Intralesional Immunotherapy Research Articles

Efficacy of intralesional Candida antigen immunotherapy in treatment of recalcitrant warts.

Efficacy of intralesional Candida antigen immunotherapy in treatment of recalcitrant warts.

LBA66 - Primary 2-year (yr) results of a phase II, multicenter, randomized, open-label trial of efficacy and safety for talimogene laherparepvec (T-VEC) neoadjuvant (neo) treatment (tx) plus surgery (surg) vs surg in patients (pts) with resectable stage IIIB-IVM1a melanoma

BackgroundRisk of recurrence and death remain high for pts with advanced melanoma after resection. TVEC, an intralesional immunotherapy for advanced melanoma, selectively replicates in tumors and enhances systemic antitumor immune response. We examined the impact of neo T-VEC in resectable metastatic melanoma. MethodsPts with resectable stage IIIB-IVM1a melanoma and ≥ 1 injectable cutaneous, subcutaneous or nodal lesions were randomized 1:1 to 6 doses/12 wks of neo T-VEC then surg (Arm 1) vs surg alone (Arm 2). T-VEC was given until surg, no remaining injectable tumors or intolerance. The primary endpoint per protocol was recurrence-free survival (RFS) at 2-yrs, with events defined as first of local, regional or distant recurrence or death due to any cause after surg in the ITT set. Per protocol, pts who withdrew prior to surg or had a non-R0 resection were counted as an RFS event at randomization. An additional sensitivity analysis that did not count non-R0 events at baseline per conventional RFS calculation was also conducted. ResultsDemographics, tx status and safety for the 150 pts analyzed has been reported (Dummer et al., ASCO 2019). Median follow-up (range) was 31.2 (0.1, 49.9) mos. Per protocol, 29.5% of pts in Arm 1 and 16.5% of pts in Arm 2 remained recurrence free at 2 yrs (HR 0.75, P=0.07). 50.5% of pts in Arm 1 and 30.2% of pts in Arm 2 (HR 0.66, P=0.038) remained recurrence free at 2 yrs in the additional sensitivity analysis. 2-yr overall survival (OS) rates were 88.9% in Arm 1 and 77.4% in Arm 2 (overall HR 0.49, P=0.050). In Arm 1, T-VEC resulted in a 3x increase in intratumoral CD8+ cell density (P<0.001) and an increase in PD-L1 (P≤0.05). CD8+ density and PD-L1H-score were higher post-tx in Arm 1 vs Arm 2 (P<0.001). Increased intratumoral CD8+ density post-tx correlated with longer RFS in the sensitivity analysis and OS. ConclusionsIn the largest randomized trial of neo tx in resectable stage IIIB-IVM1a melanoma, neo T-VEC improved 2-yr RFS and OS. T-cell influx and PD-L1 upregulation after T-VEC tx support a role for the adaptive immune system consistent with the mechanisms of action. Clinical trial identificationNCT02211131, release date: August 7, 2014; EudraCT: 2014-001146-13. Editorial acknowledgementMedical writing support was provided by Sarah K Madsen (Amgen Inc.). Legal entity responsible for the studyAmgen Inc. FundingAmgen Inc. DisclosureR. Dummer: Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship outside the submitted work: Novartis; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship outside the submitted work: Merck Sharp & Dohme (MSD); Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship outside the submitted work.: BMS; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship outside the submitted work: Roche; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship outside the submitted work: Amgen Inc; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship outside the submitted work: Takeda; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship outside the submitted work.: Pierre Fabre; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship outside the submitted work: Sun Pharma; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship outside the submitted work: Sanofi; Advisory / Consultancy, Intermittent, project focused consulting and/or advisory relationship outside the submitted work: Catalym. D.E. Gyorki: Honoraria (self), Travel / Accommodation / Expenses: Amgen Inc.. J. Hyngstrom: Advisory / Consultancy, Reviews of general surgery research articles every 2 months for Practical Reviews of General Surgery: Ebix. A. Berger: Speaker Bureau / Expert testimony: Cardinal Health; Advisory / Consultancy, Speaker Bureau / Expert testimony: Castle Biosciences. R. Conry: Speaker Bureau / Expert testimony: Merck; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Amgen Inc.; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Array; Speaker Bureau / Expert testimony: Regeneron-Sanofi. L. Demidov: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy: Merck Sharp & Dohme; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Roche. A. Sharma: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen Inc.. S.A. Treichel: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen Inc.. K. Gorski: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen Inc.. A. Anderson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen Inc.. M. Faries: Advisory / Consultancy: Delcath Systems Inc.; Advisory / Consultancy: Pulse Bioscience; Advisory / Consultancy: Novartis. M.I. Ross: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Amgen Inc.; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Research grant / Funding (self), Travel / Accommodation / Expenses: Provectus; Travel / Accommodation / Expenses: Castle Biosciences; Travel / Accommodation / Expenses: Novartis.

Role of mannose binding lectin in response to candida antigen immunotherapy of warts

Background Warts is the commonest cutaneous manifestation of human papillomavirus (HPV) infection. Intralesional Candida antigen immunotherapy is used for wart treatment. Aim To identify the role of mannose binding lectin (MBL) in susceptibility to HPV infection and to explore the relationship between MBL and response to intralesional Candida antigen immunotherapy of wart. Patients and methods A case-control study was enrolled with 96 participants; 48 wart cases and 48 healthy controls. MBL serum level assay baseline and after six settings of intralesional candida antigen injection was done by ELISA technique. MBL2 gene exon 1 codon 54 polymorphism was detected by using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Results A statistically significant difference in MBL serum level between wart cases and controls was found. An association between MBL2 exon1 codon 54 polymorphism and susceptibility to HPV infection and development of warts was proved. Carriage of genotype AB was more frequent wart cases (95.8%) than in controls (20.8%). No statistical significance association could be found between the therapeutic response to Candida antigen immunotherapy in wart cases and MBL as regards its serum level and genotypes. Conclusions MBL play an important role in host defense against HPV infection

A comparative study of topical cantharidin and intralesional PPD to treat molluscum contagiosum

Background: The immune system plays an important part in the clearance of molluscum contagiosum (MC) and, therefore, there has lately been a trend in using immunotherapy in MC therapy. Tuberculin-purified protein derivatives (PPDs) and topical cantharidin have not earlier been compared with their effectiveness in therapyAim: The aim of this research was to determine the effectiveness and security of intralesional immunotherapy in the therapy of MC with tuberculin PPD versus topical cantharidinPatients and methods: Twenty patients with various MC lesions received topical cantharidin as control (group A) and 20 MC patients received intralesional tuberculin PPD following prior intradermal immunity tests (group B‏).Results: Complete clearance of lesions was detected in 90.0% of patients in the cantharidin group; the partial response was detected in10.0% of the patients. However, in the PPD group, 85% of the patients showed a complete response and 15% showed a partial response, with no significant difference in the clinical response between the two groups. Mild side effects were detected‏.Conclusion: The results suggest that intralesional PPD and topical cantharidin 0.7% are effective and safe treatment modalities, but benefits of intralesional PPD is being a simple, effective and safe treatment with tolerable pain and can be an alternative treatment for multiple resistant types‏.

Intralesional Vitamin D3 versus Purified Protein Derivatives in The Treatment of Multiple Cutaneous Warts: Comparative Study

Background: Viral warts are caused by human papillomavirus. Many therapeutic options are available for treating warts. Newer and effective treatments include intralesional immunotherapy, has been tried in the recent times with variable success rates. Objective: The aim of this study was to compare the effect of intralesional vitamin D3 versus purified protein derivative (PPD) in the treatment of multiple cutaneous warts. Methods: A total of 62 patients were included in the study, each patient had at least 3 common warts, one or more of them injected with 0.1 of intralesional PPD, one or more injected with 0.5 of vitamin D3 and one or more were control according to number of warts of each patient and up to 4 sessions. The clinical assessment was done by photographic measurements at baseline, before each treatment session, and after the completion of treatment. Results: In PPD-injected lesions. 43 patients (69.4%) showed complete clearance (100%) and 13 patients (20.9%) showed partial response (25% - 99%). While, in vitamin D3-injected lesions, 22 patients (35.5%) showed complete clearance while 21 patients (33.9%) showed partial response. On comparing between PPD, vitamin D3 and control, both PPD and vit D3 were statistically significant compared to control and PPD was more statistically significant than vit D3 (P3 = 0.019) in effectiveness and less in recurrence rate. Conclusions: PPD and vitamin D3 were found to be effective, well-tolerated modalities of treatment of multiple common warts. Intralesional PPD was more statistically significant in effectiveness and less in recurrence rate than intralesional vitamin D3.

Abstract CT119: Trial in progress: First in human Phase I study using a plasmid DNA coding for Emm55 streptococcal antigen (IFx-Hu2.0) in patients with unresectable stage III or stage IV cutaneous melanoma

Abstract Background: In the past few years, anti-PD-1 and anti-CTLA4 immune-based therapeutics have revolutionized melanoma therapy, but many patients do not respond. The IFX-Hu2.0 formulation consists of a vector encoding a streptococcal membrane protein Emm55 and a cationic polymer. When IFX-Hu2.0 is injected into murine or equine melanomas, tumors regress. Transfection of the emm55 vector into B16 melanoma cells resulted in expression of Emm55 as measured by RT-PCR. Systemic immune responses elicited by IFx-Hu2.0 in B16 bearing mice were CD4 and CD8 T cell dependent and antigen specific. Antigen specificity was tested utilizing a M05 tumor model (B16 cells transfected with the Ovalbumin gene). Mice received 5*106 OT-1 T cells (T cells that have transgenic TCR that recognizes OVA). Tumors were harvested (48 hours) and tetramer specific CD8+ T cells were increased in treated mice. Given this preliminary data, we proceeded to design a first in human Phase I feasibility trial (single dose level with no dose escalation) to test IFx-Hu2.0 use as an intralesional immunotherapy for melanoma to provoke the immune response by facilitating Emm55 antigen surface expression and enhancing tumor recognition. Methods: The primary objective is to assess the safety, tolerability, and feasibility of intralesional injection with IFx-Hu2.0 as a monotherapy in 6 adult patients (&amp;gt;18 years) with unresectable stage III or stage IV cutaneous melanoma lesions. To be eligible, a patient must have at least 1 injectable lesion and 1 un-injected lesion available for biopsies, but up to 3 lesions may be injected. Unlike other trials for melanoma, only 3 mm cutaneous lesions are needed. Patients must have failed, refused or been deemed not candidates for one form of systemic anti-PD-1-based immunotherapy as well as BRAF inhibition, if BRAF V600 mutated. In addition, patients with unresectable cutaneous, subcutaneous, and nodal melanoma lesions recurrent after initial surgery must have failed, refused or not candidates for TVEC. Patients may be enrolled with brain metastases (&amp;lt;1 cm) as long as they are receiving radiation with a life expectancy of &amp;gt;3 months, but may not be receiving concurrent chemotherapy/biological therapy, have uncontrolled hepatitis B/C/HIV infection, or have a history of organ allograft transplantation. Concurrent radiotherapy is allowed at distant sites from the injected lesion. 40 mL of peripheral blood will be collected prior to treatment and at the follow-up visit (28 days) for correlative studies to complement the preclinical murine models. Patients responding to therapy may continue dosing every 3 weeks thereafter. Feasibility is defined as the ability to treat five of the six patients enrolled without dose-limiting toxicity (28 days). As of January 2019, 1/6 of the planned patients have been enrolled. Clinical trial registry number: NCT03655756. Citation Format: Joseph Markowitz, Krithika N. Kodumudi, Deanryan B. De Aquino, Vernon K. Sondak, Shari Pilon-Thomas. Trial in progress: First in human Phase I study using a plasmid DNA coding for Emm55 streptococcal antigen (IFx-Hu2.0) in patients with unresectable stage III or stage IV cutaneous melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT119.

Extragenital cutaneous warts - clinical presentation, diagnosis and treatment.

Extragenital cutaneous warts are benign epidermal tumors caused by human papillomaviruses (HPVs) and a frequent reason for patients to consult a dermatologist. Depending on wart type and site involved, the clinical presentation is highly varied. Given that warts represent a self-limiting condition, a wait-and-see approach may be justified. However, treatment is always indicated if the lesions become painful or give rise to psychological discomfort. Factors to be considered in this context include subjective disease burden, patient age, site affected, as well as the number and duration of lesions. Destructive treatment methods involve chemical or physical removal of diseased tissue. Nondestructive methods consist of antimitotic and antiviral agents aimed at inhibiting viral proliferation in keratinocytes. Some of the various immunotherapies available not only have localized but also systemic effects and are thus able to induce remission of warts located at any distance from the injection site. Especially patients with warts at multiple sites benefit from this form of treatment. Intralesional immunotherapy using the mumps-measles-rubella (MMR) vaccine is a particularly promising option for the treatment of recalcitrant warts in adult patients. For children, on the other hand, HPV vaccination is a novel and promising approach, even though it has not been approved for the treatment of cutaneous warts. At present, there is no universally effective treatment available. Moreover, many frequently employed therapies are currently not supported by conclusive clinical trials.

Intralesional Measles, Mumps, and Rubella Vaccine for Cutaneous Warts: A Systematic Review and Meta-analysis

Background. Warts, caused by the human papilloma virus (HPV), are mucocutaneous proliferations controlled by cell-mediated immunity. Intralesional immunotherapy with measles, mumps, and rubella (MMR) vaccine, is postulated to induce a higher immune response for clearance of lesions.&#x0D; Objective. To assess the efficacy, safety and effect on recurrence of intralesional MMR vaccine for the treatment of warts.&#x0D; Methods. We searched online databases for randomized controlled trials on intralesional MMR vaccine for warts. Effects measured were the complete clearance of target and distant warts, adverse events noted and recurrence after treatment duration.&#x0D; Results. Four RCTs comparing intralesional MMR vaccine and placebo were assessed. Meta-analysis showed a risk ratio of 0.24 [95% CI: 0.18, 0.34] favoring intralesional MMR vaccine and a highly significant difference in completely clearing target warts (P-value &lt;0.00001) versus placebo. Three of the 4 trials assessed response of distant warts showing a risk ratio of 0.28 [95% CI: 0.08, 0.96] and a significant difference (P=0.04) versus placebo. Pain and flu-like symptoms were the most common side effects with no recurrence seen after 3-6 months.&#x0D; Conclusions. Intralesional MMR vaccine significantly reduces and clears target and distant warts as compared to placebo. It is a generally safe intervention with lasting effect assessed up to 6 months follow-up.

Alopecia Totalis Treated with 1064 nm Picosecond Nd:YAG Laser: A Case Report

Alopecia areata (AA) is an autoimmune disorder causing nonscarring hair loss. Alopecia totalis (AT), the severe form of AA, is usually refractory to many first-line treatments including topical and intralesional corticosteroids and topical immunotherapy. Systemic corticosteroids, ultraviolet light phototherapy, and immunosuppressants may be effective but can cause side effects and high recurrence rates after discontinuing treatment. Janus kinase inhibitors and numerous types of lasers, such as 308 nm excimer laser or light, low-level laser therapy, and fractional lasers have been explored for alternative treatment of AA over the past few years with beneficial effects. Herein, we presented a case of AT treated with the novel 1064 nm picosecond Nd:YAG laser (ps-Nd:YAG) (Cutera, Brisbane, CA, USA) under a split-scalp study. A 25-year-old woman presenting with AT for two years was treated with topical and intralesional steroid and the 1064 nm Nd-YAG picosecond laser on the right half of the scalp. The laser treatment interval was once a month. The left half of the scalp was treated with topical and intralesional steroids alone. After treatment for six times, the right half of the scalp had greater improvement than the left half of the scalp. 1064 nm picosecond Nd:YAG laser therapy may be an effective alternative adjuvant treatment for AT.

Immunotherapy with PPD in treatment of warts: An open labelled study from western Uttar Pradesh

Immunotherapy with PPD in treatment of warts: An open labelled study from western Uttar Pradesh - IJCED- Print ISSN No: - 2581-4710 Online ISSN No:- 2581-4729 Article DOI No:- 10.18231/2581-4729.2019.0010, IP Indian Journal of Clinical and Experimental Dermatology-IP Indian J Clin Exp Dermatol

Bacillus Calmette-Guerin Immunotherapy for Recurrent Multiple Warts: An Open-Label Uncontrolled Study.

Background:Cutaneous warts present a therapeutic challenge because of recurrence and multiplicity and may become a frustrating condition for both patients and physicians. In the past few years, there has been an increase in intralesional immunotherapy for recurrent multiple warts not only because of its encouraging results in the treatment but also due to its ability to clear distant warts and preventing recurrence.Objective:The objective of this study was to evaluate the efficacy and safety of intralesional bacillus Calmette–Guerin (BCG) vaccine immunotherapy in the treatment of recurrent multiple warts.Materials and Methods:This study included 40 adult patients with multiple recurrent extragenital warts of different sizes, numbers, and duration, with or without distant warts. Patients were injected intralesionally with 0.1 ml BCG vaccine into the largest wart at a 3-week interval, directly without a pre-sensitization skin test, until complete clearance or for a maximum of three sessions. Follow-up was done every month for 3 months to detect any recurrence.Results:Out of the 40 patients enrolled in the study, 34 patients completed the treatment protocol of three injections and 3 months of follow-up and six patients discontinued for various reasons. Complete clearance of the lesions was achieved in 25 (73.53%) patients, partial clearance in 8 (23.53%) patients, and no response in 1 (2.94%) patient. Complete response was demonstrated in 75% of those presenting with distant warts. Therapy-related side effects were mild in the form of pain during injection, itching, erythema at the site of injection, and flu-like symptoms. None of the patients with complete response showed recurrence of lesions in a 3-month follow-up period.Conclusion:Intralesional BCG immunotherapy is a safe, effective, and promising treatment modality for recurrent multiple warts.

Intralesional Injection of the Measles-Mumps-Rubella Vaccine into Resistant Palmoplantar Warts: A Randomized Controlled Trial.

Common resistant-to-therapy warts pose a challenge to both clinicians and patients. Among many destructive and immunotherapeutic options, no single, fully effective treatment has been suggested yet. Many investigations, including those using intralesional antigen administrations, have demonstrated that cellular immunity plays a major role in the clearance of human papilloma virus (HPV) infection. The aim of the present study was to evaluate the effects of the intralesional injection of the measles-mumps-rubella (MMR) vaccine into resistant-to- treatment palmoplantar warts and its complications. In this single-blind, randomized, controlled clinical trial, 60 cases with resistant-to-therapy palmoplantar warts referring to the Dermatology Clinic of Bou-Ali Sina Hospital of Sari between June 2015 and 2016 were randomly assigned to 2 equal groups: the MMR Group received intralesional MMR and the Placebo Group was given saline injection. The injections were administered at 2-week intervals until complete clearance was achieved or for a maximum of 5 injections (<5 injections at 2-week intervals). The study protocol was registered in the Iranian Registry of Randomised Clinical Trials (ID: IRCT2016101027636N3), and the statistical analyses were performed using SPSS, version 17.0. The χ2 test and the F-test were used as appropriate, and a P value less than 0.05 was considered statistically significant. Complete clearance was observed in 65.2% (14⁄23) of the patients presenting with resistant-to-therapy palmoplantar warts in the MMR Group and 23.85% (5/21) in the Placebo Group (P=0.021). Recurrence was not observed in any of the completely cured patients at 6 months' follow-up. Intralesional immunotherapy with the MMR vaccine may result in a desirable therapeutic response and can be used as an effective and safe treatment option for palmoplantar warts, particularly persistent ones. Trial Registration Number: IRCT2016101027636N3.

The Efficacy and Safety of Intralesional Immunotherapy with Measles, Mumps, Rubella Virus Vaccine for the Treatment of Common Warts in Adults.

Background:Most therapeutic modalities for common warts remain unsatisfactory.Objectives:To evaluate efficacy and safety of intralesional MMR (measles, mumps, rubella virus) vaccine in the treatment of common warts in adults.Patients and Methods:There were 110 (M:F = 61:49) patients aged 19–62 years having 1–211 warts over dorsal hands, feet, palms, soles, and periungual skin for 1–252 months. MMR vaccine 0.25 mL was injected intralesionally in the largest wart and repeated at 2-week interval until complete clearance or maximum of five doses. The outcome was evaluated as complete clearance, excellent, good, or unsatisfactory response on visual analog scale at every visit and at 4 and 8 weeks, thereafter by comparing baseline clinical photograph. Likert scale was used for patient satisfaction level assessment similarly.Results:Only 51 patients completed the study and 42 (82.4%) of them showed complete clearance of warts and 9 (17.6%) patients showed good or unsatisfactory response. In 4 (7.8%) patients, the warts subsided completely after one dose itself. The four patients showing excellent response after five doses initially also continued to improve during follow-up period of 8 weeks. Except for injection site pain, no adverse effects were noted. There was no recurrence of warts among cured who were also very much satisfied from treatment.Conclusion:Despite variable results, intralesional MMR vaccine immunotherapy appears another possible safe and effective treatment option for common warts in a set of adult patients with advantages of regression of distant warts, no significant adverse effects and low recurrence. However, well-designed, controlled studies for minimum effective dose and treatment schedule are highly desirable to make any recommendation.

Evaluation of efficacy and safety of intralesional Measles-Mumps-Rubella virus vaccine for the treatment of common warts in children and adolescents

Background: No single treatment for warts has proven 100% efficacy and most therapeutic modalities remain unsatisfactory. Immunotherapy with Measles-Mumps-Rubella (MMR) vaccine remains underevaluated, especially in children. Objective: To evaluate the efficacy and safety of intralesional MMR vaccine in the treatment of common warts in children. Materials and Methods: Fifty-five (36 boys and 19 girls) children aged 5–18 (mean ± standard deviation 12.8 ± 3.88) years with common warts received 0.25 ml of MMR vaccine injected intralesionally in the largest wart. The dose was repeated at 2-week interval until complete clearance or for a maximum of 5 doses. Thereafter, they were followed up once a month for 24-week study period. The response was evaluated as complete clearance (complete disappearance of the wart(s) including distant ones and appearance of normal skin), partial clearance (≤99% reduction in size and number including distant ones and few residual warts still visible), good response (some reduction in size only including that of distant ones but no decrease in number of warts), or poor response (no change in size and number). Results: Only 46 patients completed the study and 27 (58.7%) of them had complete clearance of warts, 9 (19.6%) showed partial clearance and 10 (21.3%) patients showed no response. In 15 of 27 patients complete clearance was achieved after 5 doses, 7 had complete clearance after 4 doses and 2 patients each showed complete clearance after 2 and 3 doses, respectively. Conclusion: Intralesional MMR vaccine immunotherapy appears promising, effective, and safe treatment for common warts in children with the advantage of single-lesion infiltration, and resolution without scarring or pigmentary changes commonly seen with destructive therapies. However, better designed larger controlled studies are warranted.

Practical clinical guide on the use of talimogene laherparepvec monotherapy in patients with unresectable melanoma in Europe

Talimogene laherparepvec, a herpes simplex virus type 1-based intralesional oncolytic immunotherapy, is approved in Europe for the treatment of adults with unresectable stage IIIB-IVM1a melanoma, with no bone, brain, lung or other visceral disease. It has direct oncolytic effects in injected lesions, leading to the release of tumour-derived antigens and systemic immune effects mediated by the induction of anti-tumour immunity, which is enhanced by the production of granulocyte macrophage colony-stimulating factor. Responses (which occur in >40% of stage IIIB-IVM1a patients) are often durable (>50% last ≥6months) and occur in injected and uninjected lesions (in stage IIIB-IVM1c patients, 64%/34% of evaluable injected/uninjected non-visceral lesions, respectively, decreased in size by ≥50%). As with other immunotherapies, responses may be delayed or can arise after pseudoprogression. The pattern of treatment-emergent adverse events is distinct, being mostly grade 1/2, easy to manage, and rarely leading to treatment discontinuation. Systemic therapy represents the backbone of care for many metastatic melanoma patients. Nonetheless, the potential for durable locoregional control with a locally injected agent may make talimogene laherparepvec suitable for selected patients with stage IIIB/C disease, for whom surgery is not possible (e.g. with in-transit metastases, multiple melanoma lesions at different body sites, or those relapsing rapidly after repeated rounds of surgery) and slowly progressing disease. Here, we discuss which patients could be suitable for talimogene laherparepvec monotherapy based on the European indication, review the patterns/timing of response, and discuss the incidence/management of adverse events. Its potential use combined with immune checkpoint inhibitors is also discussed.

Treatment of periungual warts: comparison of topical 5% 5-fluorouracil and intralesional purified protein derivative in a South Indian teaching hospital

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Verrucae or warts are common skin lesions caused by the human papilloma virus. Treatment of warts, particularly those in the periungual region is usually difficult, exhibiting resistance. Available conventional treatment modalities offer little hope in curing periungual warts. Thus, there is a need for a simple, reliable, non-expensive treatment for periungual warts. Aim was to determine and compare the efficacy of intralesional immunotherapy using purified protein derivative (PPD) and topical 5-fluorouracil (5-FU) under tape occlusion for the treatment of periungual warts.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; In this prospective comparative study, Group 1 (PPD) patients, intralesional injection of PPD is given in a randomly selected lesion every 3 weeks for a maximum of six sittings. For Group 2 (topical 5% 5-FU under tape occlusion), patients are advised to apply 5% 5-FU under occlusion on the lesion(s) selected for study during the night and left for 12 hours. This is done for 3 months. After completion of the treatment and after the declaration of the cure – follow-up is done for the next three months to look for recurrence.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Intralesional PPD had a significantly higher cure rate (88%) than that of topical 5-fluorouracil under occlusion (20%). The mean time taken for the resolution of the periungual warts was 6.6 weeks for intralesional PPD compared to 9.8 weeks for topical 5-fu under tape occlusion.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; The cure rate of intralesional PPD group (88%) was much higher than that of topical 5% 5-fluorouracil under tape occlusion group (20%). In the PPD group, the younger patients responded well and faster. There was no difference in cure rate among age groups in 5 FU group.&lt;/p&gt;

Intralesional immunotherapy for the treatment of warts: A network meta-analysis

Without clear evidence, selecting among the existing immunotherapeutic options for warts remains challenging. Through network meta-analyses, we aimed to evaluate the comparative efficacy of different intralesional immunotherapeutic modalities. We included randomized controlled trials comparing intralesional immunotherapeutic modalities to cryotherapy, placebo, or imiquimod. All outcomes were presented as odds ratios (ORs) with 95% confidence intervals. Both conventional and network meta-analyses (with a frequentist approach) were conducted on R software. The P-score was used to rank different treatments. Network meta-analysis of 17 randomized controlled trials (1676 patients) showed that PPD (purified protein derivative vaccine, OR 39.56), MMR (measles, mumps, rubella vaccine, OR 17.46) and interferon β (OR 15.55) had the highest efficacy in terms of complete recovery at the primary site compared with placebo. Regarding complete recovery at the distant site, autoinoculation (OR 79.95), PPD (OR 42.95), and MMR (OR 15.39) were all statistically superior to placebo. According to the P-score, MMR was more effective than other modalities in reducing the recurrence rate at the same site. Relatively small sample size in some comparisons and variability in baseline characteristics. PPD and MMR were the most effective in achieving complete primary and distant recovery (along with autoinoculation for distant recovery) and reducing the recurrence rate at the same site compared with cryotherapy and other immunotherapeutic modalities.

A phase 1b/2, multicenter, open-label trial to evaluate the safety of talimogene laherparepvec (T-VEC) injected into primary and metastatic liver tumors alone and in combination with pembrolizumab (pembro) (MASTERKEY-318).

TPS3105Background: Combining the intralesional oncolytic immunotherapy T-VEC with systemic immunotherapy may enhance the systemic efficacy of both agents through complementary mechanisms of action....

A comparative study between intralesional PPD and vitamin D3 in treatment of viral warts

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Viral warts are caused by human papillomavirus. There are innumerable treatment modalities but they may result in partial clearance or recurrence. Some newer and effective treatments include intralesional immunotherapy. We undertook a study to evaluate the safety and efficacy of two such immunotherapy namely tuberculin purified protein derivative (PPD) versus intralesional vitamin D3 for the treatment of viral warts.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; A total of 80 patients were included in the study. Group 1 patient were injected with 10 TU of tuberculin PPD (0.1 ml) intralesional while in group 2 patients were injected (0.5 ml) vitamin D3. The clinical assessment was done by photographic measurements at baseline, before each treatment session, and after the completion of treatment.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; In group 1 A total of 80% (32 patients) showed complete clearance and 20% (8 patients) showed partial response while in group 2 72.5% (29 patients) showed complete clearance while 27.5% (11 patients) showed partial response. No significant side effects were observed except for pain at the site of injection.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Intralesional vitamin D and intralesional Tuberculin PPD immunotherapy shows significant results in treatment of viral warts.&lt;/p&gt;

A Randomized double Blind Controlled Study Comparing the Efficacy of Intralesional MMR Vaccine with Normal Saline in the Treatment of Cutaneous Warts.

Background:Recently, with better understanding of the immunology of warts, immunotherapeutic approaches have emerged as an effective treatment option for the management of cutaneous warts. Intralesional immunotherapy with MMR vaccine is one such modality but there are still lack of enough placebo-controlled studies.Aim:To evaluate the efficacy of intralesional MMR in patients of extragenital warts in a double-blinded manner using normal saline as control.Patients and Methods:One hundred patients of extragenital cutaneous warts were randomly allocated into two groups, the interventional (MMR) group and control (normal saline) group. MMR vaccine was injected intralesionally in the patients belonging to interventional group, a similar volume of normal saline (NS) was injected in the control group. The outcome in terms of treatment response, adverse effects, and recurrences were evaluated and compared.Results:Eighteen of thirty (60%) patients in the interventional group achieved complete response as against 7 (23.3%) in the control group (P = 0.01). Distant warts cleared in 69.5% patients in the interventional groupcompared to none in the control group. Adverse effects seen in both groups were injection site pain and mild erythema. A total of 57.1% patients showed recurrences in the control group compared to 16.6% in the interventional group.Conclusion:Intralesional MMR vaccine is an effective treatment option in patients with multiple extragenital warts. It is suggested that it should be used as first-line therapy for multiple warts and a second-line therapy for warts recalcitrant to standard therapies.