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Phase II study of a TLR‐9 agonist (1018 ISS) with rituximab in patients with relapsed or refractory follicular lymphoma
Author(s) -
Friedberg Jonathan W.,
Kelly Jennifer L.,
Neuberg Donna,
Peterson Derick R.,
Kutok Jeffery L.,
Salloum Rabih,
Brenn Thomas,
Fisher David C.,
Ronan Elizabeth,
Dalton Virginia,
Rich Lynn,
Marquis Diana,
Sims Paul,
Rothberg Paul G.,
Liesveld Jane,
Fisher Richard I.,
Coffman Robert,
Mosmann Tim,
Freedman Arnold S.
Publication year - 2009
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2009.07773.x
Subject(s) - follicular lymphoma , medicine , rituximab , lymphoma , immune system , cd8 , antibody dependent cell mediated cytotoxicity , adverse effect , immunology , cd20 , gastroenterology , antibody , monoclonal antibody
Summary Toll‐like receptor‐9 (TLR‐9) agonists have pleotropic effects on both the innate and adaptive immune systems, including increased antigen expression, enhanced antibody‐dependent cell‐mediated cytotoxicity (ADCC) and T helper cell type 1 shift in the immune response. We combined a TLR‐9 agonist (1018 ISS, 0·2 mg/kg sc weekly × 4 beginning day 8) with standard rituximab (375 mg/m 2 weekly × 4) in patients ( n = 23) with relapsed/refractory, histologically confirmed follicular lymphoma, and evaluated immunological changes following the combination. Treatment was well‐tolerated with no significant adverse events attributable to therapy. Clinical responses were observed in 48% of patients; the overall median progression‐free survival was 9 months. Biologically relevant increases in ADCC and circulating CD‐3 positive T cells were observed in 35% and 39% of patients, respectively. Forty‐five percent of patients had increased T cells and dendritic cells in skin biopsies of 1018 ISS injection sites 24 h post‐therapy. Pre‐ and post‐biopsies of tumour tissue demonstrated an infiltration of CD8 + T cells and macrophages following treatment. This group of patients had favourable clinical outcome despite adverse prognostic factors. This study is the first to histologically confirm perturbation of the local immune microenvironment following systemic biological therapy of follicular lymphoma.