Phase II trial of idiotype vaccination in previously treated patients with indolent non-Hodgkin's lymphoma resulting in durable clinical responses.
OBJECTIVE
To evaluate idiotype (Id) vaccination as a single agent in previously treated patients with indolent non-Hodgkin's lymphoma.


METHODS
Patients underwent biopsy for determination of their lymphoma-specific Id sequence. Recombinant Id protein was manufactured and covalently linked with keyhole limpet hemocyanin (KLH) to generate Id/KLH. Patients received Id/KLH 1 mg on day 1 subcutaneously, with granulocyte-macrophage colony-stimulating factor 250 mug on days 1 to 4, monthly for 6 months. Booster injections were administered until progression. Both clinical and immune responses were evaluated.


RESULTS
Thirty-two previously treated patients received at least one injection of Id/KLH, and 31 were assessed for efficacy. Responses were observed in four patients (one complete response and three partial responses). Median time to onset of response was 5.9 months (range, 2.3 to 14.1 months). Median duration of response has not been reached but should be at least 19.4 months (range, 10.4 to 27.2+ months). Median time to progression is 13.5 months. The most common adverse events were mild to moderate injection site reactions. Six (67%) of nine patients tested demonstrated a cellular immune response, and four (20%) of 20 patients demonstrated an antibody response against their Id.


CONCLUSIONS
This trial demonstrates that Id/KLH alone can induce tumor regression and durable objective responses. Further study of Id/KLH is recommended in other settings where efficacy may be further enhanced as in first-line therapy or after cytoreductive therapy.
Redfern
Charles H
CH
Sharp Healthcare, San Diego, CA, USA.
Guthrie
Troy H
TH
Bessudo
Alberto
A
Densmore
John J
JJ
Holman
Peter R
PR
Janakiraman
Nalini
N
Leonard
John P
JP
Levy
Richard L
RL
Just
Richard G
RG
Smith
Mitchell R
MR
Rosenfelt
Fred P
FP
Wiernik
Peter H
PH
Carter
William D
WD
Gold
Daniel P
DP
Melink
Teresa J
TJ
Gutheil
John C
JC
Bender
John F
JF
D000328:Adult; D000368:Aged; D000917:Antibody Formation; D019496:Cancer Vaccines; D005260:Female; D006433:Hemocyanins; D006801:Humans; D007111:Immunity, Cellular; D007130:Immunoglobulin Idiotypes / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D019496:Cancer Vaccines; D007130:Immunoglobulin Idiotypes; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin