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Oncolytic Virotherapy Leads to Durable Disease Remissions in R/R T-Cell Lymphoma

lymphoma

A single intravenous infusion of vesicular stomatitis virus interferon-β with sodium iodide symporter resulted in “durable disease remissions in heavily pretreated” patients with relapsed or refractory (R/R) T-cell lymphoma, according to investigators of a phase I clinical trial.

Joselle Cook, MBBS, Kah-Whye Peng, PhD, of Mayo Clinic, and colleagues conducted the trial and published the results in Blood Advances.

The single-center trial included adults with R/R multiple myeloma (n=7), T-cell lymphoma (n=7), or acute myeloid leukemia (n=1). The median age was 64 years. Most patients (60%) were male. The median number of prior systemic cancer therapies was five. Investigators aimed to assess the maximum tolerated dose of vesicular stomatitis virus interferon-β with sodium iodide symporter in these patients, determine its safety profile, and estimate the clinical response rates.

The four doses tested were dose level one, 5 × 109 50% tissue culture infectious dose (TCD50) (n=3); dose level two, 1.7 × 1010 TCD50 (n=3); dose level three, 5 × 1010 TCD50 (n=3); and dose level four, 1.7 × 1011 TCD50 (n=6). Doses were administered by intravenous infusion.

 

No dose-limiting toxicities were reported at any dose level. There were three objective responses to the treatment, all in patients who had T-cell lymphoma, including a three-month partial response at dose level two, a six-month partial response at dose level four, and a complete response ongoing at 20 months at dose level four. Five of the seven patients with T-cell lymphoma had “mixed responses with regression of one or more tumors,” the authors reported.

The treatment “demonstrates compelling dose-dependent efficacy among patients with advanced treatment-refractory” T-cell lymphoma, the authors reported.

The investigators are currently enrolling an expansion cohort of patients with relapsed/refractory peripheral T-cell lymphoma to be treated at dose level four. Researchers are also adding more arms to the phase I trial to evaluate the treatment in combination with drugs that modulate antiviral or antitumor immune response.

Cook J, Peng KW, Witzig TE, et al. Clinical activity of single-dose systemic oncolytic VSV virotherapy in patients with relapsed refractory T-cell lymphoma. Blood Adv. 2022;6(11):3268-3279. doi:10.1182/bloodadvances.2021006631

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