“This involves utilizing a personalized vaccine to prevent premalignant conditions from transforming to frank disease,” said Dr Patel. “Such an approach can lead to personalized vaccination of patients with higher-risk MGUS before it becomes myeloma or leads to kidney issues or bone marrow issues.”

He continued, “With vaccination strategies in metastatic tumors, historically efficacy has been limited as often the cat is out of the bag. It is like getting vaccinated when you have the flu already. We need to think about some of these personalized vaccination strategies before the person develops the more advanced cancer, and this work has important clinical and translational implications for the future of personalized vaccination strategies.”

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Dr Patel said the approach used in the current study is similar to what is being tried in solid tumor types in clinical trials; however, the current study findings advance what the recurrent targets are in myeloma. “It is very likely that [this approach] will lead to improved personalized vaccines, and it is hugely important work,” he told Hematology Advisor. “In particular, the clinical outcome data for this version of the vaccine as well as future versions will be informative for this kind of personalized approach. If something is really transformative, it could be available in a couple of years, though at the current time, this approach is experimental and should only be considered in the context of a clinical trial.”

Dr Parekh said he is optimistic that this approach will be successful in this patient population based on the success demonstrated in other tumor types, as “clinical trials with neoantigen peptide vaccines are in more advanced testing for a variety of solid tumors, and there are already preliminary results indicating success.”2,3


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One such vaccine is Personalized Genomic Vaccine 001 (PGV001), a peptide vaccine for MM in patients with advanced nonhematologic malignancies that is based on a patient’s own tumor sequence. “We have just completed accrual to a phase 1 trial of neoantigen vaccines for myeloma patients (ClinicalTrials.gov Identifier: NCT02721043) and are in the process of planning the next trial,” said Dr Parekh. “The current trial is in newly diagnosed patients after autologous transplantation. Our next trial will be for smoldering myeloma.”

The phase 1 trial aims to examine the safety, tolerability, and immunogenicity of PGV001. Each patient’s tumor will be sequenced, and peptides that correspond to the tumors will be developed. The vaccine will combine these peptides with the adjuvant Poly-ICLC (Hiltonol®, Oncovir) in order to boost immune response to the peptides. The researchers hope the 2 components will expand immune cells to target the cancer.

References

1.     Perumal D, Imai N, Laganà A, et al. Mutation-derived neoantigen-specific T-cell responses in multiple myeloma [published online December 19, 2019]. Clin Cancer Res. doi:10.1158/1078-0432.CCR-19-2309

2.     Saxena M, Bhardwaj N. Re-emergence of dendritic cell vaccines for cancer treatment. Trends Cancer. 2018;4:119-137.

3.     Blazquez AB, Rubinsteyn A, Kodysh J, et al. A phase I study of the safety and immunogenicity of a multipeptide personalized genomic vaccine in the adjuvant treatment of solid cancers. Presented at: Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; September 30-October 3, 2018; New York, NY. Abstract A005.