Sunday, July 27, 2014

More Intralesional therapies for melanoma....abstracts from ASCO 2014

Wrote this post up in June, but with so much new info about anti-PD1 EAP's (from Merck and BMS) as well as the EAP for the ipi/nivo combo and all the other melanoma news...this got put on the back burner.  I still love the idea of intralesional therapy for folks with accessible tumors.  I don't think it will ever be a cure-all, but feel it holds real promise especially when combined with more systemic therapies.  This is what Weber and Ribas had to say about one in their chat:

Injectable therapies
Ribas:  ...a randomized trial of an injectable virus called T-VEC compared with granulocyte-macrophage colony stimulating factor (GM-CSF).

Weber:  ...the responses were 16% vs 2%.  Obviously you don't expect any responses with GM-CSF, so 2% would be essentially zero.  A 16% response rate overall in a patient with injectable local-regional disease plus systemic disease is pretty modest....that is close to being able to show that there are benefits to giving this injectable therapy....Injectable therapies are making a comeback.....eons ago we were injecting BCG, interferon, and IL-2 into local-regional melanoma there are some interesting drugs, and T-VEC is one of them.  I see this as a niche drug that would be best used to prime the immune system and follow up with a drug such as pembrolizumab, nivolumab, ipi, or a combination of those....that's where I see intralesional therapy going.

2 abstracts:

Tumor response and patient survival after intralesional therapy with low-dose GM-CSF and IL-2 in metastatic and primary cutaneous melanoma:  An exploratory study.
Abstract c20002, Elias and Sharma

Patients with dermal and subdermal mets, no matter the extent of their disease or previous therapy, were given intralesional GM-CSF once a week for 4-6 weeks. If no complete clinical response was noted at the injection sites, they were then given intralesional IL-2 for the same length of time. 
Results:  4 patients with more than 126 small in-transit mets, each lesion measured a few mm to up to 1 cm.  All had a complete response confirmed pathologically 6-8 weeks after cessation of therapy, with disease free survival of 37-54 months.  Another 3 patients with large sclerotic skin lesions failed to respond to either cytokine.  One of 2 patients with distant mets who also had palpable subdermal tumors had complete response of all mets. This patient is alive and disease free for over 48 months.  Conclusion:  [After examination of the tissues resected after treatment...] Intralesional therapy seemed to utilize the tumor site as a source for tumor-specific antigens giving rise to autoimmunization with strong antitumor response...

A phase I study with LTX-315, an immunogenic cell death inducer, in patients with transdermally accessible tumors.
Abstract 3067, Brunsvig, Aamdal, Kolstad, et al (London and Oslo)

LTX-315 is a chemically modified 9-mer peptide...and induces the release of potent danger signals and tumor-associated antigens.  Preclinical animal studies have demonstrated that treatment of a single tumor with LTX-315 generated systemic anti-tumor immune response that eradicated distant lesions and prevented recurrence following tumor rechallenge.  Patients received weekly ultrasound guided injections of LTX-315 into a single tumor for a max of 6 injections (dosage varied).  14 patients with lymphomas, malignant melanomas or breast cancer were enrolled.  Tumor necrosis was seen in 5 patients.  2 patients had a 50% reduction in tumor volume.   A new intratumoral study at 4 European sites is ongoing.  Clinical trial number - NCT01058616.

Don't forget good old Rose Bengal (PV-10) as well.  Sort of wish my buddy, J, could have had at least one of these injected into any residual tumors while surgeons were meddling around in there!!!  What the heck?  That's a thought for a trial!  When a melanoma patient has to undergo surgery....inject one of these bad boys into any accessible tumor that is not removed!  Why not?  Just a thought! - c

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