Objectives: C5 inhibitors such as eculizumab and ravulizumab are the first-line treatment in the management of paroxysmal nocturnal hemoglobinuria (PNH). However, some patients develop novel symptoms as part of their treatment with eculizumab, and the disease is termed as eculizumab refractory PNH. The aim of this study was to conduct a systematic review on the available treatment modalities for the management of eculizumab refractory PNH. Methods: Two authors independently searched two databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 70 studies were obtained: 4 out 70 studies were found to meet the inclusion criteria. Results: Four studies were found to meet the inclusion criteria of our study. Two studies were published in 2021 and two studies were published in 2020. All four studies were multicenter clinical trials. Two studies were phase III clinical trials, one study was a phase II clinical trial, and one study was a phase I clinical trial. Two studies were about pegcetacoplan, one was about danicopan, and one was about iptacopan. Conclusion: Based upon the findings of our systematic review, we recommend an individualized treatment plan based on the mechanism of eculizumab refractoriness and the mechanism of PNH breakthrough. This recommendation is subject to the available resources and clinical expertise available at different hospitals. More studies using study designs such as randomized controlled trials comparing multiple drugs should be performed to accurately assess the different medications and aid in designing guidelines of the management of eculizumab refractory PNH. Level of evidence: Level I

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81 Background: The adoption of immunotherapy has led to a paradigm shift in the treatment of many advanced stage malignancies. Patients with durable long term survival under cancer immunotherapy have begun to emerge. Circulating memory immune T and B-cells play a key role in the anamnestic response to future similar antigen exposure and may contribute to durable cancer immunotherapy response and benefits in patients with irAE. We hypothesized that there is increased median overall survival (mOS) in patients who had irAE under CPI therapy. Methods: We conducted a retrospective analysis with an IRB-approved study protocol of adults treated between 2011-2019 at the West Virginia University Cancer Institute, with a histopathologic diagnosis of melanoma or lung cancer, who had received CPI therapy. We collected data on demographics, histology, stage at diagnosis, immunotherapy type used, irAE and its grade, and days from immunotherapy initiation to death. Patients were stratified by irAE status and CPI rechallenge status following irAE. Results: Demographics were similar between the irAE and non-irAE groups within both cancer types. A total of 229 lung and 114 melanoma cancer patients had received CPI. Overall, there were 105/343 (30.6%) cases of irAE found of any grades: 27.5% of lung and 37.7% of melanoma patients developed irAE. The mOS for the non-irAE cohort group was 299 days, which was significantly worse than the irAE cohort (mOS not met, Log-rank, p < 0.0001). Within the irAE cohort, there was no significant survival difference between the non-rechallenged and rechallenged groups (Log-rank p = 0.6150). Conclusions: Our findings identified significantly improved survival outcomes among lung cancer/melanoma patients treated with CPI who developed irAE, including those who were rechallenged after irAE, compared to those who had no irAE. Patients who were CPI-rechallenged after irAE had comparable survival outcomes compared to those without rechallenge. Further multi-center validation studies and prospective studies are warranted to further confirm these findings and help guide clinical management in patients who experience CPI irAE.

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e23012 Background: Fellowship programs use a variety of continuity clinic models including general, disease/system specific, or both. The longitudinal timing also varies from 6-months, 1-year, or the entirety of fellowship. At WVU, we use a 6-month disease specific model where fellows rotate with a specific attending. Given the increasing complexity of care for patients with oncologic diagnoses, we sought to establish a general continuity clinic within an academic cancer institute to model the skills needed to effectively transition to independent practice. Additionally, we proposed to identify key elements that make for a meaningful continuity clinic experience. Methods: We created a 42 question, anonymous online survey comparing general clinic to the disease specific clinic and administered it to our current 2nd and 3rd year fellows. Independent variables were Likert-scale ratings (1=strongly disagree, 2= disagree, 3=neutral, 4=agree, 5=strongly agree) on four main themes: patient characteristics, clinic operations, preceptor characteristics, and educational value. Results: Seven out of seven fellows responded. The majority of them answered that 1 new patient and 4 return patients were “just right” per half day of general clinic, while 1-2 new patients and 5 or more return patients were “just right” per half day of disease specific clinic. Within the general clinic, the number of patients with lung, GU, and GI oncology was noted as “just right” while breast and other (e.g., CNS, head and neck, sarcoma) were identified as “too few”. Table shows a sample of questions asked and differences among the two clinics. The most evident disparity was autonomy of patients. A weekly, multispecialty planning session was also rated highest in terms of educational value for general clinic. Conclusions: We demonstrated a general continuity clinic can be successfully implemented within an academic cancer center. While there are pros and cons to both types, several key characteristics to a meaningful continuity clinic experience were identified including: adequate ratio of new and return patients, wide variety of diagnoses, increased autonomy and ownership of patients, consistent preceptor and support staff, and weekly planning session for increased preparation and educational value.[Table: see text]