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Despite their anti-tumor efficacy, immune checkpoint inhibitors (ICIs) are associated with a variety of immune-related adverse events (irAEs). Grade ≥ 2 irAEs require ICI discontinuation. The decision to resume ICI treatment often remains challenging.We retrospectively studied 1051 adult patients with stage IV non-small cell lung cancer (NSCLC) treated with ICIs at a single institution between January 2015 and December 2020, and identified 99 (9.4%) patients with grade≥2 irAEs necessitating treatment interruption. Forty patients underwent retreatment (rechallenged group), while 59 discontinued the treatment (discontinued group).Baseline characteristics of patients in the 2 groups were similar. Initial irAEs were less severe in the rechallenged group. After rechallenging, 24 of 40 (60%) patients had recurrence of the same or de-novo irAEs. Twenty (50%) developed second grade≥ 2 irAEs. No grade 4 irAE or irAE-related death occurred after rechallenging. Using multivariate analysis, no statistically significant differences in overall survival (OS) (HR: 1.10, 95% CI: 0.57-2.15, P = .77) or progression-free survival (PFS) (HR: 0.87, 95% CI: 0.45-1.71, P = .69) were noted between the 2 groups, while the best objective response prior to the initial irAEs was the only variable affecting OS and PFS.Rechallenge was associated with a relative high risk of second grade≥ 2 irAEs. The risk was less if the initial irAEs were resolved. No differences were seen in survival outcomes of patients who had ICI rechallenge and those who did not. Permanent ICI discontinuation is an appropriate strategy after grade≥ 2 irAEs, especially severe irAEs.

e14547 Background: Eighty percent of nonmelanoma skin malignancies are basal cell carcinomas (BCC). Metastasis in BCC is about 0.0028 to 0.55. Diagnosis and treatment of metastatic BCC is challenging due to its rarity. In approximately 85% of metastatic BCC, the most common metastatic organs are lymph nodes. Methods: We reviewed 31 skin BCCs with bone metastasis in the past 60 years and 10 observation studies on the efficacy of Sonic hedgehog inhibitors (SHHis). We focused on treatment and outcome of 31 metastatic BCC. Results: The main treatment option was surgery and radiotherapy is a palliative option. Among chemotherapeutic and immunotherapeutic agents, SHHis (e.g. vismodegib and sonidegib) appear to be effective, with reported ORR of 43-100%, and CRR range of 3%-54%. In locally advanced BCCs, vismodegib shows 10 times higher CRRs compared to sonidegib, although ORRs were similar. In metastatic BCC, overall response to vismodegib was three times higher. The common adverse effects of SHHis limit their administration. Conclusions: BCC is a common skin neoplasm that rarely demonstrates metastasis. Among the chemotherapy agents administered, vismodegib appears promising.[Table: see text]

e21173 Background: Despite their anti-tumor efficacy, immune checkpoint inhibitors (ICIs) are associated with a variety of immune-related adverse events (irAEs). Grade ≥2 irAEs require ICI discontinuation. The decision to resume ICI treatment often remains challenging. Methods: We retrospectively studied 1051 adult patients with stage IV NSCLC treated with ICIs at West Cancer Center between January 2015 and December 2020. 99 (9.4%) patients with grade≥2 irAEs necessitating treatment interruption were identified. 40 patients underwent retreatment (rechallenged group), while 59 discontinued treatment (discontinued group). All patients were rechallenged with the initial ICI. Results: The baseline characteristics of patients in the two groups were similar in terms of age, gender, ethnicity, ECOG, smoking status, cancer histology, type of ICI, and PD-L1 status. No differences in types of irAEs or timing of the initial irAEs were seen. Initial irAEs were less severe in the rechallenged group, with fewer grade 3 irAEs (20% vs. 62.7%, p < 0.001), no grade 4 irAEs (0% vs. 6.8%, p < 0.001), less IV corticosteroid use (2.5% vs. 23.7%, p = 0.01), and less frequent hospitalizations for irAEs (7.5% vs. 42.4%, p < 0.001). After rechallenging, 24 of 40 (60%) patients had recurrence of the same or de-novo irAEs. 20 (50%) developed second grade≥2 irAEs with 13 (32.5%) grade 2, and 7 (17.5%) grade 3. No grade 4 irAE or irAE-related death occurred after rechallenging. Among the 24 patients with second irAEs, 6 (25%) still had residual grade 1 irAEs upon rechallenging, while none of the 16 patients without second irAEs had residual irAEs (p = 0.03). With a median follow-up of 572 days, no statistically significant differences in overall survival (p = 0.67, HR 1.15 with 95% CI 0.60-2.22) or PFS (p = 0.57, HR 0.83 with 95% CI 0.43-1.59) were noted between the two groups, which were adjusted for age, gender, ethnicity, ECOG, PD-L1 status, grade of initial irAEs, and best objective response (OR) prior to initial irAEs. Conclusions: In real-world practice, clinicians tend to rechallenge patients with less severe irAEs. Our study showed that rechallenge was associated with a relative high risk of second grade≥2 irAEs. The risk was less if the initial irAEs were resolved. The second irAEs were not more severe than the first. Rechallenge can be performed under close monitoring, ideally, after the initial irAEs have completed resolved. The survival outcomes of ICI rechallenge and discontinuation were similar. ICI discontinuation is one feasible strategy after grade≥2 irAEs, especially severe irAEs.[Table: see text]

e21506 Background: Malignant melanoma (MM) of mucosal membranes (excluding anus and head and neck) is a rare but aggressive disease with poor outcome. There is little information available on the mechanism of development, risk factors and management of this tumor, mainly due to the low number of cases. Methods: We performed a literature review on MMM (between 1970-2020) with a focus on nonsurgical management and outcome. Results: We identified 9-papers discussing 1500-MM cases. Formerly, for the management of MMM, Dacarbazine, Interferon b, DAV-Feron, Carboplatin, Imatinib, and Paclitaxel were administered. More recently, novel immunotherapeutic and chemotherapeutic medications such as Immune Checkpoint Inhibitors (ICPI) and anti-VEGF agents have been administered in these patients. In 502 patients of metastatic MMM, adding ipilimumab to dacarbazine increased OS from 9.1-to-11.2 months with one year survival increasing from 36.3%-to-47.3 %. For nivolumab & ipilimumab combination therapy in 361 patients with MMM and CMM, MPSF in nivolumab monotherapy was 3-months and 6.2-months (for MMM and CMM, respectively); but in nivo-ipili combination, MPFS was 5.9-months and 11.7-months (for MMM and CMM, respectively). A benefit of bevacizumab addition to platinum-based chemotherapy in patients showing advanced disease on ICPI is unknown; however, combination-therapy may be reasonable if no access to ICPI or autoimmune diseases. Conclusions: MMM patients could benefit from combination of nivolumab to ipilimumab more than monotherapy with either medication alone.[Table: see text]

2525 Background: Immune checkpoint inhibitors (ICIs) can cause a variety of inflammatory autoimmune tissue damage, referred to as immune-related adverse events (irAEs). COVID-19 is associated with increased amounts of proinflammatory cytokines, which may synergistically affect the outcome of irAEs. Data are limited regarding the impact of COVID-19 on irAEs in ICI-treated cancer patients. Methods: We retrospectively analyzed adult patients with malignant solid tumors treated with ICIs at AdventHealth Orlando between August 2020 and August 2021. All COVID-19 infections were confirmed by PCR. Patients who had the most recent ICI treatment over one month before or after the positive COVID-19 test were excluded from the study. For COVID-19 positive group, only the irAEs that developed after COVID-19 infection were considered as events. Results: A total of 579 patients were included in our study, with 46 (7.9%) in COVID-19 positive group, and 533 (92.1%) in COVID-19 negative group. The baseline characteristics of patients in the two groups were similar in terms of age, ethnicity, ECOG, cancer histology, and type of ICI. With a median follow-up of 10 months (1-73 months), no differences in the time from ICI initiation to irAE onset, corticosteroid use, or additional immunosuppressant use were seen. A trend in higher incidence of all-grade diarrhea/colitis (8.7% vs. 3.0%, p=0.07) and grade 3 and 4 hepatitis (4.3% vs. 0.8%, p=0.08) was noted in the COVID-19 positive group, however the difference was not statistically significant. No significant difference in the incidence of pneumonitis (2.2% vs. 1.1%, p=0.44), nephritis (2.2% vs. 0.8%, p=0.34) or dermatitis (6.5% vs. 6.4%, p=1.00) were noted between COVID-19 positive and negative groups. We noticed a higher incidence of all-grade irAEs in the COVID-19 positive group (30.4% vs. 19.9%, p=0.18), but the difference was not statistically significant. The incidence of grade 3 and 4 irAEs was significantly higher in the COVID-19 positive group (10.9% vs. 3.2%, p=0.02). Nine COVID-19 related death occurred while no irAE-related death was noted in the entire cohort. Conclusions: Our study suggested that COVID-19 may pose a risk of severe irAEs in cancer patients receiving ICIs. Close monitoring and possible delaying ICI administration could be considered when cancer patients were infected with COVID-19. [Table: see text]