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SHORT COMMUNICATION
Induced Vitiligo due to Talimogene Laherparepvec Injection for Metastatic Melanoma Associated
with Long-term Complete Response
Pablo IGLESIAS 1# , Simone RIBERO 1,2# , Alicia BARREIRO 1 , Sebastian PODLIPNIK 1 , Cristina CARRERA 1 , Josep MALVEHY 1,3
and Susana PUIG 1,3
Dermatology Department, Hospital Clinic Barcelona, University of Barcelona, Villarroel 170, ES-08036 Barcelona, Spain, 2 Medical Sciences
Department, Section of Dermatology, University of Turin, Turin, Italy and 3 Centro de Investigación Biomédica en Red en Enfermedades
Raras (CIBERER), Barcelona, Spain. E-mail: [email protected] # Both authors contributed equally to this paper.
1
Accepted Oct 3, 2018; E-published Oct 3, 2018
Talimogene laherparepvec (T-VEC) (Imlygic, Amgen) is
the first oncolytic virus approved for use in therapy for
metastatic melanoma. T-VEC provides a treatment op-
tion for patients with limited metastatic disease. T-VEC
is a genetically modified, live, attenuated herpes simplex
virus type 1 designed to replicate in tumour cells and
promote an enhanced anti-tumour response (1) T-VEC is
administered by injection into cutaneous, subcutaneous
or nodal lesions, which are visible and/or palpable and/
or visualized by ultrasonography (2).
Other local management options have been used to
control metastatic disease in stage IIIB, but almost all have
shown only a local effect and rapid disease relapse (3, 4).
With T-VEC, responses occurred in injected and unin-
jected lesions, including a greater than 50% decrease in
size in 15% of uninjected visceral lesions.
The appearance of vitiligo has been described as an
adverse event after administration of immune checkpoint
inhibitors (5, 6). It has been reported as a marker of activity
of the drug and long-term results, inducing clinicians to
use it as a predictor of drug response (7). A T-VEC phase
II study has reported 85% adverse events, all of which
were grade 1 or 2. The appearance of vitiligo has been
described in 3 patients out of 50 (8), although no details
regarding duration and appearance have been reported.
CASE REPORTS
We describe here the appearance of a vitiligo phenomenon in the
context of T-VEC therapy. Both patients were enrolled in a clinical
trial after progression (Amgen 20120325, Eudra 2013-005552-
15). This trial consists of the injection of T-VEC in subcutaneous
nodules of melanoma. We performed the injection under ultraso-
nography. The patients had no active autoimmune disease or any
history of such disease in the clinical records (those would be
exclusion criteria for enrolment in the trial).
Patient 1. The first patient was a 47-year-old man who had had a
nodular ulcerated 3.2-mm melanoma, BRAF mutated, excised 3
years previously. The sentinel lymph node had a metastatic deposit
of 2 mm maximum tumour diameter and the 9 lymph nodes excised
at the complete lymph node dissection (CLND) were negative. Six
months after surgery he noticed the appearance of a nodule close to
the wide local excision scar (1 year after diagnosis of the primary
tumour) followed by other 5 lesions on the same leg, which were
confirmed to be cutaneous metastases. Radiological evaluation
confirmed the absence of any other tumour deposit and he was
enrolled in the trial 20120325, a total volume of 3.5 ml T-VEC at
108 PFU/ml was administered in 4 lesions.
doi: 10.2340/00015555-3061
Acta Derm Venereol 2019; 99: 232–233
A total of 14 administrations every 3 weeks were needed to com-
pletely shrink the metastases and to achieve a complete response.
He developed a flu-like reaction after each administration. Two
months after the last drug administration, hypochromic maculae
appeared in some of the treated lesions on his leg (Fig 1). The
patient remains in complete remission at 20 months. The size of
the vitiligo has been stable since its first appearance (Fig. 1B)
Patient 2. The second patient was a woman of 80 years, who
had a BRAF wild-type melanoma, 1.87-mm Breslow thickness,
excised from her right leg. Sentinel lymph node (SLN) biopsy
was not carried out. Two and a half years after the first diagnosis
she developed a lymph node metastasis in the groin and a meta-
stasis on the skin graft of the wide excision. She was submitted
to isolated limb perfusion with melphalan and tumour necrosis
factor (TNF)-α) with a complete response. This was maintained
for 14 months, when a new lesion (histologically confirmed)
appeared on the same leg and she was treated with 26 cycles of
T-VEC every 3 weeks, starting with an initial dose of 3 ml with a
complete response. She developed a flu-like reaction after every
administration. Two months after the last administration, some
hypochromic areas appeared on her face, neckline and dorsum of
her hands (Fig. 2). Seen under a Wood’s lamp, they were well de-
limited and hypopigmented, suggestive of a vitiligo phenomenon.
She remains in complete remission at 16 months. The vitiligo has
been stable in size since its first appearance.
DISCUSSION
T-VEC was US Food and Drug Administration (FDA)
approved for recurrent unresectable cutaneous and sub-
cutaneous melanoma in October 2015. In a recent phase
IIIB study, adverse events occurred in 93% of patients,
with the most common being fatigue, chills, and pyrexia;
grade ≥ 3 adverse events occurred in 24% of the T-VEC-
treated group (9).
Fig. 1. Case 1. (A) Well-defined hypochromic lesions with non-pigmented
hairs on the pretibial area. Those lesions appeared at the sites of the
previous melanoma metastases. (B) At 20 months from the complete
response the vitiligo plaques were still visible and stable in size, as seen
under Wood’s lamp.
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