Denileukin diftitox in combination with rituximab for previously untreated follicular B-cell non-Hodgkin's lymphoma.
Follicular lymphoma exhibits intratumoral infiltration by non-malignant T lymphocytes, including CD4+CD25+ regulatory T (T(reg)) cells. We combined denileukin diftitox with rituximab in previously untreated, advanced-stage follicular lymphoma patients anticipating that denileukin diftitox would deplete CD25+ T(reg) cells while rituximab would deplete malignant B cells. Patients received rituximab 375 mg/m(2) weekly for 4 weeks and denileukin diftitox 18 mcg/kg/day for 5 days every 3 weeks for 4 cycles; neither agent was given as maintenance therapy. Between August 2008 and March 2010, 24 patients were enrolled. One patient died before treatment was given and was not included in the analysis. Eleven of 23 patients (48%; 95% confidence interval (CI): 27-69%) responded; 2 (9%) had complete responses and 9 (39%) had partial responses. The progression-free rate at 2 years was 55% (95%CI: 37-82%). Thirteen patients (57%) experienced grade ≥3 adverse events and one patient (4%) died. In correlative studies, soluble CD25 and the number of CD25+ T cells decreased after treatment; however, there was a compensatory increase in IL-15 and IP-10. We conclude that although the addition of denileukin diftitox to rituximab decreased the number of CD25+ T cells, denileukin diftitox contributed to the toxicity of the combination without an improvement in response rate or time to progression.
Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA. ansell.stephen@mayo.edu
S M
SM
Ansell
H
H
Tang
P J
PJ
Kurtin
P A
PA
Koenig
G S
GS
Nowakowski
D A
DA
Nikcevich
G D
GD
Nelson
Z
Z
Yang
D M
DM
Grote
S C
SC
Ziesmer
P T
PT
Silberstein
C
C
Erlichman
T E
TE
Witzig
D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004167:Diphtheria Toxin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D000069283:Rituximab; D013601:T-Lymphocytes / Q000276:immunology
D058846:Antibodies, Monoclonal, Murine-Derived; D004167:Diphtheria Toxin; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox; D000069283:Rituximab