By comparing the newly diagnosed patients to relapsed patients, the researchers showed that patients who had failed multiple lines of therapy and who would have normally been expected to have a depleted immune system had “a higher tumor mutation burden and neoantigen load and therefore, may be more sensitive to immunotherapy,” said Neeha Zaidi, MD, an assistant professor of oncology at Johns Hopkins School of Medicine in Baltimore, Maryland, who was not involved with the study. “This is something that should be paid attention to in the future in studies that look at the timing of when to use a specific therapy.”
The researchers were able to identify neoantigens specific to each patient’s tumor. They also identified 3 multiple myeloma oncogenic driver mutations (KRAS, NRAS, and IRF4) shared across multiple patients. “This creates the possibility of coming up with an off-the-shelf product, like a peptide vaccine,” that would be less expensive and less labor-intensive to produce, Dr Zaidi said.
Dr Parekh said he is currently working with colleagues at the Icahn School of Medicine at Mount Sinai to develop this type of vaccine. If it’s effective, he said, it could potentially also be used to keep disease progression from occurring in patients with smoldering myeloma.
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Whether it will be possible to study checkpoint inhibitors in multiple myeloma is uncertain. The US Food and Drug Administration (FDA) stopped a pair of phase 3 trials of the PD-L1 inhibitor pembrolizumab (KEYNOTE studies; ClinicalTrials.gov Identifiers: NCT02576977 and NCT02579863) in July 2017 after an interim analysis requested by the FDA showed higher mortality in the patients randomly assigned to receive pembrolizumab along with other anticancer drugs.2,3
“Because of this, companies lost interest,” noted Dr Parekh. “But I think now is the right time to coordinate with the FDA to do new trials” that look at checkpoint inhibitors in patients with multiple myeloma who have tumors that express these neoantigens. “The concept is now supported and we’d be happy to be part of a study that looked into it,” he said.
Disclosure: Some of the authors of the study of interest disclosed financial relationships with medical device and/or pharmaceutical companies. For a full list of disclosures, please refer to the original study.
References
- Perumal D, Imai N, Laganà A, et al. Mutation-derived neoantigen-specific T-cell responses in multiple myeloma. Clin Cancer Res. 2020;26(2):450-464.
- Mateos MV, Blacklock H, Schjesvold F, et al. Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomized, open-label, phase 3 trial. Lancet Haematol. 2019;6(9):e459-e469.
- Usmani SZ, Schjesvold F, Oriol A, et al. Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naive multiple myeloma (KEYNOTE-185): a randomized, open-label, phase 3 trial. Lancet Haematol. 2019;6(9):e448-e458.
