title: Phase II study of denileukin diftitox for previously treated indolent non-Hodgkin lymphoma: final results of E1497.
abstract: Denileukin diftitox (DD) is approved for treatment of CD-25 expressing cutaneous T-cell lymphomas (CTCL). Initial studies of DD demonstrated responses in patients with B-cell non-Hodgkin lymphoma (NHL). This phase II trial evaluated response rate (RR) and tolerability of DD in this population. Patients were stratified into two arms: those with NHL expressing > or =20% IL-2R (IL-2R+) or <20% IL-2R (IL-2R-). DD was dosed at 18 microg/kg/day for 5 days every 21 days. Corticosteroid pre-medication was not allowed. Thirty-five patients of a planned 77 accrued due to closure for slow accrual. This report is on 29 patients (18 males) with indolent B-cell NHL (11 IL-2R+ and 18 IL-2R-). Histologic subtypes included small lymphocytic (SLL) (8 patients) and follicular grade I/II lymphoma (21 patients). Patients received a median of three prior regimens, including rituximab in 76%. Three partial responses were observed (RR 10%). The RR for the IL-2R- and IL-2R+ patients was 11% and 9%, respectively. Of 8 patients with SLL, 2 responded. Toxicities were generally grade I - II and transient but 1 patient experienced a fatal thrombo-embolism. Therapy with DD is tolerable and modest efficacy was observed in SLL subtype. Measured IL-2R status did not correlate with efficacy.
authors.affiliation: Feinberg School of Medicine-Northwestern University, Chicago, IL 60611, USA. t-kuzel@northwestern.edu
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Kuzel
authors.forename: Shuli
authors.initials: S
authors.lastname: Li
authors.forename: John
authors.initials: J
authors.lastname: Eklund
authors.forename: Francine
authors.initials: F
authors.lastname: Foss
authors.forename: Randy
authors.initials: R
authors.lastname: Gascoyne
authors.forename: Neil
authors.initials: N
authors.lastname: Abramson
authors.forename: John F
authors.initials: JF
authors.lastname: Schwerkoske
authors.forename: Edie
authors.initials: E
authors.lastname: Weller
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Horning
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004167:Diphtheria Toxin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox