Wednesday, March 21, 2018

In-transit melanoma. Two "new" treatment options!

In-transit mets from melanoma can be very difficult to deal with.  This collection of posts covers treating them with limb perfusion therapy and earlier studies with PV-10:  Studies looking at treating in-transit mets

Now there's this: 

Successful Treatment of Nivolumab-Resistant Multiple In-Transit Melanomas with Ipilimumab and Topical Imiquimod. Fujimura, Kambayashi, Sato, et al.  Case Rep Oncol. 2018 Jan 4.

Simultaneous or sequential, planned administration of ipilimumab could significantly enhance the antitumor effects of nivolumab in advanced melanoma patients. On the other hand, the efficacy of ipilimumab for nivolumab-resistant advanced melanoma is extremely poor. Therefore, additional supportive therapy for anti-PD-1 antibody therapy-resistant advanced melanoma has been widely investigated. In this report, we describe a case of multiple in-transit melanomas developing in a nivolumab-resistant patient successfully treated with ipilimumab in combination with imiquimod. Our present case suggested a possible therapy for nivolumab-resistant multiple in-transit melanomas using ipilimumab in combination with topical imiquimod.

And this:

Intralesional PV-10 for the treatment of in-transit melanoma metastases-Results of a prospective, non-randomized, single center study. Read, Smith, Thomas, et al.J Surg Oncol. 2018 Mar 12.
Patients with in-transit melanoma metastases frequently experience high rates of recurrence, limited overall survival and reduced quality of life. After promising results within a Phase II, multi-center study, PV-10 treatment was continued at our institution for patients with in-transit disease.

An open-label, non-randomized, prospective study was performed at the Princess Alexandra Hospital, Queensland, Australia. Patients were treated with PV-10 in accordance with the treatment protocol established during a previous Phase II study. The primary outcome was the complete response of treated lesions.

Forty-five patients were enrolled over a total of 82 treatment episodes from July 2008 to December 2015. With sequential PV-10 treatments the complete response rate was 42% and overall response rate 87% on an intention to treat analysis. The median follow-up duration was 22 months and the median overall survival was 25 months from first PV-10 treatment. Having fewer than 15 metastases at the time of treatment was associated with a complete response.

Intralesional PV-10 provided rapid lesion-specific ablation of melanoma metastases with well-tolerated local effects and minimal systemic adverse events. This therapy should be considered for patients with multiple accessible deposits within the spectrum of low to moderate disease volume.

While the entire report is included in the link above....for comparison there was this in 2017:

Results of a phase II, open-label, non-comparative study of intralesional PV-10 followed by radiotherapy for the treatment of in-transit or metastatic melanoma. Foote, Read, Thomas, et al. J Surg Oncol. 2017 Feb 23. 

Fifteen patients were enrolled and thirteen completed both treatment components. The overall response rate was 86.6% and the clinical benefit was 93.3% on an intention to treat analysis. The median follow up duration was 19.25 months. Size of metastases (less than10 mm) predicted lesion complete response (74.6%). Treatment was well tolerated with no associated grade 4 or 5 adverse events.  

And this from

Intralesional PV-10 for in-transit melanoma-A single-center experience.  Lippey, Bousounis, Behrenbruch, et al.  J Surg Oncol. 2016 May 30. 

Nineteen patients with in-transit melanoma were treated with intralesional PV-10 between 2010 and 2014. Disease control (complete or partial response or disease stability) was achieved in 68% of patients with 26% having a complete response.

Overall, while all these studies look at relatively small numbers, the results are certainly hopeful.  As is usual in melanoma it seems that combining treatments (radiation with intralesionals, immunotherapy with topicals) may boost response even more.  It is a tough road, but ratties are moving us forward bit by bit!  - c


  1. Any comment or info on Checkmates CMP-001?

  2. No, I haven't seen anything come out about that trial in particular. Doesn't mean it isn't there, but I haven't seen it. Here is a link that addresses some other CPG-ODN agonists to TLR9 (specifically the post about the intralesional SD-101 and the other about CpG-B).

    I'll keep an eye out for the other though and post if I find anything. Take care. c

  3. There are these:

    But they probably don't provide the info you are looking for. c

    1. Thx Will have to wait for the AACR presentation in Chicago Appreciate what you do.M