To the Editor: We read with interest on Nguyen et al’s case of off-label use of intralesional talimogene laherparepvec (T-VEC) for Merkel cell carcinoma (MCC).
We recently had a patient with anti-PD-(L)-1 refractory metastatic MCC showing complete resolution of tumors with intralesional T-VEC. Our patient is a 74-year-old Caucasian woman initially diagnosed in November 2017 with stage IV oligometastatic MCC with tumors on the left cheek and left lateral thigh. Nearly 2 years after initial treatment with surgery and radiotherapy, she developed multiple recurrent MCC tumors on the left lower extremity. Over the course of 11 months, she was treated with multiple systemic monotherapies including an investigational anti-PD-(L)-1 antibody, a somatostatin analogue, and avelumab. Both attempts at PD-(L)-1 blockade were compromised by grade 3 immune-mediated toxicities that required prolonged immunosuppressive therapy and compromised treatment response.
In December 2021, the patient developed rapid disease progression with enlargement of preexisting MCC tumors and multiple new nodules on the left leg. Due to contraindications to systemic immunotherapy, she was treated with intralesional T-VEC beginning February 2022.
A priming dose of 1 mL (1 million pfu/mL) was delivered to one of the left thigh lesions (Fig 1, A). Shortly thereafter, the patient was urgently referred for palliative radiation of the left thigh due to rapid enlargement and ulceration of several large, beefy nodules. Following her first dose of treatment level (100 million pfu/mL) T-VEC and additional radiation therapy, the patient had complete resolution of the thigh tumors (Fig 1, B). Concurrently, T-VEC was administered to 4 new, smaller nodules on the medial calf (Fig 2, A), none of which received radiation. After the second dose, the patient showed an impressive clinical response with complete resolution of all injected tumors on the lower leg (Fig 2, B). Our patient continues to show no evidence of disease for over 7 months after T-VEC initiation.
Fig 1.
Multiple Merkel cell carcinoma tumors on the left thigh, as seen at baseline (A) and post-treatment (B) after concurrent talimogene laherparepvec and radiation therapy to the left thigh.
Fig 2.
Multi-focal Merkel cell carcinoma nodules on left lower leg as seen at baseline (A) and post-treatment (B) after 3 doses of intralesional talimogene laherparepvec (T-VEC). The patient, with prior disease progression and major toxicities with PD-1 (Programmed death-1)/PD-L1 (Programmed death ligand-1) blockade, experienced an overall complete response with TVEC, which is ongoing at 7+ months after treatment initiation.
Toxicities were limited to transient fevers, body chills, and fatigue that resolved with Tylenol. After the third cycle, she developed a self-limited, erythematous rash on the face and chest that improved with oral cetirizine and topical triamcinolone.
Intralesional T-VEC has been well studied in melanoma, both as monotherapy and in combination with PD-1 inhibitors.1,2 Our case adds to the previous case reports on T-VEC in MCC (Table I) and highlights its potential as an alternative immunotherapy option for patients who may have anti-PD-(L)-1 refractory disease or may have serious contraindications to receiving systemic immunotherapy.3, 4, 5, 6, 7, 8, 9 Our case also suggests that T-VEC can lead to rapid regression of injected MCC tumors and has potential to provide systemic control beyond just the injected tumors. It can also be administered concurrently with radiation therapy for a possible synergistic effect. In comparison to alternatives (eg, cytotoxic chemotherapy), T-VEC has a favorable side effect profile.
Table I.
Summary of studies reporting T-VEC use in MCC
| Author | Year | Study design | Treatment regimen | Number of patients | Reported outcome |
|---|---|---|---|---|---|
| Casale et al3 | 2022 | Case report | T-VEC | 1 | Complete response |
| Hirotsu et al4 | 2021 | Case report | T-VEC | 1 | Complete response at 5-mo follow-up after last T-VEC dose |
| Nguyen et al5 | 2019 | Case report | T-VEC | 1 | Complete response >2 y in injected and uninjected lesions |
| Knackstedt et al6 | 2019 | Case report | T-VEC + anti PD-1/PD-L1 therapy | 2 |
|
| Westbrook et al7 | 2019 | Case series | T-VEC | 4 | All patients had complete response with a median progression free survival of >16 mo |
| Lara et al8 | 2018 | Case report | T-VEC + anti PD-1 therapy | 1 | Complete response |
| Blackmon et al9 | 2017 | Case report | T-VEC | 2 |
|
MCC, Merkel cell carcinoma; PD-L1, Programmed death ligand-1; T-VEC, talimogene laherparepvec.
In summary, T-VEC may be an appealing option for patients with superficial injectable MCC tumors who may not have good systemic immunotherapy options due to prior disease progression or major contraindications.
Conflicts of interest
None disclosed.
Footnotes
Funding sources: None.
IRB approval status: Not applicable.
Patient consent: A statement that patient consent forms are on file: Consent for the publication of all patient photographs and medical information was provided by the authors at the time of article submission to the journal stating that all patients gave consent for their photographs and medical information to be published in print and online and with the understanding that this information may be publicly available.
Key words: immunotherapy, Merkel cell carcinoma, oncolytic viral therapy, Programmed cell death-1, talimogene laherparepvec.
References
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