Phase II clinical trial of intratumoral application of TG1042 (adenovirus-interferon-gamma) in patients with advanced cutaneous T-cell lymphomas and multilesional cutaneous B-cell lymphomas.
Cutaneous lymphomas (CLs) are a heterogeneous group of lymphoproliferative disorders that are manageable by immunotherapy. Twenty-one patients were enrolled in a prospective open-label, dose-escalation multicenter study evaluating the effects of repeated TG1042 [adenovirus-interferon (IFN)-gamma] intralesional injections in patients with primary CLs, of which 18 were of T-cell and 3 of B-cell type. Repeated intralesional therapy using TG1042 consistently results in local tumor regressions in about half of treated patients and one-third of patients also in regressions in noninjected distant lesions, likely reflecting the systemic immune activation after intralesional therapy. Treatment was well tolerated with few adverse events including injection site reactions, chills, lymphopenia, and fever. Immune monitoring in the peripheral blood demonstrated systemic immune activation and the induction of antibodies against tumor antigens in some patients without clear association with clinical responses. CLs, in particular B-cell lymphomas with high objective response rates, seem to be excellent targets for this type of immunotherapy.
Dummer
Reinhard
R
Department of Dermatology, University Hospital, Zurich, Switzerland. reinhard.dummer@usz.ch
Eichmüller
Stefan
S
Gellrich
Sylke
S
Assaf
Chalid
C
Dreno
Brigitte
B
Schiller
Meinhard
M
Dereure
Olivier
O
Baudard
Marion
M
Bagot
Martine
M
Khammari
Amir
A
Bleuzen
Pascal
P
Bataille
Vincent
V
Derbij
Anna
A
Wiedemann
Nicole
N
Waterboer
Tim
T
Lusky
Monika
M
Acres
Bruce
B
Urosevic-Maiwald
Mirjana
M
D000256:Adenoviridae / Q000235:genetics*; D006801:Humans; D015552:Injections, Intralesional; D007371:Interferon-gamma / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D016399:Lymphoma, T-Cell / Q000188:drug therapy*; D012878:Skin Neoplasms / Q000628:therapy*
D007371:Interferon-gamma