Ravindran, Aishwarya

Introduction Due to the higher metabolic demand, malignant cells have an increased dependency on the nucleocytoplasmic trafficking of proteins, as compared to normal cells. Chromosome region maintenance protein 1 (CRM1), encoded by the XPO1 gene, is the main protein receptor which facilitates export of molecules, including tumor suppressor proteins, from the nucleus to the cytoplasm thereby making them inactive. Expression of CRM1 in tumor tissue has been shown to be an independent prognostic marker in several solid tumors and in acute myeloid leukemia; high CRM1 expression by immunohistochemistry (IHC) was associated with more aggressive disease and shorter survival. Importantly, selinexor, a first in class small molecule inhibitor of CRM1, was recently approved for the treatment of relapsed diffuse large B-cell lymphoma (DLBCL). The expression of CRM1 on tumor cells and the assessment of its prognostic impact have not been studied in patients (pts) with DLBCL or primary mediastinal B-cell lymphomas (PMBCL). Methods Paraffin embedded tumor tissue from pts with DLBCL or PMBCL treated with immunochemotherapy was assessed for CRM1 expression through IHC on tissue microarray (TMA). CRM1 anti-rabbit monoclonal antibody (Cell Signaling, catalog-no: 46249) was used at 1:100 dilution. Tumor cell grading was based on CRM1 staining in tumor cells compared to background non-malignant lymphocytes and non-malignant lymphocytes in spleen and tonsillar tissue controls. Renal cell carcinoma (RCC) was used as a positive control [known high levels of CRM1 staining (Inoue et al, J Urol, 2012)]. Two expert hematopathologists (RLK & AJW) independently scored CRM1 nuclear staining and assigned a grade of 0-3; 0 (no definitive nuclear staining, equal to background lymphocytes), 1 (dim nuclear staining), 2 (consistent nuclear staining, nuclear detail still visible behind the stain) and 3 (strong nuclear staining obscuring most nuclear detail, staining equivalent to RCC control). The average CRM1 score per case across all available cores on the TMA was calculated. Low CRM1 expression for a case was arbitrarily defined as a score of 0-2.0; high CRM1 expression was score 2.1-3.0. Scoring reliability between reviewers and between cores was assessed using intra-class correlation coefficient; score 0.75-0.90 was considered as a good scoring reliability. Event-free survival (EFS) was defined as time from diagnosis to progression, relapse, retreatment, or death. The association of CRM1 expression and risk of failing to achieve EFS at 24 months after diagnosis (EFS24) was estimated using odds ratios (OR) and 95% confidence intervals (CI) from logistic regression models, while the association of CRM1 expression with continuous EFS and overall survival (OS) was estimated using Kaplan-Meier curves and hazard ratios (HR) and 95% CI from Cox regression models. Results Tumor tissue from 282 pts was studied for CRM1 staining, including 275 pts with DLBCL and 7 pts with PMBCL. Median age of the study population was 61 years (range: 18-93) and 59% were male. The median follow-up for the entire cohort was 88.6 months. The first-line treatment regimens and baseline patient characteristics at diagnosis are outlined in Figure 1A. Of the 282 pts, 200 (71%) had high level of CRM1 expression and 82 (29%) had low CRM1 expression [only 4 (1.4%) had no or 0 staining]. Intra-class correlation coefficient to measure scoring reliability was 0.8. There was no difference in International Prognostic Index (IPI), ECOG performance score, lactate dehydrogenase or age at diagnosis among the groups with high CRM1 expression compared to low CRM1 expression (Figure 1A). The EFS24 failure was 29% for pts with low CRM1 expression while 26% in pts who had high CRM1 expression, OR=1.16, 95% CI 0.63-2.07; p=0.63. Null associations were also observed for EFS (HR=1.21, 95% CI 0.80-1.83; p=0.38) and OS (HR=1.02, 95% CI 0.61-1.69; p=0.95), (Figure 1B, C). Results were similar when adjusted for gender and IPI. Conclusion CRM1 expression by IHC on paraffin embedded tumor tissue is feasible in DLBCL and PMBCL. These data demonstrate that the CRM1 protein, the target for selinexor, is indeed expressed in the vast majority of these tumors; only 1.4% had no staining. However, CRM1 expression by IHC is not a prognostic marker for EFS24, EFS or OS. Whether CRM1 staining predicts selinexor response has not been studied but should be included in any new studies using CRM1 inhibitors. Disclosures Maurer: Nanostring: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Celgene / BMS: Research Funding. Cerhan:BMS/Celgene: Research Funding; NanoString: Research Funding. Witzig:Acerta: Research Funding; Immune Design: Research Funding; Incyte: Consultancy; MorphSys: Consultancy; Celgene: Consultancy, Research Funding; Spectrum: Consultancy; Karyopharm Therapeutics: Research Funding; AbbVie: Consultancy.

Chromosome region maintenance protein1 (CRM1) mediates protein export from the nucleus and is a new target for anti-cancer therapeutics. Broader application of KPT-330 (selinexor), a first in class CRM1 inhibitor recently approved for multiple myeloma and diffuse large B-cell lymphoma (DLBCL), has been limited by substantial adverse effects (AEs). To address this clinical problem, we focused on identifying novel strategies to boost the potency, reduce toxicity, and broaden the applicability of CRM1 inhibitors to a wider range of malignancies. We discovered that salicylates could markedly enhance the anti-tumor activity of CRM1 inhibitors by extending the mechanisms of action beyond CRM1 inhibition. KPT-330 was chosen as the prototypical CRM1 inhibitor given its current FDA approval status and characterized pharmacokinetics; and choline salicylate (CS) was chosen as the prototypical salicylate given its favorable pharmacokinetics and reduced antiplatelet, renal, neurological and gastrointestinal AEs in humans compared to other salicylates. By using cell lines belonging to different hematologic malignancies and solid tumors, we demonstrated ex vivo that the combination of KPT-330 and CS (K+CS) could induce unique and significant antitumor effect at much lower dose of KPT-330 (at 25% of the dose used in the clinic), thereby potentially mitigating prohibitive clinical AEs (Figure 1a-d, and e-g). This significant synergetic antitumor effect observed with K+CS ex vivo was also validated in vivo by using an NSG mouse model of mantle cell lymphoma (Figure 1h). Moreover, the K+CS combination did not show this potent toxic effect on non-malignant cells in vivo and was safe without inducing toxicity to normal organs in NSG mice. Mechanistically, protein profiling through mass spectroscopy revealed that K+CS uniquely affects the cellular pathways of DNA damage repair, DNA synthesis and cell cycle progression. Studies involving immunoblotting, cell cycle analysis, immunofluorescence microscopy assessing nucleocytoplasmic molecular export and DNA damage, reporter assay to assess homologous recombination repair proficiency and immunohistochemistry showed that, compared to KPT-330 treatment alone, K+CS decreased the expression of CRM1, Rad51 and thymidylate synthase proteins in vitro and in vivo, leading to more efficient inhibition of CRM1-mediated nuclear export, impairment of DNA-damage repair, reduced pyrimidine synthesis, and importantly a unique cell cycle arrest in S-phase, thus leading to cell apoptosis. These effects on cellular proteins and pathways were unique to K+CS treatment and were not observed with KPT-330 or CS single agent treatment. Pathway analyses through RNA sequencing also paralleled the findings of proteomic studies thus further validating the unique effect of K+CS treatment on the aforementioned cellular pathways. Importantly, K+CS treatment exerted unique and significant antitumor effect ex vivo on primary malignant cells obtained from patient's with high-risk hematologic malignancies such as double hit DLBCL, BTK and BCL2 inhibitor resistant mantle cell lymphoma, TP53 deleted/mutated chronic lymphocytic leukemia and high-risk multiple myeloma thus signifying its broader applicability as a treatment option for these aggressive hematologic malignancies where there is a dire need to find new treatment strategies (Figure 1i). In summary, we describe a unique all-oral drug combination with a novel constellation of mechanisms of action on cellular pathways that are exploited by cancer cells. K+CS represents a new class of therapy for multiple cancer types and will stimulate future investigations to exploit DNA-damage repair and nucleocytoplasmic transport for therapy of blood cancers. Disclosures Witzig: Karyopharm Therapeutics: Research Funding; Acerta: Research Funding; Incyte: Consultancy; AbbVie: Consultancy; Celgene: Consultancy, Research Funding; MorphSys: Consultancy; Immune Design: Research Funding; Spectrum: Consultancy.

Abstract Chromosome region maintenance protein 1 (CRM1) mediates protein export from the nucleus and is a new target for anticancer therapeutics. Broader application of KPT-330 (selinexor), a first-in-class CRM1 inhibitor recently approved for relapsed multiple myeloma and diffuse large B-cell lymphoma, have been limited by substantial toxicity. We discovered that salicylates markedly enhance the antitumor activity of CRM1 inhibitors by extending the mechanisms of action beyond CRM1 inhibition. Using salicylates in combination enables targeting of a range of blood cancers with a much lower dose of selinexor, thereby potentially mitigating prohibitive clinical adverse effects. Choline salicylate (CS) with low-dose KPT-330 (K+CS) had potent, broad activity across high-risk hematological malignancies and solid-organ cancers ex vivo and in vivo. The K+CS combination was not toxic to nonmalignant cells as compared with malignant cells and was safe without inducing toxicity to normal organs in mice. Mechanistically, compared with KPT-330 alone, K+CS suppresses the expression of CRM1, Rad51, and thymidylate synthase proteins, leading to more efficient inhibition of CRM1-mediated nuclear export, impairment of DNA-damage repair, reduced pyrimidine synthesis, cell-cycle arrest in S-phase, and cell apoptosis. Moreover, the addition of poly (ADP-ribose) polymerase inhibitors further potentiates the K+CS antitumor effect. K+CS represents a new class of therapy for multiple types of blood cancers and will stimulate future investigations to exploit DNA-damage repair and nucleocytoplasmic transport for cancer therapy in general.

Abstract Introduction/Objective Non-mass enhancement (NME) in breast tissue is an area of enhancement on MRI that appears distinct from background breast parenchyma, but lacks definitive features of a mass. NME is characterized by its internal enhancement pattern and distribution, and can represent benign, high risk, or malignant pathology. Given this considerable overlap, a core biopsy is often necessary for diagnosis and management. We aimed to elucidate the most frequent histologic findings found on breast biopsies for MRI NME. Methods Using our institutional database we identified 70 female patients with high risk status for breast cancer with MRI screen detected NME (BIRADS-4-suspicious for malignancy) that underwent subsequent biopsy procedure during the period of 01/2016-12/2017. Primary pathologic diagnoses were subcategorized as follows: malignant, atypical, benign mass-like lesions, fibrocystic changes (proliferative, nonproliferative), or “other” primary diagnoses. Results The median age of patients was 48 years (range: 22-76 years). Of the 70 patients, 66 underwent MRI-guided core biopsy, 3 underwent ultrasound-guided core biopsy and 1 underwent excisional biopsy. The primary diagnosis was analyzed. Of these 70 cases, 8 (11.4%) were malignant (7 with ductal carcinoma in situ and 1 with invasive ductal carcinoma), 1 (1.4%) had atypical lobular hyperplasia, and the remaining 61 (87.1%) showed benign findings (36 with fibrocystic changes (FCC), 22 benign mass-like lesions, 3 with other non-specific findings). The FCC were subcategorized as proliferative (usual ductal hyperplasia, columnar cell change, incidental radial scar, incidental intraductal papilloma, sclerosing adenosis, focal pseudoangiomatous stromal hyperplasia (PASH)) or nonprolifeative (stromal fibrosis, duct ectasia, apocrine metaplasia). Majority (61.1%) of FCC were both proliferative and nonproliferative, 22.2% proliferative only and 16.7% nonproliferative only. Benign mass-like lesions included PASH (45.4%), fibroadenomatoid nodule (22.7%), fat necrosis (18.2 %) and remaining had the diagnosis of clustered apocrine cysts, papillomatosis, and radial sclerosing lesion. Conclusion Less than a third of cases showed malignant findings and more than two-third of cases showed benign findings with a high rate of detection of proliferative lesions and PASH.

Abstract Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm. To date, there is a lack of U.S. Food and Drug Administration–approved treatments in adult LCH to establish optimal first-line therapy. We conducted a retrospective, single-center case series evaluating the use of BRAF inhibitors in adult patients with BRAFV600E- LCH proven by biopsy. Our case series is the first to report the use of BRAF inhibitors as first-line therapy in adults with LCH. We also report the efficacy with single-agent dabrafenib in adult LCH. All but one of our patients had favorable response to targeted therapy.

Abstract BACKGROUND: Thrombocytopenia is a common hematologic condition associated with multiple etiologies ranging from benign to malignant to potentially life-threatening disorders. Given the heterogeneity of clinical presentations, available clinical information, and pertinent clinical history, there are inter-physician variations in the approach to the workup of thrombocytopenia in the hematology clinic. While a limited test repertoire may be adequate for many cases, more extensive testing may be warranted in others. We were interested in analyzing the various tests performed and testing approaches in the initial workup of thrombocytopenia. METHODS: We reviewed the records of 69 patients who were referred to our center between 2010 and 2015 for an initial workup of thrombocytopenia. We collected epidemiologic data, laboratory testing results, and pathologic findings. Pathologic results were classified as "normal" or "abnormal" and further subcategorized on the basis of review by two clinicians. Quantitative data were analyzed using JMP Pro 10.0.2 software. RESULTS: At the time of thrombocytopenia diagnosis, the median age was 59 years (range: 17-90) and majority were males (65%). The median platelet count was 91,000/µL (range: 3,000-146,000). Isolated thrombocytopenia was present in 51 cases (74%). Forty-four patients (64%) had a peripheral blood smear review and 4 (9%) contained abnormalities including hypogranular neutrophils, rouleaux formation, and target cells. Autoimmune workup included anti-platelet antibody (APA) in 34 (49%), anti-nuclear antibody (ANA) in 21 (30%), lupus anticoagulant (LA) in 4 (6%) and rheumatoid factor (RF) in 13 (19%) of cases. Autoimmune testing was positive for APA in 2 (5.9%), ANA in 4 (19%), LA in 0 (0%), and RF in 1 (8%) of patients who underwent testing, respectively. Common infectious workups included human immunodeficiency virus in 23 (33%), hepatitis A virus in 2 (3%), hepatitis B virus in 11 (16%), hepatitis C virus in 22 (32%), Epstein-Barr virus in 5 (EBV, 7%), cytomegalovirus in 7 (10%) and Helicobacter pylori in 5 (7%) of patients, and were negative in all cases except for one patient with evidence of active EBV infection. Sixteen patients (23%) underwent bone marrow biopsy, and 2 (12.5%) were diagnosed with hematologic malignancies including myelodysplastic syndrome and hairy cell leukemia. Based on results of these tests, 28 (41%) patients were diagnosed with primary immune thrombocytopenia, 19 (27%) with thrombocytopenia secondary to another medical condition, and 22 (32%) with thrombocytopenia of undefined etiology. CONCLUSION: Thrombocytopenia is a common laboratory finding, and workup involves significant inter-clinician variation, often involving multiple laboratory tests and in some cases invasive tests such as bone marrow biopsy. We found that autoimmune causes of thrombocytopenia were moderately common and infectious and malignant causes were rare. Our findings were based on a small cohort of patients but are likely to be representative of the clinical practice in a large tertiary care center. Large scale studies may be warranted to devise a protocol for a thorough yet cost-effective and stepwise initial workup of thrombocytopenia and to minimize unwarranted inter-clinician variation in such investigations. Disclosures No relevant conflicts of interest to declare.

Introduction: The compulsive craving and consumption of non-food substances, known as pica, is a well-documented symptom associated with iron deficiency anemia (IDA). Olfactory cravings associated with IDA are a recently described phenomenon known as desiderosmia. In our practice we observed a subset of patients with IDA who report specific tactile cravings associated with mastication. Methods: This study included patients from the Mayo Clinic (Rochester, MN) and Ankara Training and Research Hospital (Ankara, Turkey) Hematology practices who self-reported tactile mastication cravings during initial evaluation for IDA between 1/1/18 and 6/30/19. Information including sociodemographics, substance craved, values of hemoglobin (Hgb), mean corpuscular volume (MCV), and ferritin before and after iron replacement therapy, and symptom resolution after treatment were recorded. Results: We observed 12 patients with IDA who self-reported chew cravings during initial evaluation. All patients were female and the median age was 41.5 years (33-59). Of these 12 patients, median baseline Hgb, MCV, and ferritin were 9.4 g/dL (6.6-12.9), 73.7 fL (59.1-95.1), and 6 µg/L (2-21), respectively. Tactile cravings included chewing gum (3), mastic gum (2), ginseng (1), dry oats (1), crackers (1), pickles (1), chips (1), sawdust (1), and knitting rope (1). Many patients reported the frequency and satisfaction of these cravings resulted in jaw pain as well as the persistence of cravings despite this discomfort. Only 16.7% (2/12) reported concurrent ice pica. In total, 9 patients proceeded with observed treatment of their IDA with clinical follow-up and laboratory confirmation of iron repletion. Oral (ferrous glyconate or ferrous fumarate) and intravenous (ferric carboxymaltose, iron sucrose, or low molecular weight iron dextran) iron replacement were used in 33.3% (3/9) and 66.7% (6/9) patients, respectively. Post-treatment median laboratory values include: Hgb 12.7 g/dL (10.8-14.7), MCV 80.1 fL (76.1-91.7), and ferritin 98 µg/L (24-398). Overall, 88.9% (8/9) reported resolution of chew cravings after iron repletion. The lone patient with persistent symptoms had a baseline ferritin of 10 µg/L, improved to 398 µg/L after replacement, and settled back at 42 µg/L three months later. Discussion: Our patient experience provides suggestive evidence that oral tactile craving symptoms, distinct from ice pica, exists in a subset of patients suffering from IDA. For this, we propose the term "desideromastica" derived from the Latin words "desiderare" for desire and "mastica" for chew. "Desidero" can also be indicative of a reduction in iron, which relates to iron deficiency. Our hope in naming this relatively unexplored symptom associated with IDA will encourage additional clinicians to share their experience and guide future investigation. Disclosures No relevant conflicts of interest to declare.

Abstract Introduction Myelodysplastic syndromes (MDS) are heterogeneous myeloid disorders characterized by dysplasia in one or more hematopoietic cell lines, peripheral cytopenia(s), and distinct cytogenetic abnormalities. The presence of certain cytogenetic abnormalities [e.g. 7/del(7q), -5/del(5q), 13/del(13q), i(17p)], in the setting of unexplained persistent cytopenia, has been considered presumptive evidence of MDS, despite definitive morphologic features of MDS. Conversely, chromosomal abnormalities such as isolated 20q- are not considered definitive evidence for MDS, in the absence of dysplasia. Based on our previous findings, patients with isolated 20q- without morphologic features of a myeloid neoplasm have varied clinical outcomes (Jawad MD et al. Am J Hematol.2016). In this study, we investigate the frequency of recurrent somatic gene mutations in these patients, and their relationship to progression to a myeloid neoplasm. Methods We retrospectively reviewed the bone marrow pathology reports of patients evaluated at our institution from 01/2005 to 09/2015 who had isolated 20q- in at least 2 of 20 metaphases. Patients with isolated 20q- and without myeloid neoplasms were included in the study, along with medical record review. A 35-gene next generation sequencing (NGS) panel (OncoHeme) targeting myeloid neoplasms was performed on available archived bone marrow aspirate pellets. Statistical analyses were performed using JMP Pro software version 13. Parametric (t-test) or nonparametric tests such as the Fisher-exact test, chi-square test, or Wilcoxon rank-sum test, were utilized as appropriate for test variables. Statistical significance was based on a 2-sided significance level of .05. Kaplan-Meier analysis was used for analyzing time to progression to myeloid neoplasms and progression-free survival (i.e. time to progression to myeloid neoplasms or death from any cause). Results Fifty-six (42 males, 14 females) patients with isolated 20q- were identified. The average percentage of 20q- was 38.5 % (±29.3). The median age was 68 years (range: 44-90) and the median hemoglobin (Hb), absolute neutrophil count (ANC) and platelet count (Plt) were 11.7 g/dL (range: 8.3-15.1), 2.7 x 10(9)/L (range: 0.6-9.4) and 138 x 10(9)/L (range: 16-392), respectively. The indications for bone marrow biopsies ranged from cytopenia (21), multiple myeloma (20), non-Hodgkin lymphoma (10), amyloidosis (2), CLL (2) and transplant donor evaluation (1). Twenty-three patients harbored pathogenic mutations (15 had one mutation, 1 had two mutations and 7 had three mutations). The identified pathogenic mutations included ASXL1 (8), TET2 (8), SRSF2(3),PHF6 (2), SF3B1 (2), CBL (2), U2AF1 (2), IDH1 (1), IDH2 (1), BCOR (1), JAK2 (1), PTPN11(1), TP53 (1) and RUNX1 (1). Nine patients (16.1%) progressed to myeloid neoplasms (5 MDS, 2 acute myeloid leukemia, 2 chronic myeloid neoplasm-not otherwise specified) at a median follow-up of 36.7 months (range: 1.9-57.4). Of these 9 patients, 5 had one mutation (BCOR, TET2, DNM3TA, CBL, IDH2), 1 had two mutations (SF3B1/CBL) and 3 had three mutations (ASXL1/IDH1/SRSF2,DNM3TA/PTPN11/TET2, PHF6/TET2/TET2). In contrast, only 29.8% of non-progressed cases showed at least 1 mutation. Kaplan-Meier analysis demonstrated the presence of genetic mutations in patients with isolated 20q- carried significantly higher chance of progression to myeloid neoplasms (p<.05, Figure 1A and 1B). However, the number of genetic mutations was not predictive of progression in our relatively small study cohort (p=.66). There was no significant difference between those who did and did not progress with respect to age, gender, Hb, ANC, Plt, 20q- or mutational allele burden. Conclusions Most of the patients with isolated 20q- and without morphologic features of a myeloid neoplasm did not harbor myeloid neoplasm associated gene mutations and further did not develop a myeloid neoplasm during the course of our study. Among patients with pathogenic mutations, nearly one-third showed progression to a myeloid neoplasm. Of the clinical and laboratory variables, the presence of genetic mutation is a significant risk factor for progression to a myeloid neoplasm. This study revealed the underlying molecular heterogeneity of isolated 20q- in the absence of morphologic features of a myeloid neoplasm, and underscored the prognostication value of genetic mutation analysis in these cases. Disclosures No relevant conflicts of interest to declare.

Abstract Introduction: MGUS is generally an incidental finding in the diagnostic work-up for clinical signs and symptoms suggestive of lymphoplasmacytic malignancies (multiple myeloma, light chain amyloidosis, and Waldenström macroglobulinemia), which are relatively rare (<35,000 annual new cases in the US). While much is known about the natural history of MGUS, information regarding the pre- and post-diagnostic part of MGUS patient care is lacking. Our study objectives were to determine the following: 1) indications for monoclonal protein testing; 2) subsequent diagnoses found for those indications; 3) specialty of ordering clinicians; 4) follow-up patterns after MGUS diagnosis. Methods: We identified MGUS patients residing in southeastern Minnesota who were diagnosed from 2011-2014 and followed at the Mayo Clinic. Medical records were reviewed to confirm the diagnosis and obtain relevant clinical data. Laboratory tests and visits were identified using Current Procedural Terminology-4th edition (CPT-4) codes from billing data. We defined a follow-up visit as: 1) any face-to-face encounter linked to MGUS diagnosis 30 days after the date of MGUS diagnosis regardless of whether ancillary test was performed or not; and 2) MGUS-specific tests or laboratory tests linked to an MGUS diagnosis claim performed without a face-to-face encounter. Based on the Mayo Clinic MGUS risk stratification model, we classified our cohort into either low-risk or non-low risk. Criteria for low-risk used were: serum monoclonal protein <1.5 g/dL, IgG subtype, and normal serum free light chain ratio. Follow-up patterns were analyzed according to year of diagnosis, demographics, and the specialty of clinicians performing the follow-up. Results: 330 MGUS patients were included in the study. The median age at diagnosis was 73 years (range, 21-98) and most were males (59.7%). The common indications for monoclonal protein studies were neuropathy (19.6%), kidney disease (13.6%), anemia (12.7%), bone symptoms/signs (12.7%), cutaneous disorders (5.8%), congestive heart failure (4.8%), and hypercalcemia (2.7%). The most common subsequent diagnoses for these indications were neuropathy not otherwise specified (NOS;100%), chronic kidney disease NOS (35.5%), anemia of chronic kidney disease (19%), osteopenia/osteoporosis (45.2%), congestive heart failure NOS (57.1%), and dermatitis NOS (100%), respectively. The practice specialties that most commonly diagnosed MGUS were internal medicine (31.3%), neurology (13.7%), nephrology (10.3%), family medicine (6.1%), and hematology (5.8%). Low risk MGUS comprised 44.8% of the cohort. After a median follow-up of 53.5 months (range, 13.0-77.4; IQR, 40.8-77.4), the total number of follow-up visits was 937. Majority (85.5%) of the visits were a combination of office visit with laboratory testing, while the rest were either office visit (11.2%) or laboratory tests (3.3%) only. The distribution of patients by mean interval between visits was: every <6 months (7.9%); every 6-12 months (19.4%); every 13-24 months (15.2%), and every >24 months or no follow-up at all (57.6%). The follow-up patterns did not change significantly (Kruskal Wallis; P=0.6759) over time (Figure 1) and were similar when age groups were compared (Figure 2; P=0.1328). However, males were followed more frequently than females (P=0.0365). Among patients 80 years and older, 32.1% continued to be followed at least once every 2 years (Figure 2). Hematologists were more likely than non-hematologists to follow MGUS patients regardless of the risk category (Figures 3-4). Among low risk patients, 31.1%, 22.2%, 20.7%, and 19.1% had at least one follow-up during years 2, 3, 4, and 5, after MGUS diagnosis (Figure 3). Conclusions: Approximately 1/3 of MGUS diagnoses were made during the evaluation of signs and symptoms not related to lymphoplasmacytic malignancies. The subsequent diagnoses found were a wide variety of common diseases. Most MGUS diagnoses were made by general internists, neurologists, and nephrologists. Follow-up practices varied between hematologists and non-hematologists. Nearly 1/3 of the oldest old patients continued to have follow-up, despite limited life expectancy. Disclosures No relevant conflicts of interest to declare.