Pharmaceuticals, Inivata, MD Serono, and Novartis; fees for speakers bureau from AstraZeneca, Merck Sharp & Dohme, and Roche; and nonfinancial support from Guardant Health through a research collaboration. Dr. Russo reports receiving personal fees for attending advisory board meetings from AstraZeneca, Merck Sharp & Dohme, and Novartis. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serologic assays and NDV-based SARS-CoV-2 vaccines which list Dr. Krammer as coinventor. Mount Sinai has spun out a company, Kantaro, to market serologic tests for SARS-CoV-2. Dr. Krammer has consulted for Merck and Pfizer (before 2020

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Clinicians have continued to report on the clinical behavior and characteristics of patients with coronavirus disease 2019 (COVID-19) as our knowledge of the virus continues to mature. Herein, we report the case of a 39-year-old male with multiple comorbidities who became critically ill with COVID-19 infection, requiring mechanical ventilation and vasopressors, and then developed agranulocytosis following clinical improvement and resolution of symptoms of COVID infection. The period of agranulocytosis coincided with the development of thrombocytosis, and following resolution of agranulocytosis, the platelet count also normalized, suggesting a possible related mechanism. Interestingly, the patient was treated with TBO-filgrastim 480 mcg daily with a rapid reconstitution of neutrophils. While the mechanism of agranulocytosis remains unknown, we report, to our knowledge, the first known case of agranulocytosis following COVID-19 infection and its successful treatment with granulocyte colony-stimulating factor.

Small cell lung cancer (SCLC) is a highly proliferative lung cancer that is not amenable to surgery in most cases due to the high metastatic potential. Precision medicine has not yet improved patients’ survival due to the lack of actionable mutations. Intra- and intertumoral heterogeneity allow the neoplasms to adapt to various microenvironments and treatments. Further studying this heterogeneous cancer might yield the discovery of actionable mutations. First-line SCLC treatment has added immunotherapy to its armamentarium. There has been renewed interest in SCLC, and numerous clinical trials are underway with novel therapeutic approaches. Understanding the molecular and genetic landscape of this heterogeneous and lethal disease will pave the way for novel drug development.

Inflammatory myofibroblastic tumors (IMTs) are intermediate-grade mesenchymal neoplasms commonly characterized by chromosomal rearrangements causing constitutive activation of anaplastic lymphoma kinase (ALK) and/or ALK mutations causing reduced sensitivity to ALK tyrosine kinase inhibitors (TKI). We present a patient with an IMT who initially responded to first-line alectinib, but who later suffered disease relapse and presently survives with moderate residual disease after receiving second-line lorlatinib. Biopsy specimens were analyzed using next generation sequencing (DNA-seq and RNA-seq) and reverse phase protein microarray (RPPA) as part of an institutional Molecular Tumor Board (MTB) study. An EML4-ALK rearrangement and EGFR activation (pEGFRY1068) were present in both the primary and recurrent tumors, while a secondary ALK I1171N mutation was exclusive to the latter. EGFR signaling in the background of a secondary ALK mutation is correlated with reduced ALK TKI sensitivity in vitro, implicating an important mechanism of drug resistance development in this patient. The RPPA results also critically demonstrate that ALK signaling (ALKY1604) was not activated in the recurrent tumor, thereby indicating that standard-of-care use of third- or fourth-line ALK TKI would not likely be efficacious or durable. These results underscore the importance of real-time clinical integration of functional protein drug target activation data with NGS in the MTB setting for improving selection of patient-tailored therapy.

Introduction: Skeletal related events (SRE) in multiple myeloma (MM) patients are associated with significant morbidity and mortality. Studies assessing the anti myeloma effect of statins in conjunction with chemotherapy have shown conflicting results with regards to overall survival or disease response. To our knowledge there have been no studies evaluating the effect of statins on SRE. Here we sought to assess the relationship between statin use and the presence of SRE. Methods: We retrospectively reviewed 101 patients seen at our institution between the years 2007-2012 who had a diagnosis of MM separating them in 2 groups, patients on statin therapy (n=50) and those without statin therapy (n=51). Statin use was considered if present prior to the occurrence of a SRE. SRE were defined as pathologic fractures, necessity for orthopedic intervention, radiation therapy or spinal cord compression. MM stage as per the International Staging System (ISS), as well as history of osteoporosis, malignancy, hypothyroidism, Paget's disease of the bone, alcohol abuse, smoking status, calcium-vitamin D, and bisphosphonate use were also recorded. Results: In our cohorts the prevalence of SRE was significantly lower in patients on statin medication when compared to statin naive patients, (36% vs. 58.8% respectively, p = 0.029, Fisher's exact test, Figure 1). No significant differences were noted between statin treated group and statin naive group in the following variable subgroups (Fisher's exact test): the history of smoking or alcohol abuse, the documented diagnosis of osteoporosis, coexistent malignancy, hypothyroidism, or Paget's disease of the bone, and the use of other medications including bisphosphonates or calcium - vitamin D supplementation. There were no significant differences in distribution of cancer staging (according to ISS) when we compared between statin use status (chi-square test for trend). Conclusion: The use of statins was associated with a decrease in the prevalence of SRE in patients with MM. This was found independent of disease stage, history of osteoporosis or second malignancy, and bisphosphonate use. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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