Cures with B-Raf inhibitors as single agents in metastatic B-Raf mutated melanoma: Curb your enthusiasm?

2020 ◽  
pp. 107815522097507
Author(s):  
Constantin A Dasanu
Keyword(s):  
Radiation Therapy ◽  
Malignant Melanoma ◽  
Clinical Outcome ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibitor Therapy ◽  
Favorable Clinical Outcome

Development of brain metastases during treatment with B-raf/MEK inhibitors for malignant melanoma tends to be more frequent than during immune checkpoint inhibitor therapy. Long-term responders to B-Raf inhibitors with or without MEK inhibition should be monitored very closely clinico-radiologically for a potential relapse. In addition to surgery and/or radiation therapy, single or dual immune checkpoint inhibitor therapy should be started without delay in this setting to ensure a favorable clinical outcome.

scholarly journals Case Report: A case of immune checkpoint inhibitor therapy in a patient with multiple sclerosis

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1167
Author(s):  
Raju Vaddepally ◽  
Soujanya Sodavarapu ◽  
Anupama Kutadi ◽  
Wesley Taylor ◽  
Navneeth Kumar
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Malignant Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Response To Treatment ◽  
High Dose ◽  
Checkpoint Inhibitor Therapy

Immune checkpoint inhibitors (ICIs) have rapidly shifted the landscape of treatments in malignancy with significant improvements in survival paradigm. They have been an attractive armamentarium to the oncologists given the limited immune adverse effects with potential for deeper and durable benefits that haven't been previously noticed with chemotherapy. However, they result in unique toxicities by limiting immune self-tolerance and cause immune-mediated endocrinopathies, such as hypothyroidism, pneumonitis, colitis, hepatitis, myocarditis, meningitis, hypophysitis, etc. As such, they are contraindicated in patients with autoimmune disorders or recipients of organ transplants given the risk for reactivation or flare of the underlying autoimmune disease and rejection of the donor organ in transplants, although sporadic cases have been reported with the use of immunotherapy in such patients. Malignant melanoma is a highly aggressive cancer, with only 15-20% five-year survival rate once it has spread to the lymph nodes or has distant metastasis. ICIs have changed the landscape of advanced melanoma with exponential improvements in survival, the 5-year survival rates are about 50%. Multiple sclerosis (MS) is recognized as T cell-mediated immune response causing inflammation, which causes local inflammatory plaques and demyelination. ICIs are likely to generate an immune response that causes molecular mimicry and cross-react with CNS autoantigens, in turn exacerbating pre-existing immune response and subsequent flare-ups in MS. There is little knowledge about treating such patients with immunotherapy, short of a few case reports and series; in this report, we describe another such case. We present a case of checkpoint inhibitor therapy in a patient with multiple sclerosis who underwent immune checkpoint inhibitor therapy with pembrolizumab for metastatic malignant melanoma who had a complete response to treatment at the cost of MS relapse, which was managed with high-dose steroids.

scholarly journals SAT-473 Thyroid Dysfunction in a Patient with Malignant Melanoma Treated with Immune Checkpoint Blockade

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Shaveta Gupta ◽  
Ngwe Yin
Keyword(s):  
Malignant Melanoma ◽  
Immune Checkpoint ◽  
Thyroid Dysfunction ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Immune Checkpoint Blockade ◽  
Inhibitor Therapy ◽  
Checkpoint Blockade ◽  
Thyroid Disorders ◽  
Checkpoint Inhibitor Therapy

Abstract Thyroid Dysfunction in a Patient with Malignant Melanoma Treated with Immune Checkpoint Blockade Background: Thyroid dysfunction is a known immune-related adverse event associated with immune checkpoint inhibitor therapy. Clinical Case: 48 year old female, newly diagnosed with metastatic melanoma started on combination immune checkpoint inhibitor therapy with Ipilimumab and Nivolumab. Her baseline thyroid function tests were normal. 6 weeks after the first cycle, she was found to have TSH of 0.010IU/ml with FT4 3.33IU/ml. Patient was started on Prednisone for 2 weeks and beta-blocker for symptom control by oncology team and referred to endocrine clinic for further evaluation. She was diagnosed with thyroiditis. TSI and thyroid uptake scan were not checked as there was no clinical suspicion for Graves disease in the absence of ophthalmopathy and thyroid enlargement. Serial TFTs were obtained which showed improvement. However, 4 weeks later, patient developed overt hypothyroidism (TSH 11.800IU/ml, FT4 0.68IU/ml) for which therapy with levothyroxine was started. Conclusion: Our case emphasizes the importance of close monitoring of patients receiving Immune Checkpoint Inhibitor Therapy for prompt diagnosis and management of the thyroid disorders to prevent complications such as thyroid storm or myxedema coma. Per the ASCO guidelines, Brahmer et al recommends monitoring TFTs every 4 to 6 weeks from the start of the therapy and every 2-3 weeks after the diagnosis to detect conversion of thyroiditis and hyperthyroidism to hypothyroidism. In the combination therapy, the median time to onset of hyperthyroidism and hypothyroidism after first treatment was 21 and 63 days and transition time from hyperthyroidism to hypothyroidism was 42 days. Reference: (1) Characterization of Thyroid Disorders in Patients Receiving Immune Checkpoint Inhibition Therapy Lee et al (2) Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline Julie R. Brahmer et al

A case of malignant melanoma with repeated development of drug eruption during immune checkpoint inhibitor therapy

Skin Cancer ◽  
2019 ◽  
Vol 34 (2) ◽  
pp. 198-202
Author(s):  
Nagisa FUJIMORI ◽  
Yuka KOBAYASHI ◽  
Sayaka TOGO ◽  
Akari KAGANOI ◽  
Kentaro OZAWA ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Immune Checkpoint ◽  
Drug Eruption ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibitor Therapy

scholarly journals Correlative Monitoring of Immune Activation and Tissue Damage in Malignant Melanoma—An Algorithm for Identification of Tolerance Breakage During Immune Checkpoint Inhibitor Therapy of Cancer

2020 ◽  
Vol 21 (6) ◽  
pp. 2020 ◽  
Author(s):  
Renate U. Wahl ◽  
Marike Leijs ◽  
Arturo Araujo ◽  
Albert Rübben
Keyword(s):  
Malignant Melanoma ◽  
Adverse Events ◽  
Immune Activation ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Immune Reaction ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibition ◽  
Checkpoint Inhibitor Therapy

We describe an innovative approach for identification of tolerance breakage during immune checkpoint inhibitor therapy in malignant melanoma. Checkpoint inhibitor therapy enhances the immunologic clearance of cancer by suppressing pathways which induce immune suppression and tolerance. We posit that by analyzing temporal correlations of key markers of immune activation and tissue damage it would be possible to detect the onset of anticancer immune reaction as well as of immunologic adverse effects which might become crucial for optimization as well as safety of immune checkpoint inhibitor treatment. We analyzed time courses of routine laboratory values of serum tumor markers as well as of markers of immune activation in 17 patients with metastasized malignant melanoma receiving checkpoint inhibition and weekly laboratory controls. A parallel serum level increase of interleukin-6 and the tumor marker S100B could be identified in 13 patients, suggesting that the onset of tolerance breakage under checkpoint inhibition may be identified and measured. Immune-related adverse events in the patients were also accompanied by a peak of IL-6. In six patients, the onset of a putative anticancer immune reaction and the beginning of immunologic adverse events occurred in the same treatment cycle; in six patients the immunologic adverse reactions took place in separate cycles.

A Systematic Review of Cases of Diabetes Mellitus following Immune Checkpoint Inhibitor Therapy for Cancer

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 204-LB ◽  
Author(s):  
KARA R. MIZOKAMI-STOUT ◽  
ROMA GIANCHANDANI ◽  
MARK MACEACHERN ◽  
RAVI M. IYENGAR ◽  
SARAH YENTZ ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibitor Therapy

scholarly journals Collaboration Between Rheumatology and Oncology in Immune Checkpoint Inhibitor Therapy

2018 ◽  
Vol 36 (26) ◽  
pp. 2743-2744 ◽  
Author(s):  
Donald L. Kimpel ◽  
Janet E. Lewis ◽  
Elizabeth Gaughan ◽  
William W. Grosh ◽  
Christiana Brenin
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibitor Therapy
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