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 Some aspects of nivolumab administration in treatment for metastatic melanoma (clinical cases)

2021 ◽  
pp. 64-74
Author(s):  
L. Yu. Vladimirova ◽  
A. Eh. Storozhakova ◽  
I. L. Popova ◽  
S. N. Kabanov ◽  
N. A. Abramova ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Brain Metastases ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Skin Toxicity ◽  
Complete Regression ◽  
Cutaneous Toxicity ◽  
First Case

The development of a new direction in anticancer medical therapy – the use of immune checkpoint inhibitors targeting PD-1/ PD-L1 and CTLA-4 – has significantly changed the approach to tumor treatment in the last few years. The PD1 blocker nivolumab in major registered clinical trials improved overall survival, including in metastatic melanoma, with a favorable toxicity profile. However, its efficacy in patients with brain metastases from melanoma was poorly studied, since the inclusion criteria  for  most clinical trials do not envisage recruiting such patients. The  immune-mediated toxicity of  immune checkpoint inhibitors is currently well enough studied. However, cases of cutaneous toxicity are quite rare and present certain difficulties for differential diagnosis and treatment. This article presents two cases of effective nivolumab treatment in patients with generalized BRAFwt and BRAFmut cutaneous melanoma. The  first case is of  interest due to the  presence of  brain  metastases in the patient. Nivolumab therapy helped achieving complete regression of intracranial metastases with the long-term effect. The second case, in addition to effective treatment, demonstrates a rare manifestation of skin toxicity – vitiligo on the face and upper extremities.

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 Clinical Development of Immune Checkpoint Inhibitors

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Ayumu Ito ◽  
Shunsuke Kondo ◽  
Kohei Tada ◽  
Shigehisa Kitano
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
Metastatic Melanoma ◽  
Tumor Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Clinical Development ◽  
Phase Iii ◽  
Immune Checkpoint Molecules

Recent progress in cancer immunotherapy has been remarkable. Most striking are the clinical development and approval of immunomodulators, also known as immune checkpoint inhibitors. These monoclonal antibodies (mAb) are directed to immune checkpoint molecules, which are expressed on immune cells and mediate signals to attenuate excessive immune reactions. Although mAbs targeting tumor associated antigens, such as anti-CD20 mAb and anti-Her2 mAb, directly recognize tumor cells and induce cell death, immune checkpoint inhibitors restore and augment the antitumor immune activities of cytotoxic T cells by blocking immune checkpoint molecules on T cells or their ligands on antigen presenting and tumor cells. Based on preclinical data, many clinical trials have demonstrated the acceptable safety profiles and efficacies of immune checkpoint inhibitors in a variety of cancers. The first in class approved immune checkpoint inhibitor is ipilimumab, an anti-CTLA-4 (cytotoxic T lymphocyte antigen-4) mAb. Two pivotal phase III randomized controlled trials demonstrated a survival benefit in patients with metastatic melanoma. In 2011, the US Food and Drug Administration (FDA) approved ipilimumab for metastatic melanoma. Several clinical trials have since investigated new agents, alone and in combination, for various cancers. In this review, we discuss the current development status of and future challenges in utilizing immune checkpoint inhibitors.

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.

Sustained clinico-radiologic response to anti-cytotoxic T lymphocyte antigen 4 antibody therapy in metastatic myxoid liposarcoma

2016 ◽  
Vol 23 (7) ◽  
pp. 549-551
Author(s):  
Constantin A Dasanu
Keyword(s):  
Metastatic Melanoma ◽  
T Lymphocyte ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Antibody Therapy ◽  
Myxoid Liposarcoma ◽  
Effective Control ◽  
Lymphocyte Antigen

Rarity and heterogeneity of sarcomas pose significant challenges in terms of developing new therapies. Therefore, efforts towards studying immunotherapy in sarcomas may provide hope for effective control of this group of devastating cancers. A sustained clinico-radiologic response to the anti-cytotoxic T lymphocyte antigen 4 antibody ipilimumab in a patient with metastatic myxoid liposarcoma is reported. Although the patient was treated with this agent for metastatic melanoma, both his metastatic cancers – melanoma and sarcoma – meaningfully responded to this agent. Consideration of enrolling patients in immunotherapy trials using various immune checkpoint inhibitors, where available, is of paramount importance, especially when facing advanced and/or refractory sarcoma situation.

scholarly journals The survivorship experience of patients with metastatic melanoma on long-term immune checkpoint inhibitors

2018 ◽  
Vol 29 ◽  
pp. ix105
Author(s):  
J.E. Lai-Kwon ◽  
C. Khoo ◽  
S. Lo ◽  
D. Milne ◽  
M. Mohamed ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

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.

scholarly journals A new biological triangle in cancer: intestinal microbiota, immune checkpoint inhibitors and antibiotics

2021 ◽  
Author(s):  
Jie Zhang ◽  
Zhujiang Dai ◽  
Cheng Yan ◽  
Wenjie Zhang ◽  
Daorong Wang ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Epidemiological Studies ◽  
Term Survival ◽  
Checkpoint Inhibitor Therapy ◽  
Rational Use Of Antibiotics

AbstractCancer immunotherapy has revolutionized the treatment of many malignant tumors. Although immune checkpoint inhibitors (ICIs) can reactivate the anti-tumor activity of immune cells, sensitivity to immune checkpoint inhibitor therapy depends on the complex tumor immune processes. In recent years, numerous researches have demonstrated the role of intestinal microbiota in immunity and metabolism of the tumor microenvironment, as well as the efficacy of immunotherapy. Epidemiological studies have further demonstrated the efficacy of antibiotic therapy on the probability of patients' response to ICIs and predictability of the short-term survival of cancer patients. Disturbance to the intestinal microbiota significantly affects ICIs-mediated immune reconstitution and is considered a possible mechanism underlying the development of adverse effects during antibiotic-based ICIs treatment. Intestinal microbiota, antibiotics, and ICIs have gradually become important considerations for the titer of immunotherapy. In the case of immunotherapy, the rational use of antibiotics and intestinal microbiota is expected to yield a better prognosis for patients with malignant tumors.

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