Wang, Jing

e21156 Background: Immunotherapy (IO) is one of the major treatments for patients with metastatic non-small cell lung cancer (mNSCLC). IO may be discontinued in patients for many reasons, the most common being progression of disease (POD). For those patients who discontinued IO for reasons other than POD, such as immune-related adverse event (irAE), there is limited data that compare progression-free survival (PFS) and overall survival (OS) when IO is continued vs. stopped. Methods: We conducted a retrospective study of all patients with mNSCLC (stage IV) treated with IO at our institution from 2011 to 2022. Patients who discontinued IO due to POD were excluded from the analysis. The clinical outcomes, including PFS, OS, and irAE were investigated among patients with no POD who stopped IO prior to 6 or 12 months (m) vs. those that continued IO > 6 or 12m. Results: The analysis at the 6m timepoint included 92 patients, 82.6% were white, 50% were male, 67.4% had adenocarcinoma, and 82.6% used tobacco. The most common site of metastasis was bone (28.3%), followed by CNS (20.7%). 51.2% of patients had received IO as the first line systemic therapy and 32.6% received it as their second. Pembrolizumab was the most used IO (84.78%). Among these patients, 25 discontinued IO before 6m, and 67 patients continued IO beyond 6m. irAE, of any grade, occurred in 44.0% vs 37.3% when comparing IO discontinued with IO continued group at 6m. Patients who continued treatment beyond 6m had a longer duration of PFS (22.8m vs 11.8m, p = 1.14E-04) with a significant increase in OS (34.5m vs 14.0m, p = 1.34E-07). The analysis at the 12m timepoint included 71 patients, 87.3% were white, 46.5% were male, 78.9% had adenocarcinoma, and 80.3% used tobacco. The most common site of metastasis was bone (29.9%), followed by CNS (22.5%). 62.0% of patients had received IO as the first line systemic therapy and 28.7% received it as their second. Pembrolizumab was the most used IO (87.3%). Among these patients, 30 discontinued IO before 12m, and 41 patients continued IO beyond 12m. irAE, of any grade, occurred in 36.7% vs 41.5% when comparing IO discontinued with IO continued group at 12m. Similarly, patients who continued treatment beyond 12m had a longer duration of PFS (28.4m vs 14.2m, p = 1.91E-06) with a significant increase in OS (39.9m vs 17.6m, p = 3.45E-09). Conclusions: We observed that patients with mNSCLC and no POD, who continued IO beyond 6m and 12m, experienced a significant increase in PFS and OS than those who discontinued IO, with more significant increases in those who continued IO past 12m. These findings need to be verified in a larger cohort.

Lung cancer remains the leading cause of cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC) is the most common type and is still incurable for most patients at the advanced stage. Targeted therapy is an effective treatment that has significantly improved survival in NSCLC patients with actionable mutations. However, therapy resistance occurs widely among patients leading to disease progression. In addition, many oncogenic driver mutations in NSCLC still lack targeted agents. New drugs are being developed and tested in clinical trials to overcome these challenges. This review aims to summarize emerging targeted therapy that have been conducted or initiated through first-in-human clinical trials in the past year.

Abstract Intravascular lymphoma (IVL) is a rare extranodal non‐Hodgkin lymphoma. We performed a retrospective analysis of 55 IVL patients who were treated at our institution 2003–2018. Median age at diagnosis was 68 years, and 64% were males. The most frequent presenting symptoms were skin rash 43% and weight loss 30%. MRI brain on IVL patients with CNS involvement (CNS‐IVL) showed multifocal involvement in 76% (13/17). 89% (17/19) of non‐CNS‐IVL patients with abnormal FDG‐PET had biopsy of an avid lesion resulting in definitive diagnosis. The top diagnostic biopsy site was the bone marrow (45%). 56% had multiorgan involvement. Based on CNS involvement, 36.5% (20/55) had CNS‐IVL and 63.5% (35/55) had non‐CNS‐IVL. CNS‐IVL group consists of clinically isolated CNS involvement (CNS‐only IVL) (22%;12/55) and mixed clinical CNS and peripheral site involvement (M‐IVL) (14.5%; 8/55). Non‐CNS‐IVL group consists of clinically isolated skin involvement (skin‐only IVL) (9%; 5/55) and peripheral IVL with or without skin involvement (P‐IVL); (54.5%; 30/55). Skin involvement was predominantly in the lower extremities. Pathologically, 89% (48/54) were B‐cell IVL. Rituximab + high‐dose methotrexate‐based regimen were used in 75% (12/16) of CNS‐IVL patients and RCHOP in 60% (17/28) of non‐CNS‐IVL patients. Estimated 5‐year progression free survival (PFS) and overall survival (OS) for the entire cohort were 38.6% and 52%, respectively. Skin‐only IVL was associated with excellent survival. Platelet count <150x10 9 /L, age > 60Y, and treatment without Rituximab were poor prognostic factors. Further research is necessary to identify novel therapies.