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Microbes & Immunity Factors associated with response to T-VEC

1. Introduction administration of T-VEC for resectable stage IIIB-IVM1a
melanoma compared with surgery alone in a randomized
Despite the increase in the treatment options for patients phase 2 trial.
with malignant melanoma, the most efficacious approach
and treatment sequence for patients with advanced Consequently, the goal of this study was to identify
melanoma are not well defined. Intralesional therapy with covariates associated with the response to T-VEC within
talimogene laherparepvec (T-VEC, commercially available our patient cohort, aiming to provide insights that can
®
as Imlygic ) is a promising locoregional treatment option for enhance future research endeavors concerning patient
unresectable metastatic melanoma. However, the response selection for T-VEC and the strategic integration of T-VEC
rates are variable. 1 into the current therapy plans.
T-VEC is the first injectable herpes simplex virus 2. Methods
type 1 oncolytic virus therapy approved for unresectable
melanoma of the skin, subcutaneous tissue, or lymph nodes 2.1. Patients’ information
and is currently the only United States Food and Drug This retrospective, single-center study was conducted at
Administration (FDA)-approved intralesional therapy. The the University of Vermont Cancer Center (UVMCC) and
OPTiM trial (conducted 2009 – 2011) was a randomized, focused on sequential melanoma patients treated with
open-label, multinational trial involving 436 patients T-VEC. Institutional Review Board approval was obtained
with unresectable stage IIIB-IVM1c melanoma. The trial for this study. Data were extracted from the electronic
demonstrated a significant improvement in the durable medical records spanning from 2018, when T-VEC
response rate, with patients achieving either a complete or became available on formulary, through 2022. Inclusion
2
partial response for at least 6 months. The OPTiM trial criteria comprised patients aged ≥18 years diagnosed with
established the safety and efficacy of T-VEC in clinical metastatic melanoma and receiving T-VEC treatment
practice, leading to FDA approval of the injection in 2015. 2,3 exclusively at UVMCC, excluding cases treated at an
Recent studies have evaluated the combination of external institution. Patients with a history of or concurrent
T-VEC plus immune checkpoint inhibitors (ICI). While use of targeted therapy or ICI, including PD-1 inhibitors and
the combination with ipilimumab demonstrated evidence CTLA-4 antibody inhibitors, were not excluded from the
of improved objective response rate compared to historic study. Recorded patient variables included demographic,
cohorts of either agent as monotherapy, a randomized clinical, and pathological data, as well as the stage at initial
1
trial assessing pembrolizumab in combination with presentation and at the commencement of T-VEC therapy,
T-VEC failed to demonstrate significant improvement along with the somatic mutation status of the tumor, which
over pembrolizumab alone, despite promising results focused on BRAF and NRAS mutations. Details of the
4
in the phase 1 setting. Carr et al. concluded that while T-VEC treatment course, including injection site, lesion
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6
sequential or concurrent use of T-VEC with ICI did not type (skin, subcutaneous, nodal), number of treatment
significantly affect in-field response, T-VEC demonstrated cycles, and treatment duration, were documented. In
efficacy after failure of ICI. The efficacy of T-VEC following addition, prior and concurrent cancer-directed treatments
progression on a prior PD-1 inhibitor is also supported by were recorded, with particular attention to systemic
preliminary data from the SWOG S1607 study assessing the therapies and immunotherapies. Finally, clinical outcomes
combination of T-VEC and pembrolizumab for melanoma were collected for analysis.
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patients who had experienced progression. Thus,
predictors of response to T-VEC injections in patients with 2.2. Data collection
advanced melanoma and how to best integrate T-VEC into We recorded demographic data, including age,
a treatment plan are still an active area of investigation. race/ethnicity, and gender, alongside clinical and
Multiple patient and disease characteristics have been pathological characteristics such as the year of initial
associated with an improved response to T-VEC and diagnosis, BRAF and NRAS mutation status, Breslow
could aid in patient selection. A lower disease burden, depth, presence of ulceration, and stage at diagnosis.
initiation as an earlier line of therapy, and longer duration Disease burden at T-VEC initiation was defined as
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of treatment have all been correlated with a better low (<5 lesions and/or <5 cm total diameter) or high
response to T-VEC. In addition, T-VEC might be a (≥5 lesions and/or total diameter of lesion ≥5 cm), based on
6,9
preferable choice for older patients who are not suitable established criteria adjusted according to the distribution
candidates for systemic therapies due to the potential side of disease burden within our cohort. Recorded treatment
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effects. Dummer et al. demonstrated a promising 25% details included the date of treatment initiation, number
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reduction in the risk of disease recurrence for neoadjuvant of T-VEC cycles, prior therapy modalities, use and timing
Volume 1 Issue 1 (2024) 96 doi: 10.36922/mi.3445