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

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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Treatment beyond progression with immune checkpoint inhibitors in advanced melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21541 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21541-e21541

Author(s):

Pawel Sobczuk ◽

Anna Malgorzata Czarnecka ◽

Mateusz Spalek ◽

Pawel Teterycz ◽

Monika Dudzisz-Śledź ◽

...

Keyword(s):

Multimodal Treatment ◽

Multidisciplinary Treatment ◽

Objective Response ◽

Real Life ◽

Tumor Burden ◽

Advanced Melanoma ◽

Disease Stage ◽

Treatment Beyond Progression ◽

Melanoma Patients ◽

Metastatic Sites

e21541 Background: Immunotherapy (ITH) holds the possibility of tumor burden decrease after initial RECIST defined progression (PD). Clinical concept of treating of selected patients (pts) beyond PD is supported by this pseudoprogression phenomenon. The aim of this study was to evaluate real-life practice and outcomes related to treatment beyond progression (TBP) in melanoma patients. Methods: We evaluated advanced melanoma pts who started anti-PD1 treatment between 12/2015 and 12/2018 and identified pts who received TBP and had subsequent imaging to evaluate the tumor burden. Survival analyses were performed using the Kaplan-Meier method, Log-rank, chi-square and Fisher exact tests were used for comparison between groups. Data cut-off was 02/2021. Results: Of 399 subsequent melanoma pts treated, 57 (14%) patients received TBP. Anti-PD1 was 1st line treatment in 61.4% and 2nd line - in 38.6% of patients. 71.9% patients were diagnosed with skin, 7.0% - mucosal and 21.1% with FPI melanoma and 47.4% were BRAF mutated, 56.1% were male and 12.3% had 3 or more metastatic sites at treatment initiation. In this cohort median time to 1st PD (TTFP) was 4.43 months(m), while to 2nd PD (TTSP) – 8.01 m. On TBP 26.3% pts achieved objective response (OR), and next 42.1% - SD. 1st PD was reported most often as increase in 3 or more targets or one new lesion – both 22.8%; and in 24.6% cases involved central nervous system. In 56.8% second PD was observed in the same targets as 1st PD. 61.4% patients received multimodal treatment of ITH combined with radiation therapy – in 49.1%, surgery - 5.3% and both - 7.0%. There was no correlation of TTSP with gender, ECOG, initial disease stage or TNM, BRAF mutation, number of metastatic sites or pattern of progression. Multimodal treatment resulted in 13.6 m TTSP, while ITH alone - 8.0 m (p = 0.056). 1st line OR correlated with DCR on TBP while TTFP > 6 m correlated with TTSP (HR = 0.53, 95%CI 0.28-0.99). Patients with 1st line CR – had median TTSP 16.4 m, with PR – 23.5 m, while those with PD – 5.1 m. Median OS after 1st PD was 26 months and correlated with OR on TBP. Conclusions: Selected clinically fit melanoma patients despite evidence of first radiographic progression may benefit from continued treatment with PD-1 inhibitors. Multidisciplinary treatment should be offered to these patients including radiosurgery or stereotactic radiotherapy of progressing loci. Molecular biomarkers of TTSP should be analyzed in prospective studies.

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Talimogene laherparepvec treatment to overcome loco-regional acquired resistance to immune checkpoint blockade in tumor stage IIIB–IV M1c melanoma patients

Cancer Immunology Immunotherapy ◽

10.1007/s00262-020-02487-x ◽

2020 ◽

Vol 69 (5) ◽

pp. 759-769 ◽

Cited By ~ 1

Author(s):

Anne Fröhlich ◽

Dennis Niebel ◽

Simon Fietz ◽

Eva Egger ◽

Andrea Buchner ◽

...

Keyword(s):

Immune Checkpoint ◽

Acquired Resistance ◽

Tumor Stage ◽

Immune Checkpoint Blockade ◽

Checkpoint Blockade ◽

Stage Iiib ◽

Talimogene Laherparepvec ◽

Melanoma Patients

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Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study

Journal for ImmunoTherapy of Cancer ◽

10.1186/s40425-016-0116-2 ◽

2016 ◽

Vol 4 (1) ◽

Cited By ~ 51

Author(s):

Howard L. Kaufman ◽

Thomas Amatruda ◽

Tony Reid ◽

Rene Gonzalez ◽

John Glaspy ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Study ◽

Talimogene Laherparepvec ◽

Local Responses ◽

Melanoma Patients

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Clinical Categorization Algorithm (CLICAL) and Machine Learning Approach (SRF-CLICAL) to Predict Clinical Benefit to Immunotherapy in Metastatic Melanoma Patients: Real-World Evidence from the Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy

Cancers ◽

10.3390/cancers13164164 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4164

Author(s):

Gabriele Madonna ◽

Giuseppe V. Masucci ◽

Mariaelena Capone ◽

Domenico Mallardo ◽

Antonio Maria Grimaldi ◽

...

Keyword(s):

Machine Learning ◽

Metastatic Melanoma ◽

Learning Algorithm ◽

Checkpoint Inhibitors ◽

Real Life ◽

Previous Treatment ◽

Clinical Decision ◽

Neutrophil Lymphocyte Ratio ◽

Real World Evidence ◽

Melanoma Patients

The real-life application of immune checkpoint inhibitors (ICIs) may yield different outcomes compared to the benefit presented in clinical trials. For this reason, there is a need to define the group of patients that may benefit from treatment. We retrospectively investigated 578 metastatic melanoma patients treated with ICIs at the Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale” of Napoli, Italy (INT-NA). To compare patients’ clinical variables (i.e., age, lactate dehydrogenase (LDH), neutrophil–lymphocyte ratio (NLR), eosinophil, BRAF status, previous treatment) and their predictive and prognostic power in a comprehensive, non-hierarchical manner, a clinical categorization algorithm (CLICAL) was defined and validated by the application of a machine learning algorithm—survival random forest (SRF-CLICAL). The comprehensive analysis of the clinical parameters by log risk-based algorithms resulted in predictive signatures that could identify groups of patients with great benefit or not, regardless of the ICI received. From a real-life retrospective analysis of metastatic melanoma patients, we generated and validated an algorithm based on machine learning that could assist with the clinical decision of whether or not to apply ICI therapy by defining five signatures of predictability with 95% accuracy.

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Distinguishing melanophages from tumor in melanoma patients treated with talimogene laherparepvec

Melanoma Research ◽

10.1097/cmr.0000000000000661 ◽

2020 ◽

Vol Publish Ahead of Print ◽

Author(s):

Claire Audrey-Bayan ◽

Megan H. Trager ◽

Robyn D. Gartrell-Corrado ◽

Emanuelle M. Rizk ◽

Jaya Pradhan ◽

...

Keyword(s):

Talimogene Laherparepvec ◽

Melanoma Patients

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Real World Outcomes of Ipilimumab and Nivolumab in Patients with Metastatic Melanoma

Cancers ◽

10.3390/cancers12082329 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2329

Author(s):

Nethanel Asher ◽

Guy Ben-Betzalel ◽

Shaked Lev-Ari ◽

Ronnie Shapira-Frommer ◽

Yael Steinberg-Silman ◽

...

Keyword(s):

Adverse Events ◽

Metastatic Melanoma ◽

Real World ◽

Real Life ◽

Response Rates ◽

Immune Checkpoints ◽

World Population ◽

Induction Phase ◽

Treatment Naïve ◽

Melanoma Patients

Background: Immunotherapy has drastically changed the outlook for melanoma patients over the past decade. Specifically, the dual blockade of immune checkpoints using ipilimumab and nivolumab has shown unprecedented response rates and survival outcomes. This immense achievement, though, is at the cost of toxicity, with 60% of the patients experiencing high-grade adverse events (AEs). Our study aims to report the efficacy and toxicity outcomes of an out-of-trial, real-life population. Methods: Data on metastatic melanoma patients treated with ipilimumab and nivolumab were retrieved from our melanoma database—a single-center prospectively updated, medical-records based oncologic registry. Data included demographics, clinical and pathological information, as well as tumor responses and survival. Associations between patient or treatment characteristics and outcomes were also evaluated. Results: We identified 172 metastatic melanoma patients, of whom 64% were treatment-naïve. The median follow-up was 12 months. The response rates for treatment-naïve and previously-treated patients were 61% and 25%, respectively; median progression-free survival (PFS) were 12.2 and 2.6 months, and median overall survival (OS) were not-reached (NR) and 6.1 months, respectively. The estimated three-year OS for treatment-naïve patients was 58% (95% CI 42–65). At data cutoff, 22% were still on-treatment. Grade 3–4 adverse events (AEs) were reported in 60% of the patients, almost all of whom were exposed to steroid treatments (59%); AEs were fatal in 4 patients, and led to permanent treatment discontinuation in 31%. Factors significantly associated with outcome were cutaneous histology, low lactate dehydrogenase (LDH), low number of metastatic sites, performance status, first line of treatment and number of combinations administered during the induction phase. Conclusions: Despite the profoundly different baseline patient characteristics, the combination of ipilimumab and nivolumab is as effective in the real-world population as it was in clinical trials, including long-term outcomes. In addition to confirming the significance of baseline prognostic factors, our study reveals that the number of combinations effectively administered may also be correlated with good outcome.

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