Is a Vaccine for Multiple Myeloma Feasible?

A study presented at the American Association of Cancer Research (AACR) 2021 Annual Meeting found a personalized genomic cancer vaccine was feasible and well-tolerated in a phase 1 trial of patients with cancer, including multiple myeloma (MM).

“While cancer immunotherapy has revolutionized the treatment of cancer, we know that the majority of patients fail to achieve significant clinical response,” said co-author Thomas Marron, MD, PhD, assistant professor at Mount Sinai Health System, via press release. “One reason for this may be due to lack of pre-existing primed T cell response needed for PD-1 blockade to have a significant effect. To address this, personalized neoantigen vaccines may help prime an improved immune response against tumor cells.”

The novel vaccine, PGV-001, was tested in a trial of thirteen patients. Ten patients with solid tumors had undergone curative-intent surgery, and three patients with MM had undergone autologous hematopoietic cell transplantation. Patients were selected who had a >30% chance of disease recurrence.

“Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have less cancer spread,” said co-author Nina Bhardwaj, MD, PhD, Director of the Immunotherapy Program at The Tisch Cancer Institute at Mount Sinai. “We have therefore developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, such as surgery in solid tumors and bone marrow transplant in MM, when patients have minimal–typically microscopic–residual disease.”

Trial participants underwent tumor and germline sequencing and neoantigen peptide synthesis via the OpenVax custom computation pipeline, developed at Mount Sinai. A maximum of 10 peptides were created per patient. These peptides, fused with poly-ICLC and a tetanus helper peptide, were then administered over 27-weeks.

Overall, 11 patients received all 10 doses. One patient stopped treatment at disease progression and another patient died while on treatment. Among the remaining patients, the vaccine was well tolerated. Injection site reactions occurred in 31% of patients.

The median progression-free survival from time of surgery or AHCT of the 12 surviving patients was 20.3 months.  As of a mean 30.4 months follow-up, 4 patients have not had subsequent therapy or evidence of disease, 4 received subsequent therapy, and 4 have died, though only 2 of the deceased patients experienced disease recurrence. Patient samples shows robust T cell reactivity among patients who received all 10 doses.

In conclusion, the researchers wrote: “PGV-001 was successfully synthesized for 15 patients and administered successfully to 13 patients without significant adverse events. Immune monitoring of immunogenicity is ongoing, with initial analysis demonstrating induction of neoantigen-specific CD4 and CD8 T cell expansion.”