Intralesional (intratumoral) therapies have come a loooooong way, baby! I first began reporting on them in 2014. Here's a link to a zillion articles and posts: More than you ever wanted to know about intralesional therapy for melanoma!
As I embark on posting the things I feel are important from ASCO this year, I will add articles I have been collecting on each topic. We will start here, with all things intralesional ~
The following link takes you to a pretty good review of current state of the data regarding intralesional therapy. PV-10, Toll-like receptor agonists (TLR's), Intratumoral oncolytic viruses - to include: CAVATAK, Pexastimogene Devacirepvec (Pexa-Vec), HF10, PVS-RIPO, and TVEC are covered. Lots of interesting charts and trial results/status are covered, including data (when it exists) on combining these therapies with systemic treatments.
Intratumoral Immunotherapy Update 2019. Hamid, et al. Oncologist March 2020.
And here:
An Update on the Role of Talimogene Laherparepvec
(T-VEC) in the Treatment of Melanoma: Best Practices and Future Directions. Larocca, LeBoeuf, Silk, et al. Am J Clin Dermatol, 2020 Dec 21.
Talimogene laherparepvec (T-VEC) is the first agent approved
for cancer in the emerging class of oncolytic viral therapies. While T-VEC was
approved for the treatment of advanced melanoma in 2015, clinical utilization
has been hampered by rapid changes in the therapeutic landscape of melanoma
related to advances in both immune checkpoint blockade and targeted therapy,
cumbersome logistics involved in T-VEC administration, biosafety concerns, and
a perception that T-VEC has limited impact on uninjected, visceral disease.
However, with further survival follow-up from the phase III OPTiM
(OncovexGM-CSF Pivotal Trial in Melanoma), along with new real-world data and
consensus guidelines on safe administration of oncolytic viruses, a roadmap for
when and how to use T-VEC has been emerging. In addition, preliminary data have
demonstrated improved therapeutic responses to T-VEC in combination with immune
checkpoint blockade in patients with melanoma without additive toxicity. This
review provides an update on recent data with T-VEC alone and in combination
with other agents. The emerging data provide guidance for how to better utilize
T-VEC for patients with melanoma and identifies critical areas for clinical
investigation to expand the role of T-VEC in combination strategies for the
treatment of melanoma and perhaps other cancers.
There is this:
Oligoprogression After Checkpoint Inhibition in
Metastatic Melanoma Treated With Locoregional Therapy: A Single-center
Retrospective Analysis. Comito,
Leslie, Boos, et al. J Immunother, 2020
Oct.
Checkpoint inhibitors (CPIs) have demonstrated a heterogenous spectrum of response and disease progression that may not be fully captured by conventional response criteria, such as a limited degree of progression, known as oligoprogression, which could benefit from local treatment. We retrospectively analyzed data from all patients diagnosed with metastatic melanoma, who received CPI between January 2006 and March 2018 at Royal Marsden. We enrolled 36 patients who experienced progression in a maximum of 3 metastatic sites, after achieving disease control from therapy with CPI, and were radically treated with the locoregional approach. We carried out Kaplan-Meier analysis to obtain progression free-survival post-first oligoprogression (PFS-PO1), overall survival (OS) post-first oligoprogression, and OS estimates. The median time to oligoprogression from the start of CPI was 12 months. At a median follow-up of 34 months, the median PFS-PO1 was 32 months, with 50% of patients not progressed at the time of the data cutoff. The median OS-post-first oligoprogression was not reached. At a median follow-up of 52 months (from the first cycle of CPI), the median OS was not reached, with 75% of patients alive at the time of analysis. Univariate and multivariate analyses demonstrated that baseline American Joint Committee on Cancer stage IV M1a or M1b is associated with a longer PFS-PO1 compared with stage M1c or M1d. We observed that local therapy for oligoprogression after CPI can result in durable disease control, suggesting that locoregional treatment should be considered in patients being treated with immunotherapy. However, prospective evaluation, perhaps in randomized trials, is needed.
And this:
Durability of Complete Response to Intralesional
Interleukin-2 for In-Transit Melanoma.
Khoury, Knapp, Fyfe, et al. J
Cutan Med Surg. Feb 2021.
Background: Intralesional injection of interleukin-2 (IL-2)
for in-transit melanoma (ITM) is associated with a high rate of complete
response. However, there is a paucity of data on treatment durability and
long-term outcomes.
Methods: Consecutive patients with ITM, treated with
intralesional IL-2 therapy, at the Tom Baker Cancer Center were identified from
April 2009 to August 2019. All patients received at least 4 cycles (every 2
weeks) of IL-2 (5 MIU/mL). Complete response was defined as sustained (ie, 3
months) clinical complete remission of all known in-transit disease.
Results: Sixty-five patients were treated with curative
intent for in-transit disease with intralesional IL-2. Complete clinical
response was identified in 44.6% (29/65). In this subset of patients, the
median number of lesions per patient was 9 (range 1-40). The median total dose
of IL-2 was 0.8 mL (IQR 0.4-1.5) per lesion. One patient received isolated limb
infusion and 13.8% (4/29) received systemic immunotherapy as part of their
initial management. At a median follow-up of 27 months (IQR 16-59), 34.5%
(10/29) developed recurrent disease. Of these patients, 50.0% (5/10) presented
with synchronous in-transit and distant metastases. The median time to
recurrence was 10.5 months (IQR 5.8-16.3).
Conclusion: With long-term follow-up, 65.5% of complete
responders have a durable response to intralesional IL-2 therapy. In this
cohort of patients, local in-transit recurrence is most likely to occur within
12 months and is often associated with concomitant distant disease.
And finally, there is this from ASCO:
Talimogene laherparepvec with systemic immunotherapy
in melanoma: A real-world experience.
Behera, Chen, Song, et al. ASCO
2021.
Background: Talimogene laherparepvec (TVEC) is an FDA
approved oncolytic herpes virus for intralesional therapy in unresectable
metastatic melanoma. Real world data is sparse regarding the efficacy of TVEC
in combination with other systemic therapies used in melanoma. We present
outcomes of the largest single institution observational study of the off-label
use of TVEC in combination with systemic immunotherapy.
Methods: Patients
with metastatic melanoma receiving TVEC simultaneously with
ipilimumab-nivolumab (Ipi/Nivo) or single agent immunotherapy (either nivolumab
or pembrolizumab) were evaluated. The demographics, clinicopathological
characteristics, responses to injected lesions and remote metastatic lesions
were evaluated. Clinical documentation was used to assess improvement in injected
lesion size; time points for initial response and best response were
identified. Review of imaging by a radiologist was evaluated to assess
responses in remote metastatic lesions.
Results: A total of
67 patients receiving TVEC from 2016 to 2020 were evaluated, of which 50
remained evaluable after excluding Merkel cell carcinoma, patients on clinical
trial, TVEC monotherapy or those on BRAF-MEK inhibitors, and patients lost to
follow up. In total, 29 received systemic immunotherapy simultaneously with TVEC
and had been followed for at least a year, with a median follow-up time of 34
months (range, 12-56). At the time of analysis, 14 of 29 patients were alive. 6
of the 29 patients had received prior lines of therapy. Four patients received
Ipi/Nivo, while 25 patients received monotherapy including 9 on nivolumab and
16 on pembrolizumab. The median number of TVEC doses received was 6 (range,
2-55) with median average TVEC dose being 3.47 ml (0.5-4 ml). Median time to
initial local response was 6 weeks, whereas time to best local response was 14
weeks. Overall response rate in the injected target lesions was in 19 (66%),
with complete local response (CR) in 12 (41%), partial response (PR) in 7
(24%), and progressive disease (PD) in 8 (28%). The response rate in distant
non-injected lesions was 4 out of 16 (25%), 2 of which had previously
progressed on prior systemic therapy. Stable disease was observed in 8 (50%)
patients, and progression of disease in 4 (25%). The 1-year overall survival
rate in patients receiving TVEC with systemic monotherapy was 80%. Progression free survival at 1-year in the monotherapy group was
71.6%.
Conclusions: This is
the largest single institution, real world experience to our knowledge, which
assesses the efficacy of TVEC in combination with systemic immunotherapy. Our
cohort suggests that TVEC is an effective treatment in combination with
systemic immunotherapy, with a better overall survival observed with
combination TVEC and anti-PD1 than seen with historical data from clinical
trials of anti-PD-1 monotherapy.
As this mix of reports suggests, intralesional therapy can be used in several ways - as a treatment for one stubborn or new lesion in a person otherwise responding to their therapy; as an add on to pembro (Keytruda) or nivo (Opdivo) for folks with a relatively low burden of disease; or full bore combined with the ipi/nivo combo for those with more advanced disease. The response rates are not 100%, but they are something! And we all know, every bit helps!
Gonna shoot for getting a post up daily til done with ASCO (family, work and general life obligations withstanding)! My fearless and determined bestie had the tough job of going through ALL the ASCO reports!! When searching for intel on TWO cancers, that task is NOT for the faint of heart. I have gone through his collection and broken them down into topics. The reports will follow the pattern I have used here: Collected, but unshared articles, followed by the selection from ASCO 2021, with my thoughts in red.
I hope they will be of some use to a few of you. Take good care. - c
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