Page 103 - MI-1-1

Microbes & Immunity Factors associated with response to T-VEC

of ICI (prior or concurrent), lines of systemic therapy, and 2.4. Statistical analysis
clinical outcomes. To evaluate covariates associated with ORR
The primary outcome measured was the in-field overall (partial + complete) as well as our subset analysis
response rate (ORR: complete + partial). The response focusing on the complete in-field treatment response,
to T-VEC was determined by a decrease in size and/or we used two-sample t-tests for continuous variables and
number of lesions. Secondary outcomes included complete Fisher’s exact test for categorical variables. Our secondary
ORR, defined as complete resolution of disease or negative endpoints, DFFS and OS, underwent similar analyses
biopsy. Additional secondary outcomes included disease using two-sample t-tests for continuous variables and
failure-free survival (DFFS), defined as either the time Fisher’s exact test for categorical variables. In addition,
to progression following T-VEC initiation or the time to select variables for DFFS and OS were further analyzed
disease recurrence from the time of initiation of therapy using the Kaplan–Meier method and log-rank tests.
for patients with a disease-free interval and overall survival Median follow-up duration was calculated from the
(OS). date of the initial T-VEC injection until the date of the
last known follow-up or death. All statistical analyses
2.3. T-VEC protocol and assessment of response
were performed using SAS 9.4 (SAS Institute Inc., US)
®
The treatment protocol for all included patients software.
involved in outpatient care with a standardized
injection regimen: injections were administered at week 3. Results
1, week 3, and subsequently every 2 – 3 weeks. Dosing 3.1. Patient characteristics and in-field response
was as per manufacturer guidelines, with the initial dose
of 1 × 10 plaque forming units (PFU)/mL administered We identified 18 eligible patients for inclusion since
6
into the target lesion(s), followed by injections at a 2018 (Table 1). Our study group included seven females
8
concentration of 1 × 10 PFU/mL. All injections were and 11 males, all of whom were white, precluding the
administered by either two surgical oncologists (JCG assessment of race/ethnicity as a covariate. The average
and CO) or one head-and-neck surgical oncologist (MS). age at the initiation of T-VEC therapy was 72 years
For subcutaneous lesions and involved lymph nodes, (range: 54 – 92). With a median follow-up of 12.7 months
injections were guided by ultrasound. Therapy was from the initiation of T-VEC therapy, the in-field ORR was
discontinued if there was clinical resolution of lesions 77.8%, with a complete response (CR) rate of 44%. Patient
with no further lesion to inject or further injections were age, sex, and NRAS mutation status did not demonstrate
deemed futile by the multidisciplinary treatment team. a significant association with in-field ORR nor did the
In cases where clinical resolution was unclear, a punch anatomic site of injection or type of lesion injected (Table 2).
biopsy of patients with residual skin pigmentation and/ BRAF mutation status was positive in five (27.2%) patients,
or needle or excisional biopsy of subcutaneous lesions with a 60% in-field response rate, compared with an 85%
or involved lymph nodes was conducted to confirm in-field response rate in BRAF wild-type patients, though
clinical and radiological resolution. this difference was not statistically significant (P = 0.53).
The majority of patients (66%) initiating treatment had
Response assessment categorized partial response as a stage III disease (initial or recurrent; stage IIIB: 2, stage
reduction in the size or number of measurable lesions with IIIC: 9, stage IIID: 1), while only six patients (33%) had
treatment, but residual lesions were still present, measured stage IV disease based on the American Joint Committee
either clinically (using a ruler) or radiographically on Cancer (AJCC) 8 edition staging guidelines. 12
th
(most commonly with ultrasound measurements). The
response was designated as complete if there was complete A majority of included patients had a history of prior
resolution upon clinical examination and/or radiological systemic therapy (n = 13), among whom 77% experienced
assessment, indicating no residual lesion to treat, or if any in-field ORR to T-VEC. Patients who had only one prior
measurable lesions were biopsied and found to have no line of systematic therapy achieved an ORR of 90%
viable tumor. For example, if a skin nodule flattened but (n = 10). Thirteen patients were treated concurrently
residual pigmentation remained, the pigmented area was with ICI and T-VEC, resulting in an ORR of 77%. While
biopsied to confirm the absence of residual viable tumor. prior systemic therapy did not demonstrate a significant
In cases of lymph nodes showing normalized size and association with response rate, there was a trend toward a
morphology on sonographic examination, fine needle worse in-field ORR for patients with an increasing number
aspiration was used to confirm the absence of residual of lines of systemic therapy (P = 0.18). None of the complete
viable tumors in the treated lymph nodes. responders had received ≥1 line of prior systemic therapy.

Volume 1 Issue 1 (2024) 97 doi: 10.36922/mi.3445