scholarly journals Switching to Immune Checkpoint Inhibitors upon Response to Targeted Therapy; The Road to Long-Term Survival in Advanced Melanoma Patients with Highly Elevated Serum LDH?

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1940 ◽  
Author(s):  
Maartje G. Schouwenburg ◽  
Karijn P.M. Suijkerbuijk ◽  
Rutger H.T. Koornstra ◽  
Anouk Jochems ◽  
Michiel C.T. van Zeijl ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Elevated Serum ◽  
Subsequent Treatment ◽  
Advanced Melanoma ◽  
Term Survival ◽  
Melanoma Patients

The prognosis of patients with advanced melanoma has improved dramatically. However, the clinical outcomes of patients with highly elevated serum lactate dehydrogenase (LDH) remain very poor. The aim of this study was to explore whether patients with normalized LDH after targeted therapy could benefit from subsequent treatment with immune checkpoint inhibitors (ICI). Data from all patients with BRAF-mutant metastatic melanoma with a highly elevated serum LDH at baseline (≥2× upper limit of normal) receiving first-line targeted therapy between 2012 and 2019 in the Netherlands were collected. Patients were stratified according to response status to targeted therapy and change in LDH at start of subsequent treatment with ICI. Differences in overall survival (OS) between the subgroups were compared using log-rank tests. After a median follow-up of 35.1 months, median OS of the total study population (n = 360) was 4.9 months (95% CI 4.4–5.4). Of all patients receiving subsequent treatment with ICI (n = 113), survival from start of subsequent treatment was significantly longer in patients who had normalized LDH and were still responding to targeted therapy compared to those with LDH that remained elevated (median OS 24.7 vs. 1.1 months). Our study suggests that introducing ICI upon response to targeted therapy with normalization of LDH could be an effective strategy in obtaining long-term survival in advanced melanoma patients with initial highly elevated serum LDH.

scholarly journals Long-Term Survival, Quality of Life, and Psychosocial Outcomes in Advanced Melanoma Patients Treated with Immune Checkpoint Inhibitors

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Anne Rogiers ◽  
Annelies Boekhout ◽  
Julia K. Schwarze ◽  
Gil Awada ◽  
Christian U. Blank ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Advanced Melanoma ◽  
Term Survival ◽  
Psychosocial Wellbeing

Immune checkpoint inhibitors have become a standard of care option for the treatment of patients with advanced melanoma. Since the approval of the first immune checkpoint (CTLA-4) inhibitor ipilimumab in 2011 and programmed death-1 (PD-1) blocking monoclonal antibodies pembrolizumab and nivolumab thereafter, an increasing proportion of patients with unresectable advanced melanoma achieved long-term overall survival. Little is known about the psychosocial wellbeing, neurocognitive function, and quality of life (QOL) of these survivors. Knowledge about the long term side-effects of these novel treatments is scarce as long-term survivorship is a novel issue in the field of immunotherapy. The purpose of this review is to summarize our current knowledge regarding the survival and safety results of pivotal clinical trials in the field of advanced melanoma and to highlight potential long-term consequences that are likely to impact psychosocial wellbeing, neurocognitive functioning, and QOL. The issues raised substantiate the need for clinical investigation of these issues with the aim of optimizing comprehensive health care for advanced melanoma survivors.

Immunotherapy for advanced melanoma: current situation in Japan

2020 ◽  
Vol 51 (1) ◽  
pp. 3-9
Author(s):  
Junji Kato ◽  
Hisashi Uhara
Keyword(s):  
Uveal Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Advanced Melanoma ◽  
Current Evidence ◽  
Clinical Effects ◽  
Durable Response ◽  
Term Survival

Abstract Treatment with immune checkpoint inhibitors provides long-term survival for patients with advanced melanoma. Improvements in the overall survival of advanced melanoma patients have been achieved with anti-PD-1 monotherapy and anti-PD-1+ CTLA4 combination therapy, but there are still many issues to resolve. Acral, mucosal and uveal melanoma have been less responsive to immune checkpoint inhibitors than cutaneous melanoma. For patients who have achieved a good response, it is still not known how long the anti-PD-1 therapy should be administered. Moreover, there is limited treatment for patients who relapse during or after adjuvant anti-PD-1 therapy. Here, we review the current evidence regarding the clinical effects of immunotherapy for advanced melanoma. Moreover, we review previous studies of acral, mucosal and uveal melanoma, and we discuss the recent findings regarding durable response after the cessation of anti-PD-1 therapy, and treatment options for recurrence after adjuvant therapy.

scholarly journals Antibiotics are associated with decreased progression-free survival of advanced melanoma patients treated with immune checkpoint inhibitors

2019 ◽  
Vol 8 (4) ◽  
pp. e1568812 ◽  
Author(s):  
Arielle Elkrief ◽  
Layal El Raichani ◽  
Corentin Richard ◽  
Meriem Messaoudene ◽  
Wiam Belkaid ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Free Survival ◽  
Melanoma Patients

Association between immune-related adverse events and long-term survival outcomes in patients treated with immune checkpoint inhibitors

2020 ◽  
Vol 132 ◽  
pp. 61-70 ◽  
Author(s):  
Denis Maillet ◽  
Pauline Corbaux ◽  
Jean-Jacques Stelmes ◽  
Stéphane Dalle ◽  
Myriam Locatelli-Sanchez ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Survival Outcomes ◽  
Term Survival ◽  
Long Term Survival

scholarly journals Anti-PD-1 and Novel Combinations in the Treatment of Melanoma—An Update

2020 ◽  
Vol 9 (1) ◽  
pp. 223 ◽  
Author(s):  
Frank Gellrich ◽  
Marc Schmitz ◽  
Stefan Beissert ◽  
Friedegund Meier
Keyword(s):  
Clinical Trials ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Tumor Burden ◽  
Term Survival ◽  
Combination Regimens

Until recently, distant metastatic melanoma was considered refractory to systemic therapy. A better understanding of the interactions between tumors and the immune system and the mechanisms of regulation of T-cells led to the development of immune checkpoint inhibitors. This review summarizes the current novel data on the treatment of metastatic melanoma with anti-programmed cell death protein 1 (PD-1) antibodies and anti-PD-1-based combination regimens, including clinical trials presented at major conference meetings. Immune checkpoint inhibitors, in particular anti-PD-1 antibodies such as pembrolizumab and nivolumab and the combination of nivolumab with the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody ipilimumab can achieve long-term survival for patients with metastatic melanoma. The anti-PD-1 antibodies nivolumab and pembrolizumab were also approved for adjuvant treatment of patients with resected metastatic melanoma. Anti-PD-1 antibodies appear to be well tolerated, and toxicity is manageable. Nivolumab combined with ipilimumab achieves a 5 year survival rate of more than 50% but at a cost of high toxicity. Ongoing clinical trials investigate novel immunotherapy combinations and strategies (e.g., Talimogene laherparepvec (T-VEC), Bempegaldesleukin (BEMPEG), incorporation or sequencing of targeted therapy, incorporation or sequencing of radiotherapy), and focus on poor prognosis groups (e.g., high tumor burden/LDH levels, anti-PD-1 refractory melanoma, and brain metastases).

scholarly journals Hyperprogressive disease rarely occurs during checkpoint inhibitor treatment for advanced melanoma

2020 ◽  
Author(s):  
M. Schuiveling ◽  
E. H. J. Tonk ◽  
R. J. Verheijden ◽  
K. P. M. Suijkerbuijk
Keyword(s):  
Tumor Growth ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Evaluation Criteria ◽  
Tumor Burden ◽  
Advanced Melanoma ◽  
Tumor Growth Rate ◽  
Biological Entity ◽  
Melanoma Patients

Abstract Introduction Hyperprogression, characterized by a rapid acceleration in tumor growth, is a novel pattern of progression recently described in patients treated with immune checkpoint inhibitors. This study aims to assess the incidence of hyperprogression in patients with advanced melanoma treated with checkpoint inhibitors. Methods Clinical and radiological findings of all advanced melanoma patients who started checkpoint inhibitors between January 2013 and March 2019 in a tertiary academic center in the Netherlands were analyzed. Change in tumor burden was calculated by assessing volumetric tumor growth using the criteria as defined by immune Response Evaluation Criteria in Solid Tumors version 1.1. Hyperprogression was defined as a time to treatment failure less than 2 months with doubling of tumor burden and a twofold increase in tumor growth rate during treatment. Possible hyperprogression was defined as the presence of the first two criteria in the absence of a pre-baseline scan. Results Out of 206 treatment episodes in 168 patients, 75 were evaluable for hyperprogression and 87 for possible hyperprogression. Hyperprogression was observed in one patient (1.3%) and possible hyperprogression was observed in one patient (1.1%). Conclusion Hyperprogression is rare in melanoma patients treated with immune checkpoint inhibitors. Our data question if hyperprogression really is a biological entity in metastatic melanoma.

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