In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 8016-8016
Abstract:
8016 Background: Host T-cells mount immune responses (IR’s) against Wilms tumor 1 (WT1) in A*0201 + MM pts through formation of WT1 peptide fragment (RMFPNAPYL)/HLA-A*0201 complex. We report initial results from MM pts immunized with the WT1 heteroclitic peptide mixture galinpepimut-S (GPS) after autoSCT. Methods: 16 MM pts underwent autoSCT with melphalan conditioning followed by (f/b) lenalidomide maintenance starting 3 months (mos) post-SCT. 13/16 pts presented with high-risk (HR) cytogenetics [t(4;14), t(14;16), del17p, 1q21/25 gain and/or del13q]. GPS was administered with montanide s.c. starting 2 wks post-SCT and q.2 wks thereafter x 6 initial doses f/b boosters q.4 wks x 6 additional doses. GM-CSF was given on days -2 and 0 of each cycle. GPS consisted of 4 peptides: WT1-A1: Y*MFPNAPYL; 427-L (long): RSDELVRHHNMHQRNMTKL; 331-L: PGCNKRYFKLSHLQMHSRKHTG, and 122A1-L: SGQAY*MFPNAPYLPSCLES. 2 of the 4 peptides were mutated at a single residue (*) to induce stronger HLA-binding/reduce tolerance. WT1-specific IR’s were assessed by intracellular IFN-g analyses post-challenge with PBMC’s pulsed with a ‘total pool’ of overlapping 15mers along the entire WT1 protein; or each of the 4 WT1 peptides in GPS; or the non-mutated (native) WT1 peptides corresponding to the 2 heteroclitic sequences. Results: 16 pts; median follow-up: 18 mos (range: 5-31 mos) for survivors; median age: 61.6 y. Overall survival (OS) and progression-free survival (PFS) (95% CI) at 18 mos: 0.88 (0.73-0.99) and 0.62 (0.42-0.97) respectively. Current median PFS: 23.6 mos (15.2 - not reached). No 〉 G2 systemic side effects were observed, however, all pts developed local nodularity at the site of injections which resolved over 2 – 6 wks. Both CD8+ and CD4+ IR’s could be detected at various levels and were induced not only against the heteroclitic peptides (within GPS), but also against the corresponding native WT1 peptide sequences as well as the ‘total pool’ of WT1-derived overlapping peptides. Conclusions: Administration of the novel WT1 heteroclitic peptide immunizer GPS post auto SCT demonstrates favorable safety profile along with encouraging mPFS of currently 23.6 mos in this high-risk MM population. Clinical trial information: NCT01827137.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.15_suppl.8016
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
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