scholarly journals Observational study of talimogene laherparepvec use in the anti-PD-1 era for melanoma in the US (COSMUS-2)

2020 ◽  
Vol 7 (2) ◽  
pp. MMT41
Author(s):  
James Sun ◽  
Brian R Gastman ◽  
Lucy McCahon ◽  
Elizabeth I Buchbinder ◽  
Igor Puzanov ◽  
...  
Keyword(s):  
Observational Study ◽  
Metastatic Melanoma ◽  
Real World ◽  
Retrospective Review ◽  
Progressive Disease ◽  
Talimogene Laherparepvec ◽  
Intralesional Therapy ◽  
The Us ◽  
Melanoma Patients

Aim: Talimogene laherparepvec (T-VEC) is an intralesional therapy for unresectable, metastatic melanoma. T-VEC real-world use in the context of anti-PD1-based therapy requires further characterization. Materials & methods: A retrospective review of T-VEC use from 1 January 2017 and 31 March 2018 for melanoma patients was conducted at seven US institutions. Results: Among 83 patients, three categories of T-VEC and anti-PD-1 therapy were identified: T-VEC used without anti-PD-1 (n = 29, 35%), T-VEC after anti-PD-1-based therapy (n = 22, 27%) and concurrent T-VEC and anti-PD-1-based therapy (n = 32, 39%). 25% of patients discontinued T-VEC therapy due to no remaining injectable lesions, 37% discontinued T-VEC due to progressive disease. Discontinuation of T-VEC did not differ by anti-PD-1-based therapy use or timing. Conclusion: In real-world settings, T-VEC may be used concurrently with or after anti-PD-1-based therapy.

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

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.

scholarly journals Prospective Molecular Profiling of Circulating Tumor Cells from Patients with Melanoma Receiving Combinatorial Immunotherapy

2019 ◽  
Vol 66 (1) ◽  
pp. 169-177 ◽  
Author(s):  
Selena Y Lin ◽  
Shu-Ching Chang ◽  
Stella Lam ◽  
Romela Irene Ramos ◽  
Kevin Tran ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Tumor Cells ◽  
Clinical Outcomes ◽  
Circulating Tumor Cells ◽  
Progressive Disease ◽  
Molecular Profiling ◽  
Braf V600e ◽  
Blood Samples ◽  
Mrna Profiling ◽  
Melanoma Patients

Abstract BACKGROUND Blood molecular profiling of circulating tumor cells (CTCs) can enable monitoring of patients with metastatic melanoma during checkpoint inhibitor immunotherapy (CII) and in combination with targeted therapies. We developed a microfluidics-based CTC platform to explore CTC profiling utility in CII-treated patients with melanoma using a melanoma messenger RNA (mRNA)/DNA biomarker panel. METHODS Blood samples (n = 213) were collected prospectively from 75 American Joint Committee on Cancer-staged III/IV melanoma patients during CII treatment and those enriched for CTCs. CTC profiling was performed using 5 known melanoma mRNA biomarkers and BRAF V600E DNA mutation. CTC biomarker status associations with clinical outcomes were assessed. RESULTS CTCs were detected in 88% of blood samples from patients with melanoma. CTC-derived biomarkers and clinical variables analyzed using classification and regression tree analysis revealed that a combination of lactate dehydrogenase, CTC-mRNA biomarkers, and tumor BRAF–mutation status was indicative of clinical outcomes for patients with stage IV melanoma (n = 52). The panel stratified low-risk and high-risk patients, whereby the latter had poor disease-free (P = 0.03) and overall survival (P = 0.02). Incorporation of a DNA biomarker with mRNA profiling increased overall CTC-detection capability by 57% compared to mRNA profiling only. RNA sequencing of isolated CTCs identified significant catenin beta 1 (CTNNB1) overexpression (P <0.01) compared to nondisease donor blood. CTC-CTNNB1 was associated with progressive disease/stable disease compared to complete-responder patient status (P = 0.02). Serial CTC profiling identified subclinical disease in patients who developed progressive disease during treatment/follow-up. CONCLUSIONS CTC-derived mRNA/DNA biomarkers have utility for monitoring CII, targeted, and combinatorial therapies in metastatic melanoma patients.

Serum 5-s-cysteinyldopa for identifying non-responders to nivolumab treatment of melanoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21068-e21068
Author(s):  
Toshikazu Omodaka ◽  
Akane Minagawa ◽  
Hisashi Uhara ◽  
Kazumasa Wakamatsu ◽  
Tomonobu Koizumi ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Progressive Disease ◽  
University Hospital ◽  
Normal Range ◽  
Treatment Progress ◽  
Maximum Change ◽  
Imaging Examination ◽  
Melanoma Patients ◽  
Monitor Treatment Response ◽  
Sensitive Marker

e21068 Background: Despite considerable advances in the treatment of metastatic melanoma, reliable markers to monitor treatment response are still lacking. 5-S-cysteinyldopa (5-S-CD) is a precursor of melanin that has been established as a biomarker for melanoma progression. This study evaluated serum 5-S-CD in parallel with lactate dehydrogenase (LD) as a predictor of treatment progress in melanoma patients receiving Nivolumab (Nivo) therapy. Materials and Methods: Twenty-one patients (median age: 77 years; 10 male and 11 female) with metastatic melanoma who were treated with Nivo at Shinshu University Hospital between 2014 and 2016 were retrospectively examined. Primary lesions were in the head and neck in 5 patients, trunk and extremities in 5 patients, acral area in 5 patients, mucosa in 3 patients, and an unknown site in 3 patients. Serum 5-S-CD and LD were recorded and change ratios were calculated between the baseline and values obtained 14-90 days after the initial administration of Nivo, prior to the first imaging examination. The change ratios of each biomarker were evaluated based on the response classifications defined by the RECIST criteria (version 1.1). Results: The respective baseline median concentrations of serum 5-S-CD (normal range: 2.5–6.1 nmol/L) and LD (normal range: 120–230 IU/L) were 26.5 nmol/L and 247 IU/L in partial response (PR) patients (n = 5), 74.2 nmol/L and 428 IU/L in a stable disease (SD) patient (n = 1), and 9.9 nmol/L and 237 IU/L in progressive disease (PD) patients (n = 15). The maximum change ratios of 5-S-CD before the first imaging examination were 0.13–1.14 (median: 0.34) in PR patients and 0.30–15.38 (1.52) in PD patients, as compared with 0.73–0.98 (0.96) in PR patients and 0.63–2.23 (1.04) in PD patients for LD. The maximum change ratios of 5-S-CD were ≥1.3 in 9 of 15 (60%) PD patients but < 1.3 in all (100%) PR and SD patients. Conclusions: The maximum change ratio of serum 5-S-CD in the early phase of Nivo treatment may be a useful and more sensitive marker than that of LD to predict a non-response in metastatic melanoma.

Humanistic burden of disease in earlier stage metastatic (stage IIIb/c-IVM1a) versus late stage metastatic (IVM1b/c) melanoma patients in a real-world setting in the U.S.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9561-9561
Author(s):  
Jacqueline Buchanan ◽  
Swaminathan Murugappan ◽  
Rebecca Moon ◽  
Adam Roughley ◽  
Alex Rider
Keyword(s):  
Metastatic Melanoma ◽  
Real World ◽  
Late Stage ◽  
Well Being ◽  
Primary Diagnosis ◽  
Cross Sectional Survey ◽  
Health States ◽  
Cross Sectional ◽  
Caregiver Support ◽  
Melanoma Patients

9561 Background: To assess melanoma specific health-related quality of life (HRQoL) and health states in patients with earlier stage metastatic (IIIb/c-IVM1a) versus late stage metastatic (IVM1b/c) melanoma. Methods: Data were collected from the Adelphi Real World Advanced Melanoma Disease-Specific Programme, a cross-sectional survey of 112 physicians and their patients (N = 666). Data were collected between March and July 2016 in the US. A subset of 183 patients completed the Functional Assessment of Cancer Therapy Melanoma (FACT-M) and EuroQol-5D (EQ-5D) one time. Patients were classified by stage of melanoma at time of consultation. Descriptive analyses of HRQoL scores between earlier and late stage metastatic melanoma were assessed using Mann-Whitney U tests. Results: The mean age of the earlier stage and late stage metastatic patients was 62 and 64 respectively. More earlier stage metastatic patients had an ECOG status of 0 or 1 versus late stage metastatic patients (85%, 75% respectively). A total of 31% of late stage metastatic patients required caregiver support and had a median time since primary diagnosis of 5.0 months whereas earlier stage metastatic patients reported 14% and 5.2 months respectively. Patients with earlier stage metastatic melanoma had better mean EQ-5D index scores versus late stage metastatic melanoma patients (0.81 (n = 84), 0.76 (n = 93); p = 0.0103). Higher scores indicating better HRQoL were observed between earlier stage metastatic versus late stage metastatic melanoma patients for the FACT-M (120.7 (n = 81), 107.4 (n = 91); p = 0.0017) and subscales (except Social Well Being). Clinically meaningful differences between groups using published minimal important differences (MIDs) were observed in in 6/7 FACT-M subscales and EQ-5D VAS. Conclusions: Differences in HRQoL and health states were observed between earlier stage metastatic and late stage metastatic melanoma populations, highlighting the detrimental effect of developing metastatic disease. These results suggest that treatments that delay progression of the disease are important to conserve patients HRQoL

Talimogene laherparepvec with systemic immunotherapy in melanoma: A real-world experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21549-e21549
Author(s):  
Tapas Ranjan Behera ◽  
Yanwen Chen ◽  
Jung Min Song ◽  
Steve Shih-lin Huang ◽  
Pauline Funchain ◽  
...  
Keyword(s):  
Overall Survival ◽  
Metastatic Melanoma ◽  
Real World ◽  
Response Rate ◽  
Local Response ◽  
Single Institution ◽  
Talimogene Laherparepvec ◽  
Metastatic Lesions ◽  
Systemic Immunotherapy

e21549 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%, 95% CI 0.651-0.9730. Progression free survival at 1-year in the monotherapy group was 71.6%, 95% CI 0.557-0.918. 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.

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

Cancers ◽  
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.

Vemurafenib in BRAF-mutant metastatic melanoma patients in real-world clinical practice

2018 ◽  
pp. 1 ◽  
Author(s):  
Maartje G. Schouwenburg ◽  
Anouk Jochems ◽  
Brenda Leeneman ◽  
Margreet G. Franken ◽  
Alfons J.M. van den Eertwegh ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Metastatic Melanoma ◽  
Real World ◽  
Melanoma Patients ◽  
Braf Mutant

The efficacy and safety analysis of PD-1 inhibitor combined with interferon-α1b: A real-world study in Chinese metastatic melanoma patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21507-e21507
Author(s):  
Guannan Zhu ◽  
Qiong Shi ◽  
Chunying Li ◽  
Tianwen Gao
Keyword(s):  
Combination Therapy ◽  
Metastatic Melanoma ◽  
Real World ◽  
Performance Status ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Efficacy And Safety ◽  
Ecog Performance Status ◽  
Melanoma Patients ◽  
Grade 3

e21507 Background: Clinical data on PD-1 inhibitor combined with interferon in metastatic melanoma treatment were still limited. The objective of this study was to assess the efficacy and safety of PD-1 inhibitor/interferon-α1b combination therapy for Chinese metastatic melanoma patients in the real world. Methods: We reviewed patients diagnosed as metastatic melanoma and had received PD-1 inhibitor (pembrolizumab, 2 mg/kg, every 3 weeks, intravenously or toripalimab 240mg every 2 weeks, intravenously) combined with interferon-α1b(10μg/kg, every other day, subcutaneously) in Xijing Hospital from Dec 2018 to Nov 2020. Efficacy and safety profiles were evaluated using Response Evaluation Criteria in Solid Tumors version 1.1 and Common Terminology Criteria for Adverse Events version 5.0, respectively. Results: In total 65 patients were reviewed in this study, including 13 cases with ECOG performance status ≥2. Acral and mucosal cases accounted for 47.7% and 23.1% respectively. In 27(41.5%) patients, the combination therapy was used as the first line treatment, whereas in the rest 38 patients as second or subsequent lines. The median follow-up period was 8 months (1.5-21 months). Median OS was 15 months (95CI%: 10.62-19.38 months). Median PFS was 6 months (95CI%: 2.54-9.46 months). 6-month and 1-year PFS rate were 48.1% and 35.3%. 6-month and 1-year OS rate were 80.9% and 59.8%. Objective response was seen in 18.46% cases, with 12.31% of patients exhibiting ongoing response. The best confirmed disease control rate was 73.85%. Multivariate analysis demonstrated that overall survival was significantly associated with ECOG performance status ≥2 (OR=3.32，95%CI=1.14-9.66 ), regardless of age(≥65), elevated LDH, PD-1 inhibitor type and the line of the combination therapy. Select treatment related AEs (TRAEs) of any grade were observed in 57(87.69%) patients. The leading 3 TRAEs were lymphopenia, fatigue and fever. Grade 3 to 4 TRAEs were recorded in 2 cases. Grade 4 hyponeutrophilia occurred in a patient with ECOG status 3 using interferon-α1b plus toripalimab and resulted in discontinuation of both PD-1 inhibitor and IFN-α1b. Grade 3 headache was reported by one patient using interferon-α1b plus pembrolizumab and was solved with celecoxib 200mg daily. No drug-related deaths were reported. Conclusions: PD-1 inhibitor combining interferon-α1b therapy shows promising efficacy and acceptable toxicity in this real-world cohort of Chinese metastatic melanoma patients.[Table: see text]

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