The measles virus was evaluated in a phase 1/2 trial of patients with recurrent or refractory MM.2 Patients received the virus ― MV-NIS, which expressed thyroidal sodium iodide symporter ― only during stage 1 of the trial, or were pretreated with cyclophosphamide in stage 2. Dramatic results of 2 of the patients treated with measles virus were published in 2014. Both patients were treated with the highest dose level of the virus and did not have detectable antimeasles antibodies. Tumor-targeted infection — without spread to adjacent normal tissue ― was demonstrated with radioiodine uptake of the lesions in SPECT-CT scans.
Both patients experienced a response, but 1 patient “remains in complete remission 4 years post measles virus therapy and is the posterchild for what can be achieved with a single infusion of an oncolytic virus,” Dr Russell said.
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Adverse effects included fever, severe headache, tachycardia, and hypotension during the initial hours after infusion.
Dr Russell noted that although some anticancer activity has been observed in subsequent patients, this dramatic response has not been replicated.
“We are trying to understand what factors determine treatment success and we think we have made considerable headway,” Dr Russell said. “The trials are continuing with emphasis on a subset of myeloma patients who have not been too heavily pretreated and who still have a strong immune system.”
Future Directions
Several trials are ongoing with different viruses or combination therapy. “We are planning clinical trials using cellular carriers as Trojan Horses to more efficiently deliver the virus to sites of myeloma growth, which is especially important for patients who have antimeasles antibodies from childhood vaccination or infection,” Dr Russell explained.
A new trial was opened in April 2017 with the vesicular stomatitis virus (ClinicalTrials.gov Identifier: NCT03017820), which demonstrated greater success in the lab, according to Dr Russell.
“Better understanding of the clinical performance of existing viruses, continued clinical trials to determine how to use these agents for myeloma therapy, and a stronger commercial emphasis to further accelerate their development,” concluded Dr Russell.
References
- Oliva S, Gambella M, Boccadoro M, Bringhen S. Systemic virotherapy for multiple myeloma. Expert Opin Biol Ther. 2017 Aug 10. [Epub ahead of print] doi: 10.1080/147125598.2017.1364359
- Russell SJ, Federspiel MJ, Peng KW, et al. Remission of disseminated cancer after systemic oncolytic virotherapy. Mayo Clin Proc. 2014;89(7):926-933. doi: 10.1016/j.mayocp.2014.04.003
