scholarly journals Potential utilization of neopterin measurements in the assessment of pyrexia in metastatic melanoma treated with combined targeted therapy: a case report

Pteridines ◽  
2020 ◽  
Vol 31 (1) ◽  
pp. 151-157 ◽  
Author(s):  
Marie Bartoušková ◽  
Michaela Hrouzková ◽  
Filip Čtvrtlík ◽  
Pavla Petrová ◽  
Nikol Rušarová ◽  
...  
Keyword(s):  
Case Report ◽  
Targeted Therapy ◽  
Metastatic Melanoma ◽  
Immune Activation ◽  
Checkpoint Inhibitors ◽  
Metastatic Malignant Melanoma ◽  
Marked Rise ◽  
Present Case Report ◽  
Improved Outcomes ◽  
Urinary Neopterin

AbstractIn patients with metastatic melanoma the advent of targeted therapy and immune checkpoint inhibitors has transformed the management of advanced and metastatic disease, resulting in improved outcomes. Neopterin is a biomarker of immune activation increased in cancer as well as in other conditions associated with immune activation. We present a case of a patient with advanced metastatic melanoma responding to the combination targeted therapy with dabrafenib and trametinib. The treatment was complicated by a fever that was accompanied by a marked rise in serum and urinary neopterin concentrations. Present case report illustrates not only the efficacy of combined targeted therapy, but also the utilization of neopterin measurements in the diagnosis and monitoring of pyrexia in patients with metastatic malignant melanoma.

scholarly journals Response to Ipilimumab/Nivolumab Rechallenge and BRAF Inhibitor/MEK Inhibitor Rechallenge in a Patient with Advanced Metastatic Melanoma Previously Treated with BRAF Targeted Therapy and Immunotherapy

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Caitlyn N. Myrdal ◽  
Srinath Sundararajan
Keyword(s):  
Targeted Therapy ◽  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Objective Response ◽  
Braf Inhibitor ◽  
Mek Inhibitor ◽  
Optimal Sequencing ◽  
The Right

Little is known about the optimal sequencing of targeted therapy and immunotherapy in the treatment of patients with BRAFV600-mutated metastatic melanoma. BRAF/MEK inhibition often has the benefit of rapid disease regression; however, resistance is frequently seen with long-term use. Treatment with immune checkpoint inhibitors offers the potential for long-term response but displays a lower rate of objective response. The benefit of synergy between therapies is apparent; however, there is limited data regarding optimal sequencing in the treatment of advanced melanoma. We present the case of a 62-year-old gentleman with advanced BRAFV600-mutated melanoma who followed an unconventional treatment path. After progressing on single-agent vemurafenib, he had response to multiple modalities of immunotherapy before progression. After, he had a substantial response to multiple BRAF/MEK inhibitor rechallenges before developing resistance. The patient is now stable after a retrial of combination immunotherapy. Our case illustrates that with the right sequencing of therapy, meaningful clinical responses can be elicited with rechallenging of targeted therapy and immunotherapy in metastatic melanoma.

scholarly journals Patterns of treatment and BRAF testing with immune checkpoint inhibitors and targeted therapy in patients with metastatic melanoma presumed to be BRAF positive

2019 ◽  
Vol 29 (3) ◽  
pp. 301-310 ◽  
Author(s):  
Sameer Ghate ◽  
Raluca Ionescu-Ittu ◽  
Rebecca Burne ◽  
Briana Ndife ◽  
François Laliberté ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

scholarly journals Effective Immunotherapy in Bone Marrow Metastatic Melanoma Presenting with Disseminated Intravascular Coagulopathy

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Bolanle Gbadamosi ◽  
Daniel Ezekwudo ◽  
Bhadresh Nayak ◽  
Zhou Yu ◽  
Sandra Gjorgova-Gjeorgjievski ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Malignant Melanoma ◽  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Metastatic Malignant Melanoma ◽  
Critically Ill Patient ◽  
Low Grade ◽  
Disseminated Intravascular Coagulopathy ◽  
Intravascular Coagulopathy

Malignant melanoma is responsible for the majority of skin cancer deaths and is increasing in prevalence. Bone marrow (BM) involvement by melanoma is rare in the absence of widespread visceral disease. Here, we report the case of a 30-year-old female who presented to the hospital with back pain, low-grade fever, and easy bruising. She was found to be bicytopenic and in disseminated intravascular coagulopathy (DIC). Surprisingly, BM biopsy showed extensive involvement by metastatic malignant melanoma in the absence of visceral or brain metastasis. The unique presentation of this case and the challenge of management of a potentially treatable cancer in a critically ill patient are discussed, alongside a review of published cases of metastatic melanoma in the BM and an exploration of currently available treatment options. The excellent response of our patient to combined immune checkpoint inhibitors has yet to be paralleled in the available literature.

scholarly journals Metastatic Melanoma With Leptomeningeal Disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Amanda M. Marinova, MS, PA-C ◽  
Jennifer L. Reilly, CRNP, BSN, MSN, RN, AANP ◽  
Victoria Wong, MS, PA-C ◽  
Stephanie Weiss, MD ◽  
Anthony J. Olszanski, MD
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Case Report ◽  
Metastatic Melanoma ◽  
Central Nervous System Involvement ◽  
Leptomeningeal Disease ◽  
Leptomeningeal Involvement ◽  
Improved Outcomes ◽  
The Central Nervous System ◽  
Systemic Therapies

Leptomeningeal disease in patients with melanoma historically portends a grim prognosis, with median survival measured in weeks to months. The advent of effective immunotherapy and targeted agents may modify the outcome of such patients. This case report describes a 43-year-old patient diagnosed with stage IIIa BRAF-positive cutaneous melanoma in 2012 who subsequently developed leptomeningeal involvement as her sole site of melanotic metastasis. She received multiple systemic therapies and radiotherapy and survived 2.5 years after her diagnosis with central nervous system involvement. This case report highlights the importance of a multidisciplinary team and the advent of effective agents, which offers the potential for significantly improved outcomes for patients with metastatic melanoma involving the central nervous system.

SECOMBIT (sequential combo immuno and target therapy study): A three arms prospective, randomized phase II study to evaluate the best sequential approach with combo immunotherapy [ipilimumab (I) /nivolumab (N)] and combo target therapy [encorafenib (E)/binimetinib (B)] in patients with metastatic melanoma and BRAF mutation.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS9598-TPS9598
Author(s):  
Paolo Antonio Ascierto ◽  
Reinhard Dummer ◽  
Ignacio Melero ◽  
Giuseppe Palmieri ◽  
Diana Giannarelli ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Target Therapy ◽  
Response Rates ◽  
Immune Checkpoint Blockade ◽  
High Rate ◽  
Sequential Approach ◽  
The Right

TPS9598 Background: Treatment of BRAF-mutated metastatic melanoma has dramatically changed with the introduction of targeted therapy (BRAF and MEK inhibitors) and immune-checkpoint blockade (anti-CTLA4, anti-PD-1, and anti-PD-L1). Target therapy has been associated with high response rates, but short-term responses. Conversely, treatment with immune checkpoint inhibitors was found to present with lower response rates, but long-term responses. Synergism has been demonstrated when targeted therapy is combined with immunotherapy. The risk of a high rate of toxicity limits the simultaneous combination of all the four compounds (target agents and immunomodulating monoclonal antibodies). Sequencing of these different combinations seems to be more feasible; finding the right treatment sequence represents an important issue to be addressed. Methods: Approximately, 230 patients with untreated, histologically-confirmed advanced melanoma (measurable disease by RECIST v1.1) and carrying the BRAFV600 mutation will be randomized to Arm A [E+B until disease progression (PD), followed by I+N], or Arm B (I+N until PD, followed by E+B) or Arm C (E+B for 8 weeks, followed by I+N until PD, followed by E+B until PD). Patients will receive the combo treatments with the following schedules: target therapy, E 450mg p.o. od + B 45mg p.o. bid; immunotherapy, I 3mg/kg + N 1mg/kg Q3w x 4 cycles, followed by N 3mg/kg Q2w. The OS (time from the date of randomization until death from any cause) is primary efficacy endpoint of the study. Secondary endpoints include total PFS (time from randomization until the second progression), survival at 2 and 3 years, best overall response rate, duration of response. About 90 patients will take part in the ancillary study for the evaluation of biomarkers on the biological samples available (biopsies + blood samples). 30 Sites in Europe will concur to enroll the patients in the trial. This study is open and currently enrolling patients. Clinical trial information: NCT02631447.

scholarly journals Uncommon BRAF Mutations Associated with Durable Response to Immunotherapy in Patients with Metastatic Melanoma

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Brenen P. Swofford ◽  
Jade Homsi
Keyword(s):  
Targeted Therapy ◽  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Disease Process ◽  
Complete Response ◽  
Therapeutic Benefit ◽  
Braf Mutations ◽  
Durable Response ◽  
Melanoma Patients ◽  
Potential Therapeutic Benefit

Melanoma is a disease process which has been increasing in incidence over the past three decades and metastatic melanoma carries a poor prognosis. Through genetic studies of this disease, it has been determined that the BRAF V600 mutation plays a major role in the pathophysiology of the disease and this has led to the utilization of targeted therapy (BRAF and MEK inhibitors) in its treatment. Other BRAF mutations (non-V600 mutations) are rare in melanoma and targeted therapy is not indicated for patients with these mutations due to reduced response rates. An emerging option for metastatic melanoma with uncommon BRAF mutations is immunotherapy using checkpoint inhibitors such as PD-1 inhibitors or CTLA-4 inhibitors. Currently, it is unknown how patients with BRAF non-V600 mutations respond to immunotherapy. This report will examine the effect of immunotherapy on two distinct metastatic melanoma patients, each with uncommon BRAF mutations, occurring outside the V600 locus (E586K and G469E). These patients were noted to have a durable, complete response when treated with immunotherapy and continue to exhibit a response 9 and 15 months after discontinuing therapy. Further research and clinical trials are needed to study patients with uncommon BRAF mutations and the potential therapeutic benefit of immunotherapy.

scholarly journals Immune Checkpoint Inhibitor Induced Pericarditis and Encephalitis in a Patient Treated With Ipilimumab and Nivolumab for Metastatic Melanoma: A Case Report and Review of the Literature

2021 ◽  
Vol 11 ◽  
Author(s):  
Jorja Braden ◽  
Jenny H. Lee
Keyword(s):  
Pericardial Effusion ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Drug Exposure ◽  
Checkpoint Inhibitors ◽  
Autoimmune Encephalitis ◽  
Complete Response ◽  
High Dose ◽  
Pericardial Disease ◽  
Improved Outcomes

Immune checkpoint inhibitors (ICIs) have dramatically improved outcomes in melanoma. Common ICI toxicities have become familiar to clinicians; however, rare delayed toxicities remain challenging given the paucity of data with such presentations. We present the unique case of a 61-year-old with metastatic melanoma with two rare, delayed ICI-induced toxicities. After resection of a large symptomatic parietal metastases, this patient received two doses of combination ipilimumab and nivolumab. Five weeks following his second dose, he developed ICI-induced pericarditis with associated pericardial effusion and early signs of tamponade. Corticosteroids were not administered due to a concurrent cerebral abscess. Administration of colchicine, ibuprofen, judicious monitoring, and cessation of immunotherapy led to the complete resolution of the effusion over several weeks. Seven months following his last dose of immunotherapy, the patient developed ICI-associated grade four autoimmune encephalitis, presenting as status epilepticus. High-dose steroid initiation led to rapid clinical improvement. The patient remains in near-complete response on imaging with no recurrence of pericardial effusion and partial resolution of neurological symptoms. ICI-induced pericardial disease and encephalitis carry substantial mortality rates and prompt diagnosis and management is critical. Clinicians must therefore remain vigilant for these rare toxicities regardless of duration of drug exposure or time since cessation of therapy.

scholarly journals Acute renal transplant rejection following nivolumab therapy for metastatic melanoma

2021 ◽  
Vol 14 (2) ◽  
pp. e238037
Author(s):  
Brandon Tan ◽  
Mark Baxter ◽  
Richard Casasola
Keyword(s):  
Renal Transplant ◽  
Metastatic Melanoma ◽  
Immune Evasion ◽  
Checkpoint Inhibitors ◽  
Transplant Rejection ◽  
Immune Recognition ◽  
Transplant Recipients ◽  
Oncological Outcomes ◽  
Improved Outcomes ◽  
Renal Transplant Rejection

Cancers can develop the ability to evade immune recognition and destruction. Immune checkpoint inhibitors (ICIs) are drugs targeting these immune evasion mechanisms. ICIs have significantly improved outcomes in several cancers including metastatic melanoma. However, data on toxicities associated with allograft transplant recipients receiving ICI is limited. We describe a case of a 71-year-old woman who was diagnosed with metastatic melanoma 13 years after renal transplantation. She was commenced on the ICI nivolumab. She developed acute renal transplant rejection 15 days after administration of the first dose. She continues on haemodialysis but has demonstrated complete oncological response. This case demonstrates the risk of acute renal transplant rejection versus improved oncological outcomes. Patients and clinicians must consider this balance when initiating ICI therapy in allograft transplant recipients. Patients should be fully consented of the potential consequences of acute renal transplant rejection including lifelong dialysis.

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