orabase and Multiple-Myeloma

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.. 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.. 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%).. 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.

Topics: Adult; Aged; Antigens, Neoplasm; Cancer Vaccines; Carboxymethylcellulose Sodium; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunization; Immunotherapy, Adoptive; Male; Middle Aged; Multiple Myeloma; Neoplasm Proteins; Poly I-C; Polylysine; T-Lymphocytes; Transplantation, Autologous; Treatment Outcome

Seven patients with refractory multiple myeloma (readily evaluable for response) were treated in a Phase II trial with poly(I,C)-LC using a 3 times per week intravenous schedule. Serial immunologic testing included assessment of natural killer (NK) cell activity, antibody-dependent cytotoxicity, delayed hypersensitivity, and in vitro mitogen responses. One patient had a partial response (PR) of 6-month duration, and 3 other patients had objective responses (less than PR). Significant interferon induction occurred, but levels dropped substantially with serial dosing. Major toxicity included hypertension, hypotension, fever, and myelosuppression. The demonstration of modulation of myeloma progression in this refractory population was encouraging.

Topics: Adult; Aged; Carboxymethylcellulose Sodium; Drug Evaluation; Female; Humans; Interferon Inducers; Male; Methylcellulose; Middle Aged; Multiple Myeloma; Poly I-C; Polylysine; Waldenstrom Macroglobulinemia

Topics: Adult; Aged; Agranulocytosis; Carboxymethylcellulose Sodium; Female; Humans; Indomethacin; Interferons; Lymphopenia; Male; Middle Aged; Multiple Myeloma; Poly I-C; Polylysine