Complete Response of Advanced Melanoma Treated With Talimogene Laherparepvec and Subsequent Sweet’s-like Infiltrate

Aim: Talimogene laherparepvec (T-VEC) is a genetically modified oncolytic herpesvirus approved for the treatment of unresectable, locoregionally advanced and recurrent melanoma. There is little relevant literature in the context of retreatment with T-VEC. Materials & methods: We reviewed four patients aged 71–87 years old with stage IIIB–IV melanoma at treatment who were rechallenged with T-VEC after experiencing recurrence of locoregional disease or prior treatment-limiting toxicity. Results: Cessation of initial treatment was due to one of the following reasons: severe adverse event (one case), mixed response (one case) or complete response (two cases). Three males and one female underwent T-VEC retreatment with a mean of 5.5 injection cycles. Three patients experienced a complete response to retreatment, while one experienced disease progression. Conclusion: Intralesional T-VEC may be effective and well-tolerated in patients who have completed prior T-VEC therapy.

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Talimogene laherparepvec (T‐ VEC ) in advanced melanoma: complete response in a heart and kidney transplant patient. A case report

British Journal of Dermatology ◽

10.1111/bjd.17783 ◽

2019 ◽

Vol 181 (1) ◽

pp. 186-189 ◽

Cited By ~ 6

Author(s):

J. Ressler ◽

R. Silmbrod ◽

A. Stepan ◽

F. Tuchmann ◽

A. Cicha ◽

...

Keyword(s):

Case Report ◽

Kidney Transplant ◽

Transplant Patient ◽

Complete Response ◽

Advanced Melanoma ◽

Kidney Transplant Patient ◽

Talimogene Laherparepvec

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Real-life use of talimogene laherparepvec (T-VEC) in melanoma patients in centers in Austria, Switzerland and Germany

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001701 ◽

2021 ◽

Vol 9 (2) ◽

pp. e001701

Author(s):

Julia Maria Ressler ◽

Matthias Karasek ◽

Lukas Koch ◽

Rita Silmbrod ◽

Joanna Mangana ◽

...

Keyword(s):

Chart Review ◽

Progressive Disease ◽

Overall Response Rate ◽

Real Life ◽

Retrospective Chart Review ◽

Distant Metastases ◽

Complete Response ◽

Talimogene Laherparepvec ◽

Metastatic Lesions ◽

Melanoma Patients

BackgroundTalimogene laherparepvec (T-VEC) is a licensed therapy for use in melanoma patients of stage IIIB-IVM1a with injectable, unresectable metastatic lesions in Europe. Approval was based on the Oncovex Pivotal Trial in Melanoma study, which also included patients with distant metastases and demonstrated an overall response rate (ORR) of 40.5% and a complete response (CR) rate of 16.6%.ObjectivesThe aim of this study was to assess the outcome of melanoma patients treated with T-VEC in a real-life clinical setting.MethodsBased on data from 10 melanoma centers in Austria, Switzerland and southern Germany, we conducted a retrospective chart review, which included 88 patients (44 male, 44 female) with a median age of 72 years (range 36–95 years) treated with T-VEC during the period from May 2016 to January 2020.Results88 patients fulfilled the inclusion criteria for analysis. The ORR was 63.7%. 38 patients (43.2%) showed a CR, 18 (20.5%) had a partial response, 8 (9.1%) had stable disease and 24 (27.3%) patients had a progressive disease. The median treatment period was 19 weeks (range: 1–65), an average of 11 doses (range: 1–36) were applied. 39 (45.3%) patients developed adverse events, mostly mild, grade I (64.1%).ConclusionThis real-life cohort treatment with T-VEC showed a high ORR and a large number of durable CRs.

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Phase II trial of the IDO pathway inhibitor indoximod plus pembrolizumab for the treatment of patients with advanced melanoma

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-002057 ◽

2021 ◽

Vol 9 (6) ◽

pp. e002057

Author(s):

Yousef Zakharia ◽

Robert R McWilliams ◽

Olivier Rixe ◽

Joseph Drabick ◽

Montaser F Shaheen ◽

...

Keyword(s):

Phase Ii ◽

Single Agent ◽

Objective Response ◽

Progression Free Survival ◽

Standard Of Care ◽

Complete Response ◽

Advanced Melanoma ◽

Free Survival ◽

Programmed Death ◽

Evaluable Population

BackgroundThe indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) that result from IDO activity. In this study, indoximod was used in combination with a checkpoint inhibitor (CPI) pembrolizumab for the treatment for advanced melanoma.MethodsPatients with advanced melanoma were enrolled in a single-arm phase II clinical trial evaluating the addition of indoximod to standard of care CPI approved for melanoma. Investigators administered their choice of CPI including pembrolizumab (P), nivolumab (N), or ipilimumab (I). Indoximod was administered continuously (1200 mg orally two times per day), with concurrent CPI dosed per US Food and Drug Administration (FDA)-approved label.ResultsBetween July 2014 and July 2017, 131 patients were enrolled. (P) was used more frequently (n=114, 87%) per investigator’s choice. The efficacy evaluable population consisted of 89 patients from the phase II cohort with non-ocular melanoma who received indoximod combined with (P).The objective response rate (ORR) for the evaluable population was 51% with confirmed complete response of 20% and disease control rate of 70%. Median progression-free survival was 12.4 months (95% CI 6.4 to 24.9). The ORR for Programmed Death-Ligand 1 (PD-L1)-positive patients was 70% compared with 46% for PD-L1-negative patients. The combination was well tolerated, and side effects were similar to what was expected from single agent (P).ConclusionIn this study, the combination of indoximod and (P) was well tolerated and showed antitumor efficacy that is worth further evaluation in selected patients with advanced melanoma.

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Induced Vitiligo due to Talimogene Laherparepvec Injection for Metastatic Melanoma Associated with Long-term Complete Response

Acta Dermato Venereologica ◽

10.2340/00015555-3061 ◽

2019 ◽

Vol 99 (2) ◽

pp. 232-233 ◽

Cited By ~ 3

Author(s):

P Iglesias ◽

S Ribero ◽

A Barreiro ◽

S Podlipnik ◽

C Carrera ◽

...

Keyword(s):

Metastatic Melanoma ◽

Complete Response ◽

Talimogene Laherparepvec

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Clinical and Immune Responses in Advanced Melanoma Patients Immunized With an Anti-Idiotype Antibody Mimicking Disialoganglioside GD2

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.2.376 ◽

2000 ◽

Vol 18 (2) ◽

pp. 376-376 ◽

Cited By ~ 92

Author(s):

Kenneth A. Foon ◽

Jose Lutzky ◽

Rathindra N. Baral ◽

John R. Yannelli ◽

Laura Hutchins ◽

...

Keyword(s):

Soft Tissue ◽

Immune Responses ◽

Disease Progression ◽

San Francisco ◽

Median Survival ◽

Complete Response ◽

Advanced Melanoma ◽

Visceral Metastasis ◽

Prior Therapy ◽

Kaplan Meier

PURPOSE: To determine immune responses and toxicity to the anti-idiotype vaccine, as well as clinical responses and survival, we initiated a clinical trial for patients with advanced melanoma treated with an anti-idiotype antibody (TriGem) that mimics the disialoganglioside GD2. PATIENTS AND METHODS: Forty-seven patients with advanced melanoma received either 1-, 2-, 4-, or 8-mg doses of TriGem (Titan Pharmaceuticals Inc, South San Francisco, CA) mixed with QS-21 adjuvant (Aquila Biopharmaceuticals, Inc, Worcester, MA) 100 μg subcutaneously weekly for 4 weeks and then monthly until disease progression. Median age was 57 years, there were 32 men and 15 women, 43% of patients had undergone prior therapy for metastatic disease, 55% had disease confined to soft tissue, and 45% had visceral metastasis. RESULTS: Hyperimmune sera from 40 of 47 patients showed an anti–anti-idiotype (Ab3) response. Patient Ab3 was truly Ab1′ because it specifically bound purified disialoganglioside GD2. The isotypic specificity of the Ab3 antibody consisted of predominantly immunoglobulin (Ig)G, and all IgG subclasses were represented. One patient had a complete response that persisted at 24 months, and 12 patients were stable from 14+ to 37+ months (median, 18+ months). Disease progression occurred in 32 patients on study from 1 to 17 months (median, 5.5 months), and 21 have died at 1 to 16 months (median, 6 months). The Kaplan-Meier–derived overall median survival has not been reached. Median survival has not been reached for the 26 patients with soft tissue disease only and was 13 months for 21 patients with visceral metastasis. Toxicity consisted of local reaction at the site of injection and mild fever and chills. CONCLUSION: TriGem has minimal toxicity and generates robust and specific IgG immune responses against GD2. Objective responses were minimal, but there may be a favorable impact on disease progression and survival that will require prospective randomized trials.

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High-dose interleukin-2 (HD IL-2) in the treatment of advanced melanoma: The University of Pittsburgh experience.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.9075 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 9075-9075

Author(s):

Diwakar Davar ◽

Melissa Saul ◽

Ahmad A. Tarhini ◽

An Tran ◽

Kerry Trent ◽

...

Keyword(s):

Proportional Hazards ◽

Interleukin 2 ◽

Complete Response ◽

Median Number ◽

Cox Proportional Hazards ◽

Advanced Melanoma ◽

High Dose ◽

Severe Toxicity ◽

University Of Pittsburgh ◽

Radiological Data

9075 Background: IL-2 is a T-cell growth factor tested in a variety of regimens for advanced melanoma (MEL) and renal cell carcinoma (RCC). High-dose IL-2 (600,000-720,000 IU/kg administered intravenously every 8 hours for up to 14 consecutive doses) was approved by FDA for advanced MEL and RCC in 1998 based upon the durability of responses observed. Early studies of HD IL-2 reported overall (OR) and complete response (CR) rates of 16% and 8% respectively. Severe toxicity limited use to specialized centers with standardized protocols, either intensive care (ICU) or oncology specialty settings. The U Pittsburgh has treated 1022 patients with IL-2 at any dosage and we here present outcomes of 550 MEL pts treated with HD IL-2 in an oncology specialty non-ICU setting. Methods: Clinical and radiological data were collected on all pts treated with IL-2 using the UPCI Cancer Registry and Medical Archival System (MARS). Pharmacy records were reviewed for dosing details. The influence of baseline characteristics on treatment outcomes was assessed using Cox proportional hazards analysis. Results: A total of 848 pts received HD IL-2, of which 298 pts had RCC while 550 had MEL. Detailed pharmacy dosing records were reviewed from 176 pts treated over the past 12 years (2000-2012) who received a total of 3738 cycles. Of 165 pts evaluable for response, OR was documented in 24 pts (14.8%) and CR in 5 pts (3.0%). Median overall survival (OS) was 10.0 mos for all patients and 21.5 mos for responders (CR+PR). Median number of doses per cycle was 7. Toxicity was consistent with prior reports. HD IL-2 required ICU transfers in 5% and 1 death was attributed to HD IL-2. Pts with higher baseline lactate dehydrogenase (LDH) had poorer OS (p < 0.05). Conclusions: In this large and uniformly treated series of recent patients treated with IL-2 OR/CR rates with HD IL-2 are 14.8% and 3.0% respectively. Higher LDH is associated with poorer outcome. Biomarkers of response are currently being evaluated in banked clinical specimens collected from patients under the SPORE in Skin Cancer (P50 CA121973).

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