A phase 2 trial of immunotherapy with mitumprotimut-T (Id-KLH) and GM-CSF following rituximab in follicular B-cell lymphoma.
We evaluated the efficacy and safety of patient-specific immunotherapy with mitumprotimut-T idiotype keyhole limpet hemocyanin and granulocyte-monocyte colony-stimulating factor (GM-CSF) following rituximab in patients with follicular B-cell lymphoma. Patients with previously untreated or relapsed/refractory CD20+ follicular lymphoma received 4 weekly infusions of rituximab and those with a complete response (CR), partial response (PR), or stable disease received mitumprotimut-T and GM-CSF injections subcutaneously. Courses were given monthly for 6 doses, every 2 months for 6 doses, and then every 3 months until disease progression. Computed tomography scans were obtained every 3 to 6 months and reviewed centrally. The primary endpoint was event-free survival (EFS). Among 103 patients treated with rituximab, 92 (54 relapsed/refractory and 38 previously untreated) received mitumprotimut-T/GM-CSF; median age was 53 years, 91% had stage III to IV disease, and 59% had failed earlier therapy. The premitumprotimut-T objective response rate was 47% (2 CRs, 41 PRs). During the mitumprotimut-T treatment phase, 16 patients converted to CR resulting in an overall objective response rate of 60% (18 CRs, 37 PRs). Median EFS was 15.2, 20.8, and 13.5 months for all, treatment-naive, and relapsed/refractory disease patients, respectively. Anti-Id cellular immune responses were detected in 13 of 18 (72%) patients and humoral immune responses in 17 of 83 (20%) patients. Adverse events were usually mild-to-moderate. The most common adverse event was injection site reactions. Mitumprotimut-T/GM-CSF-induced anti-Id cellular immune responses in most patients. The occurrence of late CRs and favorable EFS suggested a clinical benefit of active immunotherapy and led to a placebo-controlled phase 3 trial.
Department of Regional Oncology, Cleveland Clinic, Beachwood, OH 44122, USA. KOCO@ccf.org
Omer N
ON
Koç
Charles
C
Redfern
Peter H
PH
Wiernik
Fred
F
Rosenfelt
Jane N
JN
Winter
William D
WD
Carter
Dan P
DP
Gold
Morgan E
ME
Stewart
Richard G
RG
Ghalie
John F
JF
Bender
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000096:biosynthesis / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D018572:Disease-Free Survival; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006433:Hemocyanins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects; D007130:Immunoglobulin Idiotypes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007167:Immunotherapy; D007279:Injections, Subcutaneous; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008224:Lymphoma, Follicular / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D011994:Recombinant Proteins; D000069283:Rituximab
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000951:Antigens, Neoplasm; D007130:Immunoglobulin Idiotypes; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D000069283:Rituximab; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin