Combination immunotherapy after ASCT for multiple myeloma using MAGE-A3/Poly-ICLC immunizations followed by adoptive transfer of vaccine-primed and …
AP Rapoport, NA Aqui, EA Stadtmauer, DT Vogl… - Clinical cancer …, 2014 - AACR
Clinical cancer research, 2014•AACR
Purpose: Myeloma-directed cellular immune responses after autologous stem cell
transplantation (ASCT) may reduce relapse rates. We studied whether coinjecting the TLR-3
agonist and vaccine adjuvant Poly-ICLC with a MAGE-A3 peptide vaccine was safe and
would elicit a high frequency of vaccine-directed immune responses when combined with
vaccine-primed and costimulated autologous T cells. Experimental Design: In a phase II
clinical trial (NCT01245673), we evaluated the safety and activity of ex vivo expanded …
transplantation (ASCT) may reduce relapse rates. We studied whether coinjecting the TLR-3
agonist and vaccine adjuvant Poly-ICLC with a MAGE-A3 peptide vaccine was safe and
would elicit a high frequency of vaccine-directed immune responses when combined with
vaccine-primed and costimulated autologous T cells. Experimental Design: In a phase II
clinical trial (NCT01245673), we evaluated the safety and activity of ex vivo expanded …
Abstract
Purpose: Myeloma-directed cellular immune responses after autologous stem cell transplantation (ASCT) may reduce relapse rates. We studied whether coinjecting the TLR-3 agonist and vaccine adjuvant Poly-ICLC with a MAGE-A3 peptide vaccine was safe and would elicit a high frequency of vaccine-directed immune responses when combined with vaccine-primed and costimulated autologous T cells.
Experimental Design: In a phase II clinical trial (NCT01245673), we evaluated the safety and activity of ex vivo expanded autologous T cells primed in vivo using a MAGE-A3 multipeptide vaccine (compound GL-0817) combined with Poly-ICLC (Hiltonol), granulocyte macrophage colony-stimulating factor (GM-CSF) ± montanide. Twenty-seven patients with active and/or high-risk myeloma received autografts followed by anti-CD3/anti-CD28–costimulated autologous T cells, accompanied by MAGE-A3 peptide immunizations before T-cell collection and five times after ASCT. Immune responses to the vaccine were evaluated by cytokine production (all patients), dextramer binding to CD8+ T cells, and ELISA performed serially after transplant.
Results: T-cell infusions were well tolerated, whereas vaccine injection site reactions occurred in >90% of patients. Two of nine patients who received montanide developed sterile abscesses; however, this did not occur in the 18 patients who did not receive montanide. Dextramer staining demonstrated MAGE-A3–specific CD8 T cells in 7 of 8 evaluable HLA-A2+ patients (88%), whereas vaccine-specific cytokine-producing T cells were generated in 19 of 25 patients (76%). Antibody responses developed in 7 of 9 patients (78%) who received montanide and only weakly in 2 of 18 patients (11%) who did not. The 2-year overall survival was 74% [95% confidence interval (CI), 54%–100%] and 2-year event-free survival was 56% (95% CI, 37%–85%).
Conclusions: A high frequency of vaccine-specific T-cell responses were generated after transplant by combining costimulated autologous T cells with a Poly-ICLC/GM-CSF–primed MAGE-A3 vaccine. Clin Cancer Res; 20(5); 1355–65. ©2013 AACR.
AACR