Retrospective analysis of NUT carcinoma: The Northwestern experience

e18096 Background: NUT carcinoma (NC) is a rare, highly aggressive carcinoma that originates from a wide variety of organs, typically presenting as poorly differentiated squamous cell carcinoma. Cases typically are aggressive, with a median overall survival (OS) of only 6.5 months. Given only 40-50 cases are diagnosed in the United States annually, NC is an orphan disease with no standard treatment options and the outlook is generally poor. A previously published case of thyroid NUT carcinoma demonstrated a prolonged response to pembrolizumab for > 3 years. Methods: Patients (pts) harboring NUTM1 rearrangements were retrospectively identified at our institution. We reviewed characteristics related to tumor immune microenvironments by tumor immunohistochemistry and next generation sequencing as well as clinical outcomes. Results: 10 NMC pts were identified (5 female, 5 male): lung (6), thyroid (2), primary mediastinal (1), maxillary sinus (1). The median age at diagnosis was 49 years (range of 27-75). The thyroid cases were diagnosed at ages 51 and 75. 8/10 had metastatic or unresectable disease at diagnosis, 3 of which with central nervous system metastases. In 8 evaluable patients, NUTM1 rearrangements included BRD2 (1), BRD3 (1), BRD4 (2), NSD3 (3), SCL12A6 (1). Median OS was 10.8 months (range 1.1-75.8m); 3/10 patients were deceased. 3 patients received IO (2 ipilimumab/nivolumab, 1 pembrolizumab) after either surgery, RT, or chemotherapy combined with RT. Patients who received IO had a median survival of 18 months (range 10.9-76.0 months) compared with 8.5 months in the 8 patients not receiving IO (p = 0.07). All patients with tissue available in this cohort all had PD-L1 staining < 5%, were microsatellite stable (MSS) and had a low median tumor mutation burden (TMB) of 3.1 mut/Mb. Conclusions: In our series, NC originating from the thyroid gland accounted for more cases than expected, thyroid NC patients were older than NC cases arising in other locations and with the more typical squamous histology. Despite relatively low PD-L1 staining, TMB, and MS status, our data suggests NMC tumors may be amenable to treatment with immune checkpoint inhibitors, warranting further investigation.