Early discontinuation of immune checkpoint inhibitor therapy prior to disease progression in patients with metastatic non-small cell lung cancer: a survival analysis.

Introduction: Limited survival data are available for patients with metastatic non-small cell lung cancer (mNSCLC) who stop immune checkpoint inhibitor therapy (ICI) early for reasons other than progression of disease (POD), such as immune-related adverse events (irAEs). Methods: We conducted a retrospective observational study of all patients with mNSCLC treated with ICIs, with or without combination chemotherapy, at 3 Mayo Clinic sites between 2011 and 2022. Separate analyses were conducted at 6- and 12-month intervals. Patients who discontinued ICI due to POD prior to these time points were excluded from the analysis. Results: A total of 246 patients with stage IV NSCLC used ICIs. Patients were then excluded if they had experienced POD prior to 6 or 12 months, resulting in 81 and 63 patients, respectively, for each timepoint. Sixty-four patients continued treatment beyond 6 months and were found to have longer progression-free survival (PFS) compared to the 17 patients who discontinued treatment (22.8 months vs 11.8 months, P =1.1E-04), as well as a significant increase in overall survival (OS) (33.9 months vs 14.4 months, P =7.2E-08). Forty patients continued treatment beyond 12 months and had longer PFS compared to the 23 patients that discontinued treatment (27.9 months vs 14.8 months, P =1.1E-04), as well as a significant increase in OS (39.7 months vs 18.0 months, P =2.0E-07). The most common reason for ICI discontinuation was irAEs. Other common reasons for stopping ICI were non-irAEs and stable disease. At both time points, 12 patients continued or restarted ICI after experiencing an irAE, and 2 patients experienced recurrent/new grade 1-2 irAEs. More patients continued/rechallenged with ICI after experiencing an irAE in the groups that continued ICI compared to those that discontinued ICI. Conclusions: Patients with mNSCLC and no POD who continued ICI beyond 6 months and 12 months, experienced significantly increased PFS and OS compared to patients who discontinued ICI, with larger increases in those who continued ICI past 12 months. Oncology providers should discuss the survival benefits of continuing ICI and offer support to overcome obstacles to continuation of treatment, if possible, particularly management of grade 1 and 2 irAEs.

Metastatic Non-Small Cell Lung Cancer Mimicking Metaplastic Breast Cancer: A Case Report.

NGS used to diagnose and treat NSCLC patient with initial concern for metaplastic breast cancer.

Severe Cytokine Release Syndrome and Hemophagocytic Lymphohistiocytosis (HLH)-Like Syndrome Following Administration of Combined Brentuximab Vedotin and Nivolumab for Recurrent Classical Hodgkin Lymphoma: A Case Report.

Brentuximab vedotin (BV) and nivolumab are increasingly utilized as a novel regimen in patients with relapsed/refractory classical Hodgkin lymphoma (cHL). A 26-year-old male presented to the hospital with refractory diabetic ketoacidosis and multiple electrolyte abnormalities, 9 days after the first dose of brentuximab vedotin and nivolumab for recurrent classical Hodgkin lymphoma. During his hospitalization, he developed multi-organ failure. His workup showed elevated cytokine levels concerning severe cytokine release syndrome (CRS) and hemophagocytic lymphohistiocytosis (HLH)-like syndrome. Despite treatment with CRS- and HLH-directed therapies, his clinical status deteriorated due to ongoing multifactorial shock and worsening multi-organ dysfunction, and comfort care measures were eventually pursued. To our knowledge, there have been no other cases reported of HLH-like syndrome after the combination of BV and nivolumab in patients with cHL. This case of a fatal adverse event following one dose of BV and nivolumab underscores the vital need for close monitoring of patients receiving this treatment regimen.

Immune-Related Adverse Events in Patients with Lung Cancer.

PURPOSE OF REVIEW: Immune checkpoint inhibitors (ICI) have been widely adopted for the treatment of lung cancer since receiving first U.S Food and Drug Administration (FDA) approval in 2015. However, along with their use, the occurrence of immune-related adverse events (irAEs) has presented a challenge for both patients and oncology providers. In this manuscript, we reviewed the clinical trials that led to the approval of ICI by the FDA for the treatment of lung cancer between 2015 and 2023 to establish the frequency of irAEs in this patient population. Among the adverse events associated with ICI, we focused on the most common and relevant ones, including hypothyroidism, pneumonitis, diarrhea/colitis, skin rash, and hepatitis. RECENT FINDINGS: We thoroughly examined the available literature, including society guidelines concerning these complications, to discuss various aspects such as their pathophysiology, epidemiology, diagnostic process, grading system, and clinical management. Additionally, we explored the association between irAEs and disease response. The management of irAEs is a crucial aspect of oncologic care, particularly due to their potential to cause severe and life-threatening clinical manifestations. We present each pertinent aspect in a concise and organized manner to provide guidance and assistance to oncology providers managing these patients in both outpatient and inpatient settings.

Brief report: risk stratification following curative therapy for stage I NSCLC.

Introduction: Surveillance with computed tomography (CT) imaging following curative treatment of stage I non-small cell lung cancer (NSCLC) is important to identify recurrence or second primary lung cancers (SPLC). The pattern and risks of recurrence following curative therapy and optimal duration of surveillance scans remain unknown. The objective of our study is to assess the pattern of recurrence and development of SPLC to risk stratify patients with stage I NSCLC following curative therapy. Methods: We identified 261 patients who received curative therapy for stage I NSCLC at Mayo Clinic Florida. Data was collected on clinical and demographic features including gender, smoking history, stage, treatment, histologic subtype, and tumor grade. Kaplan-Meier method was used to evaluate the disease free survival (DFS). Cox proportional hazard model was used to identify risk factors for recurrence. Results: Negative tobacco history and stage IA tumors were associated with significantly prolonged DFS after adjusting for co-variates (p=0.001 and p=0.005). Univariate Cox proportional hazards model identified tobacco history and stage 1B as risk factors for recurrence with unadjusted hazard ratio (HR) of 2.8 and 2.0, respectively. After adjusting for covariates, only stage IB was statistically significant predictor of recurrence with a hazard ratio of 2.1 (Confidence Interval (CI) 95% 1.2-3.6; p=0.007). Conclusions: An individualized approach that considers risk factors of stage and smoking history may be useful in determining whether to continue annual CT surveillance after five years post curative therapy for stage I NSCLC.

Humoral Responses After SARS-CoV-2 mRNA Vaccination and Breakthrough Infection in Cancer Patients.

OBJECTIVE: To evaluate the magnitude of humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in patients with cancer receiving active therapies. PATIENTS AND METHODS: Patients 18 years or older in whom SARS-CoV-2 spike antibody (anti-S Ab) levels were measured after 2 doses of SARS-CoV-2 mRNA vaccines were included. Patients with prior coronavirus disease 2019 (COVID-19) infection or receiving other immunosuppressive therapy were excluded. RESULTS: Among 201 patients who met the criteria, 61 were immunocompetent, 91 had a hematologic malignancy, and 49 had a solid malignancy while receiving treatments associated with cytopenia, including chemotherapy or cyclin-dependent kinase 4 and 6 inhibitors. A significantly greater proportion of immunocompetent patients (96.7% [59 of 61]) had anti-S Ab titers of 500 U/mL or greater compared to patients with hematologic (7.7% [7 of 91) and solid (55.1% [27 of 49]) malignancy (P<.001). Despite 2 doses of SARS-CoV-2 mRNA vaccines, 52.7% of patients with hematologic malignancy (48 of 91) and 8.2% of those with solid malignancy (4 of 49) receiving cytopenic therapy had no seroconversion (spike antibody titers <0.8 U/mL). Two patients subsequently had development of breakthrough COVID-19 infection after full vaccination. CONCLUSION: A substantial proportion of patients with hematologic and solid malignancies receiving chemotherapies and CDK4/6i had poor humoral responses after SARS-CoV-2 mRNA vaccination. Our study adds to a growing body of literature suggesting that immunosuppressed patients have a suboptimal humoral response to COVID-19 vaccination. Our study also underscores the importance of assessing antibody response after COVID-19 vaccines in these vulnerable patients.

Hemophagocytic Lymphohistiocytosis for the Internist and Other Primary Care Providers.

Hemophagocytic lymphohistiocytosis (HLH) syndrome is a hyperinflammatory state that leads to life-threatening, disproportionate activation of the immune system and may be confused for and concomitantly exist with sepsis. However, its treatment differs from sepsis, requiring early initiation of immunosuppressive treatment. While HLH syndrome is more commonly diagnosed in children, internists and other primary care providers must be familiar with the diagnosis and treatment of adult patients with HLH in the hospital and outpatient setting. In this article, we review the essentials that an internist and other primary care providers managing adult HLH patients should know.

Temporal metabolic response to mRNA COVID-19 vaccinations in oncology patients.

BACKGROUND: mRNA COVID-19 vaccines are known to provide an immune response seen on FDG PET studies. However, the time course of this metabolic response is unknown. We here present a temporal metabolic response to mRNA COVID-19 vaccination in oncology patients undergoing standard of care FDG PET. METHODS: 262 oncology patients undergoing standard of care FDG PET were included in the analysis. 231 patients had at least one dose of mRNA COVID-19 vaccine while 31 patients had not been vaccinated. The SUVmax of the lymph nodes ipsilateral to the vaccination was compared to the contralateral to obtain an absolute change in SUVmax (ΔSUVmax). RESULTS: ΔSUVmax was more significant at shorter times between FDG PET imaging and COVID-19 mRNA vaccination, with a median ΔSUVmax of 2.6 (0-7 days), 0.8 (8-14 days), and 0.3 (> 14 days), respectively. CONCLUSION: Consideration should be given to performing FDG PET at least 2 weeks after the COVID-19 vaccine.

Asymptomatic coronavirus disease 2019 mimicking metastatic breast cancer on positron emission tomography/computed tomography imaging.

A 55-year-old asymptomatic woman with newly diagnosed, locally advanced breast cancer undergoing routine staging with 2-deoxy-2[18F]fluoro-d-glucose positron emission tomography/computed tomography was found to have multiple hypermetabolic pulmonary nodules on imaging that were concerning for metastatic disease. However, further workup with dedicated chest computed tomography imaging demonstrated multiple bilateral, peripheral nodular lesions with peripheral ground-glass opacity, predominantly in the lower lung zone, that were suspicious for coronavirus disease 2019. The patient ultimately was diagnosed with coronavirus disease 2019 based on detection of viral ribonucleic acid via polymerase chain reaction. Follow-up chest computed tomography scan obtained after 27 days showed complete resolution of the lung lesions. In the setting of a global pandemic, a high index of suspicion for coronavirus disease 2019 in cancer patients is warranted, not only to enable early identification and treatment of a potentially aggressive infection but also to prevent misdiagnosis of metastatic disease.

Pre-diagnosis major life stressors and breast cancer outcomes.

PURPOSE: While the association between diagnosis of breast cancer and post-diagnosis psychological distress has been well documented, data regarding pre-diagnosis psychological distress in the breast cancer population are limited. Here, we assessed pre-diagnosis major life stressors and breast cancer outcomes, namely stage of disease and choice of surgery, in a single-center population. METHODS: Patients with newly diagnosed clinical stage 0-3 breast cancer seen at Mayo Clinic Florida between June 11, 2018, and October 7, 2019, were administered voluntary telephone surveys to assess major life stressors during the 24 months preceding their cancer diagnosis. Subsequent clinical outcomes of cancer stage at diagnosis and surgical treatment were obtained through retrospective chart review. Study subjects who had experienced major life stressors and those who had not were compared using Chi-square tests. RESULTS: Of 222 patients who were included, 51.3% reported experiencing a major life event before breast cancer diagnosis. 43.9% of these patients endorsed family-related stress. 21.1% had experienced multiple stressors. 1.8% described financial stress. Although more patients in the group with pre-diagnosis stress had carcinoma in situ (21.1% versus 13.0%, p = 0.11) and fewer had stage T1/T2 disease (64% versus 73.1%, p = 0.14) than in the group without stress, these differences were not statistically significant. More patients with pre-diagnosis stress chose mastectomy (34.2% versus 22.2%, p = 0.048). CONCLUSIONS: Psychological distress is prevalent prior to breast cancer diagnosis and may merit early intervention. While additional study in diverse populations is needed, current data suggest possible associations between pre-diagnosis psychological distress and surgical decision making, specifically mastectomy.