lymphoma (DLCL), 5 follicular lymphoma (FL), and 3 small lymphocytic lymphoma (SLL). The median lesion size at entry was 21cm2 (range 10–598cm2). Twenty of 22 pts discontinued therapy prematurely, 14 due to PD, 1 with SD, and 5 due to toxicity. The median number of weekly doses given was 4 (range 1–16). No objective responses have been observed to date and enrollment has been suspended. Fourteen pts are alive (10 DLCL, 3 FL, 1 SLL) ranging from 2–14 months from entry. Adverse events observed with weekly dosing were similar to those seen with the standard regimen; however, incidence of most common grade 3–4 toxicities was less, with fatigue 24%, transaminase elevation 18%, and hypoalbuminemia 12%. Although all pts had mild to moderate cytopenia at enrollment, only 2 pts (9%) experienced grade 3–4 neutropenia, none with neutropenic infection, and 1 pt had worsening of thrombocytopenia from grade 3 at study entry to grade 4. In conclusion, weekly dosing of DD is well tolerated, even in pts with diminished marrow reserve, but has not demonstrated significant anti-tumor activity in this heavily pretreated B-NHL population with bulky disease. Follow-up will continue for survival analysis.

Disclosures: The study of ONTAK in the treatment of B-cell lymphoma patients with limited bone marrow reserve.; Mark Acosta employed at Ligand Pharmaceuticals.; Mark Acosta has stock options but currently does not own any stock.; M. Czuczman: Clinical research funding.; Lauren Pinter-Brown has spoken/presented on behalf of Ligand.

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