9535 Background: Metastatic UM is associated with a median overall survival (OS) < 1 year (yr) and overall response rate (RR) to ICI < 18%. SF3B1 mut UM represent a clinically unique subset of UM, distinct from BAP1 mut disease, characterized by aberrant spliceosome machinery which may result in increased neoantigen presentation, increased immunogenicity, and sensitivity to ICI. To assess these hypotheses, we performed a multicenter retrospective analysis to assess the natural history and response to ICI in patients (pts) with SF3B1 mut UM. Methods: Patients were identified from institutional databases and the AACR Project GENIE Consortium. Data collected included: baseline and recurrent disease characteristics, molecular characteristics, treatments received, treatment response, and vital status. Efficacy endpoints included investigator assessed RECIST RR and OS. Results: 58 pts with deleterious SF3B1 mutations were identified: 56 R625; 1 D781G; 1 G742D. Median age at diagnosis (dx) was 52 (range, 14-87). 50% were female. 49 pts developed distant metastases. The median time from initial dx to metastasis was 6.1 years (yrs; range, 0.9 to 26.7). Initial metastatic sites (n = 48) were: liver-only (52%); non-liver-only (29%); mixed liver and non-liver disease (19%). The most common initial metastatic sites were: liver (71%), lung (29%), soft tissue (13%), lymph node (8%), and bone (4%). The median OS for all pts from time of metastasis was 3.9 years (95% confidence interval (CI), 2.3-6.2) with OS for pts with non-liver only disease at 6.2 yrs vs those with liver-only or mixed disease at 3.4 yrs (hazard ratio = 2.12, p = 0.14). 1-year OS rate from time of metastasis was 94% (95% CI, 0.86-0.99). 34 pts received ICI for metastatic disease at which time 27% had received a prior systemic therapy (median, 0; range, 0-3) and 35% had received a prior hepatic regional therapy (median, 0; range, 0-6). 15 pts received single-agent anti-PD1; 4 received ipilimumab alone; 15 received dual ICI. 10 pts received ICI with concurrent hepatic regional tx. Best response among 33 evaluable pts were: 9% partial response; 39% stable disease; 52% progressive disease. Median OS from ICI initiation was 20.2 months (95% CI, 13.1-27.4). 1-year OS from ICI initiation was 74% (95% CI, 0.59-0.90). Conclusions: SF3B1 mut UM is characterized by later development of metastases, more common involvement of extrahepatic sites, and longer OS when compared with historical datasets of molecularly unselected UM. Although a modest RR to ICI was observed, the median OS and 1-year survival rate post-ICI are numerically superior to historical controls. Given the more indolent course of SF3B1 mut UM, stratification by SF3B1 status should be included in future clinical trials.
Background: ICI are widely used in the treatment of various cancer types. It has been hypothesized that ICI could confer an increased risk of severe acute lung injury or other complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We analyzed data from 113 patients with laboratory-confirmed COVID-19 while on treatment with ICI without chemotherapy in 19 hospitals in North America, Europe, and Australia. Data collected included details on symptoms, comorbidities, medications, treatments and investigations for COVID-19, and outcomes (hospital admission, ICU admission, and mortality). Results: The median age was 63 years (range 27–86); 40 (35%) patients were female. Most common malignancies were melanoma (n=64, 57%), non-small cell lung cancer (n=19, 17%), and renal cell carcinoma (n=11, 10%); 30 (27%) patients were treated for early (neoadjuvant/adjuvant) and 83 (73%) for advanced cancer. Most patients received anti-PD-1 (n=85, 75%), combination anti-PD-1 and anti-CTLA-4 (n=15, 13%), or anti-PD-L1 (n=8, 7%) ICI. Comorbidities included cardiovascular disease (n=31, 27%), diabetes (n=17, 15%), and pulmonary disease (n=14, 12%). Symptoms were present in 68 (60%) patients; 46 (68%) had fever, 40 (59%) cough, and 23 (34%) dyspnea. Overall, ICI was interrupted in 58 (51%) patients. At data cutoff, 33 (29%) patients were admitted to hospital, 6 (5%) to ICU, and 9 (8%) patients died. COVID-19 was the primary cause of death in 7 patients, 3 of whom were admitted to ICU. Cancer types in patients who died were melanoma (2), non-small cell lung cancer (2), renal cell carcinoma (2), and others (3); all (9) patients had advanced cancer. Administered treatments were oxygen therapy (8), mechanical ventilation (2), vasopression (2), antibiotics (7), antiviral drugs (4), glucocorticoids (2), and anti-IL-6 (2). Of all hospitalized patients, 20 (61%) had been discharged and 4 (12%) were still in hospital at data cutoff. Conclusion: The mortality rate of COVID-19 in patients on ICI is higher than rates reported for the general population without comorbidities but may not be higher than rates reported for the cancer population. Despite these preliminary findings, COVID-19 patients on ICI may not have symptoms and a proportion may continue ICI. Correlative analyses are ongoing and will be presented. Citation Format: Aljosja Rogiers, Carlo Tondini, Joe M. Grimes, Megan H. Trager, Sharon Nahm, Leyre Zubiri, Neha Papneja, Arielle Elkrief, Jessica Borgers, April Rose, Johanna Mangana, Michael Erdmann, Ines Pires da Silva, Christian Posch, Axel Hauschild, Lisa Zimmer, Paola Queirolo, Caroline Robert, Karijn Suijkerbuijk, Paolo A. Ascierto, Paul Lorigan, Richard Carvajal, Osama E Rahma, Mario Mandala, Georgina V. Long. Clinical characteristics and outcomes of coronavirus 2019 disease (COVID-19) in cancer patients treated with immune checkpoint inhibitors (ICI) [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr S02-01.
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