H/t a shareholder and regular hatter for access to the above paper. Bolding-in-paragraph and underlined emphasis below is mine.
[From the end of the paper] "Synopsis: This paper reviews a single metropolitan cancer hospitals experience with PV-10 for the treatment of in-transit melanoma. Over a 4-year period, we have treated 19 patients with PV-10 for melanoma and achieved disease control in 68% of patients. We find it a helpful tool in our armory for local control of this often-difficult clinical scenario."
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"Toxicity: The majority of treatments (73%, 24/33) were well tolerated without any reported side effects. Edema, pain and erythema were the most common side effects, although these were minor in severity, limited in duration, and easily managed by simple analgesia. Five patients required opiate analgesia for pain associated with PV-10 injection.
One patient was readmitted to hospital 1 week following treatment with lower limb cellulitis requiring intravenous antibiotics for 2 days. This patient was obese and elderly and the cellulitis arose in the area of recent injection."
"Treatment Response: After a median follow up of 11.7 months, disease control was achieved in 63% of patients. Five patients (26%) achieved a complete response, another five (26%) patients achieved a partial response, and two patients had stable disease (11%) at the time of last follow-up. Seventy-four percent (14/19) of patients had a clinical response at time of first follow-up (median time 21 days); range 8–91 days. Younger patients and those with smaller lesions were more likely to respond to treatment (Table III). The number of injected lesions and the time from primary diagnosis to treatment were not predictive of response.
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Ten patients did not have all lesions injected, primarily due to the number of lesions present. A bystander response was noted in un-injected lesions in 50% of patients who did not have all their lesions directly injected (Table II). After a median follow up of 11.7 months, eight patients had died
from metastatic melanoma."
"DISCUSSION: This single-center retrospective review demonstrates that intralesional PV-10 is an effective, safe, and well-tolerated treatment option for patients with ITMs and loco-regional recurrence of melanoma. Treatment was delivered to a group of patients who were elderly (median age 82 years) and in many cases considered inappropriate for more aggressive and potentially toxic therapies such as ipilimumab or isolated limb infusion.
There have been several previous reports of success with intratumoral injection of PV-10, providing local control in this group of patients with an acceptable toxicity profile. There is still a lack of data about durability of PV-10 as well as a lack of long-term survival data. The largest published study assessing the use of PV-10 in the setting of refractory melanoma published in 2014 analyzed 80 patients from seven international sites. In this study, a 52% overall response rate and 26% complete response rate were described which is comparable to the overall response rate of 63% and complete response rate of 26% in the current series as well as in another previously published single-center series (Table IV).
The effective treatment options for metastatic and locoregional inoperable disease melanoma have rapidly improved over the last 5 years. With the introduction of novel systemic agents targeting immune checkpoints (ipilimumab, pembrolizumab, nivolumab), and mutations in the MAP kinase
pathway (dabrafenib and trametinib), the treatment options for patients with unresectable metastases have increased and the prognosis for these patients has significantly improved. However, these agents may be associated with significant toxicity and in the case of PD-1 targeted therapy require frequent hospital visits for infusions. Intralesional PV-10 compares favorably with other
intralesional therapies including talimogene laherparepvec (T-VEC) which in the recently published OPTiM study demonstrated on overall response rate of 26.1%. It is important to note that the
patient population in the OPTiM study had more advanced disease than the population in the current study, and the response rate for patients with all lesions injected lesions with T-VEC was 33%. For an
elderly patient with ITM, a simple and effective local therapy with minimal side effects is an attractive option. In our center, the use of ILI has steeply decreased with the availability of PV-10.
In the modern era of effective systemic therapies, patient selection for intralesional therapy is critical. Previously described factors predictive of response include the presence of ulceration, blistering, eschar, or pain following injection. In the current study, lesion size was also found to be predictive. Of the five patients who achieved a complete response, the average lesion diameter was 3 mm compared to the cohort average size of 6.3 mm. We did not specifically collect data on eschar formation but anecdotally have seen significant ulceration and eschar in most responders which may represent a brisk immune response to treatment or a direct toxic
Aside from the local toxicity of pain and edema and an isolated report of photosensitivity, PV-10 remains a very safe treatment option. As compared to radiotherapy, PV-10 has the advantages of allowing a wider field of treatment which may be repeated if necessary. A successful combination of radiotherapy and intralesional PV-10 has been reported and may warrant further
The limitations to this study are the retrospective nature and the variable treatment regimens which were tailored to patients according to social, geographic, and oncological factors. As our cohort consisted of elderly and comorbid patients, we often limited their required visits to hospital which is reflected in the short follow-up intervals.
There are a growing number of options for the treatment of unresectable in-transit disease and choice depends on many factors including availability of treatment, patient suitability, and disease factors. Intralesional PV-10 compares favorably in that it is well tolerated especially in an elderly patient or one with significant comorbidities.