Immune checkpoint inhibitor-induced subacute cutaneous lupus erythematosus: a case report and review of the literature.

Immune checkpoint inhibitor (ICI) use has been associated with numerous autoimmune side effects, known as immune related adverse events (irAEs). Cutaneous irAEs are common and affect up to 50% of patients treated with ICIs. There have been an increasing number of cases reported in the literature regarding ICI-induced subacute cutaneous lupus erythematosus (SCLE). ICI-induced SCLE is important to recognize as it can result in a delayed and/or prolonged skin reaction despite treatment discontinuation. We describe a patient with gastro-esophageal adenocarcinoma who developed SCLE following one cycle of nivolumab treatment. A 75-year-old man presented to our clinic with a new photo-distributed rash composed of oval scaly pink papules and plaques involving his chest and arms. Despite treatment with topical corticosteroids, he presented to the emergency department 1 week later with worsening rash. Skin biopsy showed vacuolar interface pattern, along with superficial perivascular lymphocytic infiltrate, consistent with a drug eruption. The clinicopathological presentation was consistent with ICI-induced SCLE. Nivolumab treatment was discontinued due to the severity of the rash. The rash remitted with systemic corticosteroids, high potency topical steroids, and hydroxychloroquine. Unfortunately, the patient developed intraperitoneal metastatic disease, and was enrolled in hospice care. In this paper, we highlight the importance of early identification and treatment of this irAE. A review of the literature, including a discussion on the management of ICI-induced SCLE is also provided.

Melatonin Supplementation for Cancer-Related Fatigue in Patients With Early Stage Breast Cancer Receiving Radiotherapy: A Double-Blind Placebo-Controlled Trial.

BACKGROUND: Fatigue is common in patients undergoing radiotherapy (RT) and can significantly impact quality of life. Melatonin, a safe inexpensive natural supplement, may improve symptoms and attenuate the side effects of RT. The purpose of this randomized double-blind placebo-controlled phase III trial was to assess the effects of melatonin for preventing fatigue and other symptoms in patients with breast cancer undergoing RT. METHODS: Female early stage or Ductal carcinoma in situ patients with breast cancer ≥18 years of age with Eastern Cooperative Oncology Group (ECOG) performance status <3, hemoglobin ≥9 g/dL, planned for outpatient RT treatment with curative intent, were randomized 1:1 to melatonin 20 mg or placebo, orally, starting the night before RT initiation until 2 weeks post-RT. Randomization was stratified according to treatment duration (<3 weeks, ≥3 weeks) and prior chemotherapy. The primary endpoint was the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue scale), and secondary endpoints were FACIT-F subscales, Edmonton Symptom Assessment Scale (ESAS), and Patient-Reported Outcomes Measurement Information System (PROMIS) scores obtained at baseline, and 2 and 8 weeks post-RT. A 2-sided ANOVA F-test at a 4.5% significance level for the primary endpoint was used. Secondary analyses were reported using an F-test at a 5% significance level. The goal was to recruit approximately 140 patients with interim analysis planned mid-recruitment. RESULTS: Eighty-five patients were screened for eligibility; 79 patients were randomized: 40 to melatonin and 39 to placebo; 78 patients were treated and included in the interim analysis at the mid-recruitment point. Baseline patient characteristics of age, race, and ECOG performance status were similar in both arms. The treatment effect was studied using a longitudinal mixed effects model with the effect of treatment over time (treatment × time) as the primary outcome parameter. The treatment × time for FACIT-Fatigue did not demonstrate statistical significance (P-value .83) in the melatonin group compared to placebo. In addition, secondary analyses of FACIT physical, social, emotional, and functional well-being scores did not demonstrate statistical significance (P-values of .35, .06, .62, and .71, respectively). Total PROMIS scores, collected as secondary outcome reported by patients, did not demonstrate statistically significant change over time either (P-value is .34). The other secondary scale, ESAS, was analyzed for each individual item and found to be nonsignificant, anxiety (P = .56), well-being (.82), drowsiness (.83), lack of appetite (.35), nausea (.79), pain (.50), shortness of breath (.77), sleep (.45), and tiredness (.56). Depression was the only item demonstrating statistical significance with a decrease of 0.01 unit in the placebo group, a change not considered clinically significant. Melatonin was well-tolerated with no grade 3 or 4 adverse events reported. The most common side effects were headache, somnolence, and abdominal pain. No patients died while participating in this study. Two patients died within a year of study completion from breast cancer recurrence. Sixteen patients withdrew prior to study completion for various reasons including adverse events, hospitalizations unrelated to study drug, RT discontinuation, and COVID-19 precautions. CONCLUSIONS: In this double-blind placebo-controlled phase III trial, melatonin did not prevent or significantly improve fatigue and other symptoms in patients with early stage breast cancer undergoing RT. The analysis, showing little evidence of an effect, at mid-recruitment, assured early termination of the trial.

Salvage lenvatinib/everolimus combination therapy after immune checkpoint inhibitor and VEGFR tyrosine kinase inhibitor for metastatic renal cell carcinoma.

Background: The optimal treatment for metastatic renal cell carcinoma (mRCC) patients who have progressed after both immune checkpoint inhibitor (ICI) and VEGFR tyrosine kinase inhibitor (TKI) remains uncertain. Lenvatinib and everolimus (LE) are frequently used in combination as salvage therapy because of their different antitumor mechanisms, but efficacy and toxicity data in this setting are lacking. Methods: We retrospectively reviewed charts from two academic centers for 71 adult mRCC patients who received LE after prior ICI and TKI exposure. We evaluated patient demographics, histology, International mRCC Database Consortium (IMDC) risk group, treatment history, and toxicity details. Outcomes of interest included objective response rate (ORR), time to treatment failure (TTF), overall survival (OS), ≥grade 3 toxicities, and schedule or dosage changes, which were evaluated using descriptive statistics, chi-square test, Cox proportional hazards model, and the Kaplan-Meier method. Results: The median age was 64 (range 31-84). Most patients had clear cell histology (84.5%) and had undergone nephrectomy (80.3%). IMDC risks were favorable (19.7%), intermediate (int) (66.2%), poor (11.3%), and unknown (2.8%). The average ORR was 26.8%, while the median TTF was 5.5 months (95% confidence interval [CI], 3.5-7.6) and the median OS was 9 months (95% CI, 7.6-12.9). Intermediate and poor IMDC risks were independently associated with a significantly worse TTF compared to favorable risk (hazard ratio (HR), 3.03, 95% CI, 1.18-7.79), as was ≥4L treatment vs. 2L/3L treatment (HR, 2.02, 95% CI, 1.08-3.8). Of the 71 patients, 57.7% had ≥grade 3 adverse events, 60% had treatment interruption, 44.3% had dose reduction, and 21% stopped treatment due to intolerance. Conclusions: LE therapy is feasible but has modest efficacies following ICI/TKI treatment. Patients with favorable risk or treated earlier may have a better treatment response. These observations need to be confirmed in prospective studies.

Recent Advances in Immunotherapy for Patients with Head and Neck Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (CSCC) is the second most common non-melanoma skin cancer. A majority of patients present with localized disease, but some can present with locally advanced or metastatic disease. Most of these advanced cases occur in the anatomical head and neck region and are associated with more aggressive disease, necessitating prompt and effective treatment. Prior to the emergence of immunotherapy, systemic treatment options were limited to platinum-based chemotherapy and salvaged with targeted epidermal growth factor therapy. These therapies were associated with poor efficacy and increased toxicity in an often frail, older population. Immunotherapy has dramatically improved outcomes in this patient population due to its favorable side effect profile, durable treatment response, and improved overall outcomes. In this review, an overview of the recent advances of immunotherapy in the management of CSCC in the anatomical head and neck region is provided, with a focus on advanced presentations.

Systemic Relapse in a Young Adult Patient with Primary CNS Diffuse Large B-Cell Lymphoma.

Primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) is a rare form of non-Hodgkin's lymphoma, characterized by an aggressive disease course. While CNS relapse is common, systemic relapse is rare with no consensus on optimal treatment. This paper presents an unusual case of advanced PCNS-DLBCL with systemic relapse, including adrenal gland involvement. A review of the existing literature and a discussion on the management of systemic relapse in PCNS-DLBCL is also provided.

Transient left ventricular dysfunction following chimeric antigen receptor T-cell-mediated encephalopathy: A form of stress cardiomyopathy.

Chimeric antigen receptor (CAR) T-cell therapy represents a new strategy in treating lymphoid malignancies, such as relapsed-refractory diffuse large B-cell lymphoma (DLBCL). Several toxicities including cytokine release syndrome (CRS), neurotoxicity, and cardiovascular toxicity have been linked to CAR T-cell therapy. Transient impairment in left ventricular systolic function is described after CAR-T, however, the mechanism remains poorly understood. This paper reports the clinical presentation and outcome of two patients with relapsed-refractory DLBCL who experienced encephalopathy and CRS following CAR T-cell therapy and developed transient left ventricular dysfunction consistent with stress cardiomyopathy.

Managing Nutrition Impact Symptoms in Cancer Cachexia: A Case Series and Mini Review.

Malnutrition is common in cancer patients and can occur throughout a patient's disease course. The contributors to the clinical syndrome of cancer cachexia are often multifactorial, and produced by the cancer and associated pro-inflammatory response. Since cancer cachexia is a multifactorial syndrome, a multimodal therapeutic approach is ideal. A key component of therapy is identifying and managing symptom barriers to adequate oral intake, known as nutritional impact symptoms (NIS). NIS are associated with reduced intake and weight loss in patients with advanced cancer, and aggregate NIS are a predictor of survival in patients with Head and Neck Cancer and in patients undergoing surgery for esophageal cancer. Currently, there are no guidelines regarding the specific management of NIS in oncology patients. Experience from specialist centers suggest relatively simple assessments and inexpensive interventions are available for the diagnosis and treatment of NIS. We present three patient cases from a cachexia clinic, where NIS management decreased symptom burden and improved clinical outcomes such as weight and physical performance.

Recombinant activated factor VII in a patient with intracranial hemorrhage and severe thrombocytopenia.

Hemorrhage in patients with hematologic malignancies is often difficult to manage as many of these patients also have coagulopathy and thrombocytopenia of varying severity. Recombinant factor VIIa is a FDA-approved agent for management of bleeding in hemophilia patients with inhibitors. Use of recombinant FVIIa has also been used as a last resort in various clinical settings such as trauma, alveolar hemorrhage, gastrointestinal bleeding, and intracranial hemorrhage for control of bleeding with variable outcomes. This paper presents a case of recombinant FVIIa administration in a patient with multiple myeloma and profound transfusion refractory thrombocytopenia suffering from traumatic subdural hematoma.

Severe immune thrombocytopenia induced by a single dose of nivolumab in a patient with advanced non-small cell lung cancer.

Nivolumab-induced immune thrombocytopenia (ITP) is a rare process with few reported cases. We present a 67-year-old man with advanced non-small cell lung cancer who was hospitalized with severe thrombocytopenia. Physical exam was notable for petechiae across his chest and extremities as well as bullae in his oral cavity. The patient initially received high-dose glucocorticoids and intravenous immuno - globulin, but did not respond to treatment. He was then started on weekly rituximab and after three doses, there was complete resolution of his thrombocytopenia. Altogether, his presentation was an extreme case and rare side effect of immune checkpoint therapy, known as nivolumab-induced ITP. Diagnosis of nivolumab-induced ITP is challenging given the lack of specific testing and a wide differential diagnosis. There are few cases reporting severe ITP following nivolumab treatment. We highlight the importance of recognizing and treating this rare complication of immunotherapy.

Primitive neuroectodermal tumor of the uterus: Excellent clinical response following a multimodal treatment approach.

We present a case report of a patient with uterine primitive neuroectodermal tumor (PNET). The patient underwent surgical management followed by pelvic radiation and intravaginal brachytherapy. Following a stable interval, the patient was found to have new onset spinal, pulmonary, and adrenal metastatic disease. She was subsequently started on high dose carboplatin and etoposide. An interval reduction of her metastatic disease was observed after three cycles. We conclude that a multimodal approach, including platinum-based adjuvant chemotherapy with etoposide, can be effective in patients who present with residual or recurrent disease after surgical and radiation therapy. However, more robust studies with longer follow-up periods will be needed to establish a consensus regarding effective treatment options.