Explore the vast range of titles available.

During the past decade, immune checkpoint inhibitors (ICIs) have revolutionized the landscape of cancer treatment. IC I - related side effects occur via direct overactivation of the immune system, and patients can experience symptoms akin to autoimmune disease. These symptoms can range in severity from mild to severe and can be fatal. Advanced practice providers require a heightened awareness of the wide range of immune-related adverse events that can occur with ICI therapy.

Purpose The aim of this study is to better characterize the clinical characteristics and outcomes of patients diagnosed with Immune checkpoint Inhibitor (ICI) pneumonitis and propose predictive models. Patients and methods Patients diagnosed with ICI pneumonitis at Mayo Clinic from 2014 to 2022 were studied. All cases were independently reviewed by our pulmonology specialist (A.E.) to confirm the appropriate diagnosis. The grading of pneumonitis was defined in accordance with ASCO guidelines (Schneider et al. in J Clin Oncol 39(36):4073–4126, 2021. https://doi.org/10.1200/JCO.21.01440 ). Predictive modeling was performed using gradient boosting machine learning technology, XGBoost (Chen in 1(4):1, 2015), to conduct binary classification and model reverse engineering using Shapley statistics (Lundberg and Lee in Adv Neural Inf Process Syst 30, 2017). Results One hundred and seventy patients with ICI pneumonitis were included (median age 67; IQR 59, 75). Median overall survival was 2.3 years (95% CI: 1.8, NR). A higher grade of ICI pneumonitis was associated with inferior survival (HR 5.85, 95% CI: 2.27, 15.09; p  < 0.001). Patients who were rechallenged with immunotherapy had significantly improved hazard of survival compared to patients not rechallenged (HR 0.37, 95% CI: 0.21, 0.68; p  = 0.001). Risk of death from ICI pneumonitis prior to starting immunotherapy was modeled with an area under the curve of the receiver operator characteristic (AUC-ROC) of 0.79 with the most contributory features including peripheral blood lymphocyte count, oxygen dependence, pulmonary function testing, and PD-L1 expression. Conclusion The presentation of ICI pneumonitis is highly variable, and outcomes are dependent on severity, but favor grade 2 disease when patients are rechallenged with immunotherapy. However, using commonly available clinical data, we can accurately identify patients at high risk of death from ICI pneumonitis. Further effort is needed to produce clinical models able to provide clinician decision support when evaluating patients with ICI toxicities and considering ICI rechallenge.

BackgroundCheckpoint inhibitors continue to be used for a wide variety of oncologic and hematologic indications. Early recognition and intervention is crucial to prevent significant morbidity and/or mortality from immune related adverse events (irAE’s). Physicians and APPs outside of hematology/oncology practices are generally not familiar with these types of side effects which may lead to treatment delays, and inappropriate management. We recently identified this as a gap in continuity of care amongst patients undergoing CPI therapy for their malignancy, and therefore developed a CPI acute care outpatient clinic, designed to meet this need.MethodsStarting April 2020, we developed an CPI focused clinic led by 3 APPs to provide outpatient irAE management 5 days a week. Three types of needs were identified: acute (within 24 hours), post hospitalization (within 48 hours of discharge), and long term follow-up (high grade irAE).ResultsFrom April 24-August 24, 2020 our CPI clinic had a total of 50 visits (30 unique patients). Given that many patients to our practice are from > 2 hours away, as well as the constraints of the current pandemic, visits were conducted as in person, video consult (telemedicine), or phone. The most common regimens for patients were PD-1 alone (10), PD-1 + targeted (7), dual CPI (6), PD-1 + chemotherapy, and clinical trial, PD-L1 alone, PD-L1 + chemotherapy (1 each). The top three types of malignancies seen were melanoma (7), lung (6) and gynecological (4). The most common irAE referral reason was hepatitis (8), diarrhea/colitis (6) and thyroiditis (4). Only three patients (10%) required higher level care (i.e ED or admission) than was able to be provided in the clinic. Twenty-two patients (73%) required steroids as their initial treatment for irAE, with 4 patients (13%) requiring referral to other specialties. Twelve patients (40%) presented with ≥2 irAE’s at the time of being seen in clinic.ConclusionsHerein we present early data from an acute care APP led CPI outpatient clinic. Most patients required initiation of steroids for their irAE, however only a small majority required higher level of care and were able to be managed as an outpatient. We acknowledge that while our cohort of patients is small, it does provide early evidence of the utility of a CPI acute care clinic and additional hypothesis generating clinical questions.Ethics ApprovalThis study was approved by the institutional review board at Mayo Clinic

Purpose Lung cancer in non-smoking women is a distinct entity, but few studies have examined these patients’ healthcare-related experiences. Methods Women with lung cancer and with no smoking history underwent a face-to-face semi-structured, audio-recorded interview that was analyzed with a qualitative inductive approach. Results Twenty-three patients were interviewed, and three themes emerged. The first theme centered on a delay in cancer diagnosis. One patient described, “The whole initial diagnostic process just fills me with rage… I didn’t actually get my Tarceva® until the last week in April.” Second, the diagnosis of lung cancer seemed especially challenging in view of patients’ non-smoking history and otherwise good health; these factors seem to have contributed to the diagnostic delay. One patient explained, “Well, I was just so adamant that I didn’t like smoking… maybe if I had been a smoker, they [the healthcare providers] would’ve been more resourceful.” Finally, the stigma of a smoking-induced malignancy was clearly articulated, “Yeah. Because it’s a stigma, and I had read that, too -- people go, ‘Well, it’s your own damn fault because you were a smoker.’” Conclusions Non-smoking women with lung cancer appear to endure a long trajectory from symptoms to cancer diagnosis to the initiation of cancer therapy. An awareness and acknowledgement of this long trajectory might help healthcare providers render more compassionate cancer care to these patients.

BackgroundIn May 2024, the FDA approved tarlatamab, a Delta-like ligand (DLL3)/CD3-targeted bispecific T-cell engager, for patients with extensive-stage small cell lung cancer (SCLC) with disease progression following platinum-based chemotherapy and at least one other prior line of therapy. We aim to examine the cellular immune cell profile changes seen in patients receiving this therapy in standard-of-care (SOC) practice.MethodsPatients who received tarlatamab at Mayo Clinic Rochester consented to research blood. Immune phenotyping was performed on whole blood by flow cytometry and analyzed by Kaluza. Data analysis was performed with Excel and PRISM.ResultsThirteen patients with a median age 64 years (range 41-80) who were treated and evaluable for clinical response were included, 53% were women. All had a history of tobacco use.Nine (69%) patients had progressive disease (PD) after a median of 2 cycles, whereas 4 patients had partial response (PR) or stable disease (SD) after at least 2 cycles and remain on therapy (no-PD). Compared to the no-PD group, those whose disease PD early had higher levels of exhausted CD8 T cells at baseline (PD1+TIGIT+CD57+, PD vs no-PD, cells/µL: 17.4±5.6, 7.6±2.6, p=0.006). Interestingly, a CD8 TIGIT+PD1negCD57neg population was also identified which was higher at baseline (PD vs no-PD, cells/µL: 21.5±16.9, 12.2±5.33, p=0.039) and decreased significantly for the PD group from baseline to day 7 (21.5±16.9 to 9.30±10, p=0.039; figure 1A). This population was found to have a different functional profile than the exhausted phenotype in other solid tumors and its role in small cell lung cancer has not been defined. At day 7, compared to the no-PD group, the PD group also had a high level of B-cells (PD vs no-PD, cells/µL: 10.3±15, 4.07±1.83, p=0.027), classical monocytes (PD vs no-PD, cells/µL: 365±279, 226±121, p=0.035), and immunosuppressive monocytes (CD14+HLA-DRneg monocytes, cells/µL: 119±93, 33±42, p=0.05). In addition, the no-PD group had a statistically significant decrease from baseline to day 7 in intermediate monocytes (32.5±7.9 to 17±2.6, p=0.049; figure 1B).ConclusionsIn this study investigating the SOC outcomes of tarlatamab, early PD was associated with higher presence of exhausted CD8 T cells, B cells, and immunosuppressive monocytes. Analysis of additional patients will be shared at SITC meeting.Abstract 844 Figure 1ACD8 T cell phenotype associated with clinical response[Image Omitted. See PDF.]Abstract 844 Figure 1BMonocyte phenotype associated with clinical response[Image Omitted. See PDF.]