Re-induction using whole cell melanoma vaccine genetically modified to melanoma stem cells-like beyond recurrence extends long term survival of high risk resected patients - updated results. Issue 1 (29th November 2018)

• Record Type: Journal Article
• Authors: Mackiewicz, Jacek; Burzykowski, Tomasz; Iżycki, Dariusz; Mackiewicz, Andrzej
• Is Part Of: Journal for immunotherapy of cancer. Volume 6:Issue 1(2018)
• Publication Date: 2018-11-29
• Subjects: Melanoma -- Immunotherapy -- Genetic melanoma vaccine -- Long-term survivals -- Phase II clinical trials -- Re-induction; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1186/s40425-018-0456-1
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : Background: AGI-101H is an allogeneic gene modified whole cell therapeutic melanoma vaccine, evaluated in over 400 melanoma patients in the adjuvant and therapeutic settings. We present updated long-term survival results from two single-arm, phase II adjuvant trials (Trial 3 and Trial 5) with the focus on treatment beyond recurrence of the disease. Methods: Patients with resected high-risk melanoma (stage IIIB-IV) were enrolled to Trial 3 ( n = 99) and Trial 5 ( n = 97). The primary endpoint was disease-free survival (DFS), and the secondary was overall survival (OS). In the induction phase, the vaccine was administered every 2 weeks (eight times), followed by the maintenance phase every month until progression. At progression, maintenance was continued or re-induction was applied with or without surgery. Results: In Trial 3, the 10-year DFS was equal to 33.0% overall and to 52.4, 25.0, and 8.7% for stage IIIB, IIIC, and stage IV patients, respectively. In Trial 5, the overall 10-year DFS was equal to 24.2%, and to 37.5, 18.0, and 17.6% for stage IIIB, IIIC, and stage IV patients, respectively. In Trial 3, the 10-year OS was equal to 42.3% overall, and to 59.5, 37.5, and 17.4% for stage IIIB, IIIC, and stage IV patients, respectively. In Trial 5, the 10-year OS was equal to 34.3% overall and to 46.9, 28.0, and 29.4% for stage IIIB, IIIC, and stage IV patients, respectively. Among the 65 patients of Trial 3 who developed progression, 43 received re-induction with ( n = 22) or without ( n = 21) surgery. Two patients received surgery without re-induction. All the 22 progressing patients, who did not receive re-induction, died. Among the 75 patients of Trial 5 who experienced progression, 39 received re-induction with ( n = 21) or without ( n = 18) surgery. Among the 36 progressing patients who did not receive the re-induction, 35 died. Surgery and re-induction reduced (independently) the increase of mortality after progression in both trials, with the effect of re-induction reaching statistical significance in Trial 5. Conclusions: Vaccination beyond recurrence of the disease with additional re-induction combined with surgery or alone increased long term survival of melanoma patients. However, further studies on larger patient cohorts are required. Trial registration: Central Evidence of Clinical Trials (EudraCT Number 2008–003373-40 )