T-VEC in melanoma, after progression on immunotherapy and BRAFi with good results! 3 case reports...

I have been a fan of intralesional (also called intratumoral) therapies for some time...esp in combination with systemic therapy, noting in a prior report ~ "These drugs are injected directly into a relatively superficial melanoma tumor.  They have been found to be effective in not only eradicating the tumor into which they have been injected, but 'by-stander' lesions as well. Researchers feel that they have the most promise when they are combined with a systemic treatment like immunotherapy."

These drugs include:  T-VEC, PV-10, CAVATAK, HF10, SD101 and IMO-2125 (both TLR agonists), ISF35 (a CD40 agonist), and even IL2 has been used in this fashion.  Here's a link to bunches of reports on all of these:  ALL the intralesionals!!!

Here are multiple reports on T-VEC in particular:  All things T-VEC (talimogene laherparepvec)

Now...here are three case reports on melanoma peeps who had failed multiple therapies but gained a response with T-VEC...

Potential clinical and immunotherapeutic utility of talimogene laherparepvec for patients with melanoma after disease progression on immune checkpoint inhibitors and BRAF inhibitors. Chesney, Imbert-Fernandea, Telang, et al. Melanoma Res. March 20, 2018.

Talimogene laherparepvec is a genetically modified herpes simplex virus type 1-based oncolytic immunotherapy for the local treatment of unresectable subcutaneous and nodal tumors in patients with melanoma recurrent after initial surgery. We report on two patients with melanoma who, after progression on numerous systemic therapies, derived clinical benefit from talimogene laherparepvec in an expanded-access protocol. Intralesional talimogene laherparepvec (day 1, greater than/= to 4 ml 10 PFU/ml; after 3 weeks, greater than/= to 4 ml 10 PFU/ml every 2 weeks) was administered until complete response, no injectable tumors, progressive disease, or intolerance occurred. Patient 1 was 71 years old, had stage IIIB disease, and had previously received granulocyte-macrophage colony-stimulating factor, vemurafenib, metformin, ipilimumab, dabrafenib, trametinib, and pembrolizumab. Patient 2 was 45 years old, had stage IIIC disease, and had previously received nivolumab/ipilimumab combination therapy. There were marked reductions in the number and size of melanoma lesions during treatment with talimogene laherparepvec. Both patients experienced mild-to-moderate nausea and vomiting, which were managed using ondansetron, metoclopramide, and pantoprazole. Both patients completed treatment with talimogene laherparepvec in the expanded-access protocol on 24 November 2015, but received talimogene laherparepvec in clinical practice. Patient 1 continues to receive therapy (greater than 60 weeks); patient 2 experienced a complete response at 23 weeks. Immunohistochemistry of a biopsied dermal metastasis from patient 1 showed a marked infiltration of CD4 and CD8 T cells after 1 year of treatment. Talimogene laherparepvec was active in patients with advanced melanoma with disease progression following multiple previous systemic therapies; no new safety signals were identified.

...and the final peep....

Complete intracranial response to talimogene laherparepvec (T-Vec), pembrolizumab and whole brain radiotherapy in a patient with melanoma brain metastases refractory to dual checkpoint-inhibition. Blake, Marks, Gartrell, et al. J Immunother Cancer. 2018 Apr 6.

Immunotherapy, in particular checkpoint blockade, has changed the clinical landscape of metastatic melanoma. Nonetheless, the majority of patients will either be primary refractory or progress over follow up. Management of patients progressing on first-line immunotherapy remains challenging. Expanded treatment options with combination immunotherapy has demonstrated efficacy in patients previously unresponsive to single agent or alternative combination therapy.

We describe the case of a patient with diffusely metastatic melanoma, including brain metastases, who, despite being treated with stereotactic radiosurgery and dual CTLA-4/PD-1 blockade (ipilimumab/nivolumab), developed systemic disease progression and innumerable brain metastases. This patient achieved a complete CNS response and partial systemic response with standard whole brain radiation therapy (WBRT) combined with Talimogene laherparepvec (T-Vec) and pembrolizumab.

Patients who do not respond to one immunotherapy combination may respond during treatment with an alternate combination, even in the presence of multiple brain metastases. Biomarkers are needed to assist clinicians in evidence based clinical decision making after progression on first line immunotherapy to determine whether response can be achieved with second line immunotherapy.

Now...these abstracts describe only 3 peeps.  Patient #1 is still with us a year later and, given the T cell response noted, seems to be benefiting.  Patient #2 attained a complete response.  Patient #3 attained a complete response in the brain and partial in the body.  (I still really hate it when melanoma patients - or anybody really - has to resort to WBR, but desperate times call for desperate measures.) 

So...for what it's worth.  Sounds like something I would certainly be interested in should I have the need.  Hang tough ratties!!! - c