The Impact of the Sars-Cov-2 Pandemic (COVID-19) on the Incidence of Newly Diagnosed Multiple Myeloma Patients Using a Federated Network of Real-World Evidence in US and Germany

Objectives: COVID-19 had an impact on health care, including diagnostics. Early diagnosis of MM is a critical factor for prognosis. We examined the impact of COVID-19 on incidence of NDMM patients and on characteristics in NDMM patients in US and in Germany. Method(s): 44,164 NDMM patients were identified in TriNetX federated network across 55 healthcare organizations in US between January 2018 and December 2021. A bivariate analysis examined changes in patient characteristics in two cohorts before (Cohort 1;n=25513) and after (Cohort 2;n=18.651) the start of the COVID-19 pandemic in March 2020. 4172 NDMM patients were identified in the German database in a sample of across >100 healthcare organizations in the same time period. Similarly, bivariate analysis examined changes in patient characteristics before (Cohort 1;n=2252) and after (Cohort 2;n=1920) the start of pandemic. Result(s): Analysis of US data showed a significant decrease in incidence of NDMM. Bivariate analysis revealed that NDMM patients in Cohort 2 have a significantly higher risk profile compared with patients in Cohort 1, higher incidence of renal failure (13.5% v. 15.43%), heart failure (10.3% v 11.26%), bone lesions (12.6% v. 13.05%) and anemia (26.8% v. 29.75%). The German data indicated an increased risk profile in Cohort 2, with higher reporting of renal impairment (12.3% v. 15.5%) and cardiac impairment (8.3% v. 10.9%). The higher risk profile was reflected in a significant increase of all SLiM-CRAB criteria, notably hypercalcemia (24.1 % v. 36.9%), bone marrow plasma cell infiltration (28.1% v. 36.8%) and free light chain involvement (27.3% v. 41.3%). Conclusion(s): The results provide real-world evidence of a change in risk profile for patients with NDMM during COVID-19. This higher risk profile is observed in both the US and Germany, and may negatively impact outcomes such as progression-free and five-year overall survival.Copyright © 2023

PSMA PET/CT Detected Prostate Cancer Metastasis in a Patient with Negative mpMRI and Prostate Gland Biopsy

Aim/Introduction: This is a case of [68 Ga]Ga-Prostate-specific membrane antigen(PSMA)-11 PET/CT in a 73-years old patient with significantly high iPSA level despite both multiparametric magnetic resonance imaging (mpMRI) and 12-core saturation biopsy negative for prostate cancer (Pca). Material(s) and Method(s): In November 2021 the patient underwent a routinary abdomen ultrasound with the detection of several pelvic and retro-peritoneal adenomegalies, confirmed by diagnostic CT. Initially the suspect of Pca origin was raised, due to high PSA levels (55 ng/dl versus 2.1ng/dl the previous year). A 12-samples saturation biopsy was then performed, with inconclusive result. Nevertheless, due to further increase in PSA level up to 77ng/dl in December (PSA doubling time approximately 4 months), a mpMRI was performed in January showing absence of clinically significant PCa (PIRADS 2) and persistence of enlarged pelvic lymph nodes. The patient was subsequently referred for a [68Ga]Ga-PSMA-PET/CT, which was performed and reported following standard EANM guidelines. A delayed 90 min scan on the pelvis was also acquired. Result(s): In accordance with previous mpMRI, PSMA-PET/CT detected no significant nor focal uptake within the prostate gland even at delayed acquisition (diffuse pattern, SUVmax 3.6). Interestingly, multiple PSMA-avid pelvic and retroperitoneal lymphadenopathies were detected (SUVmax 34) as well as a single, intense focal bone lesion at L3 vertebral body (SUVmax 14, corresponding with initial focal osteoblastic lesion at low-dose CT images-LDCT), and a single focal uptake in a left axillary lymph-node (SUVmax 19). Of note, the latter lymph-node was homolateral to the injection site of recent anti-SARS-Cov2 vaccination and without clearly pathological pattern on LDCT. However, due to its high PSMA expression, it was chosen for ultrasound-guided biopsy and finally diagnosed as Pca metastasis. Conclusion(s): Several malignancies can present with subdiaphragmatic nodal findings, but this is a highly interesting case as, despite the advanced metastatic spread at initial presentation, the primary Pca was detected by none of the diagnostic techniques. The importance of [68Ga]Ga-PSMA-PET/ CT was to rapidly pave the way to reach the final diagnosis by selecting the unusual axillary lesion with elevated PSMA expression as the target biopsy for a mini-invasive approach optimizing patient management;in addition, it was able to detect a single PSMA avid sclerotic lesion typical for initial bone spread of PCa.

A CASE OF ROSAI-DORFMAN DISEASE PRESENTING AS A PULMONARY ARTERY MASS

SESSION TITLE: Pathology Under the Microscope SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm INTRODUCTION: Rosai-Dorfman disease (RDD) is a rare, idiopathic, nonmalignant lymphohistiocytic proliferative disorder that presents with lymphadenopathy and less commonly with extranodal involvement (1). This is a case of a patient found to have a pulmonary artery mass and bone lesions consistent with RDD. CASE PRESENTATION: A 33-year-old female with COVID pneumonia presented with one week of dyspnea, myalgias, and chills. She developed hypoxia requiring 2L of supplemental oxygen. Physical exam was benign and without lymphadenopathy. CT angiography demonstrated a well circumscribed 2.3cm x 2.1cm eccentric filling defect concerning for a pulmonary embolism versus vascular mass. She had a normal troponin and brain natriuretic peptide. Echocardiogram showed normal left ventricular ejection fraction and right ventricular size and function. Lower extremity dopplers were negative for acute deep venous thrombosis. Cardiac MRI demonstrated a mass in the posterior aspect of the proximal main pulmonary artery superior to the pulmonic valve measuring 1.9cm x 1.6cm that was consistent with a benign cardiac tumor. Patient was discharged and underwent sternotomy and excision of the mass one week later. Pathology showed histiocytosis consistent with RDD. Post-operatively she developed recurrent fevers and imaging showed bony lesions in her lumbar spine, maxilla, and skull base. Pathology from an IR guided biopsy of the lumbar lesion was suggestive of RDD. DISCUSSION: RDD is a rare, nonmalignant lymphohistiocytic proliferative disorder that usually involves lymph nodes. Concurrent nodal and extranodal involvement has been reported in 43% of cases while isolated extranodal involvement has been reported in 23% of cases. Common extranodal sites include cutaneous, soft tissue, upper respiratory tract, bone, and central nervous system (1). There are only a few cases reported of pulmonary artery involvement. These cases include a patient with RDD invading the pulmonary trunk and aorta who required surgical resection and reconstruction due to impending right ventricular failure (2) and a young woman with RDD causing nearly complete obstruction of the main pulmonary artery resulting in severe pulmonary hypertension and heart failure who required debulking (3). This case demonstrates RDD involving the main pulmonary artery and bones which was incidentally discovered when the patient was hospitalized for COVID pneumonia. RDD has a benign course but when the pulmonary artery is involved, patients often require surgical excision. CONCLUSIONS: RDD is a benign proliferation of histiocytes that most commonly presents with cervical lymphadenopathy. Extranodal involvement has been reported but pulmonary artery involvement is rare. RDD has a benign course, but pulmonary arterial involvement often requires surgical excision. Reference #1: Gaitonde, S. (2007). Multifocal, extranodal sinus histiocytosis with massive lymphadenopathy: an overview. Archives of pathology & laboratory medicine, 131(7), 1117-1121. Reference #2: Prendes, B. L., Brinkman, W. T., Sengupta, A. L., & Bavaria, J. E. (2009). Atypical presentation of extranodal Rosai-Dorfman disease. The Annals of thoracic surgery, 87(2), 616-618. Reference #3: Walters, D. M., Dunnington, G. H., Dustin, S. M., Frierson, H. F., Peeler, B. B., Kozower, B. D., … & Lau, C. L. (2010). Rosai-Dorfman disease presenting as a pulmonary artery mass. The Annals of thoracic surgery, 89(1), 300-302. DISCLOSURES: No relevant relationships by Veena Dronamraju Advisory Committee Member relationship with Nabriva Please note: 1 day Added 03/14/2022 by Rohit Gupta, value=Consulting fee No relevant relationships by MARUTI KUMARAN no disclosure on file for Bilal Lashari;No relevant relationships by Parth Rali No relevant relationships by Stephanie Tittaferrante No relevant relationships by Yoshiya Toyoda

Tumor marker study in pleural fluid and tumor heterogeneity

Background-aim: Tumor markers (TM) in body fluids have been studied for years and several authors have proposed different cut-off. An apparently more accurate strategy is the one proposed by Molina et al. considering that the ratio TM in fluid with regard to TM in serum >1.2 indicates local production in the pleura, however if the ratio is <1.2 the presence of TM in the fluid would be explained by serum extravasation. Despite enough evidence to manage this biomarkers in body fluids, the practice is not widely extended in the clinical setting yet. Methods: AFP, CA19.9, CA15.3, CEA, CA125, PSA and SCC were analyzed in Alinity i platform (Abbott diagnostics) HCG and NSE was performed in Cobas e411 (Roche diagnostics). Results: Here we describe the case of a 69-year-old patient attending the Emergency Room due to pain in both hemythoraxes. Also remarkable was a wasting syndrome (5 kg weight loss in the past month). In Emergency blood analysis: VSG 50, PT 75%, DD 765 ng/mL, ferritin 368 ng/mL and LDH 385 U/L were outsdanding. Thorax radiology showed a pleural effusion. The patient was diagnosed with COVID19 bronchitis.TC scan evidenced pleural solid metastasis, multiple bone lesions and hepatic M1. Serum TM: AFP, CA19.9, PSA, NSE, SCC and HCG were normal. CA125 2992,60 U/mL (<35), CA15.3 614,70 U/mL (<32), CEA 400.82 ng/mL (<5). Pleural fluid TM: CEA 284.32 ng/mL;CA15.3 2210.3 U/mL. TM ratio: CA15.3: 3.6 (>1.2) this result indicates local synthesis of CA15.3, therefore pleural metastasis;CEA: 0.7 (<1.2) indicates that the CEA found un the fluid was extravasated from serum. Pathological examination was only positive for CK7 and mixt CK. All other markers were negative. It was concluded to be an undifferentiated carcinoma, cytologically reminding of an adenocarcinoma. Due to TTF1 and napsine negativity lung neoplasm could not be discarded.The patient was diagnosed with undifferentiated lung cancer stage IV. Conclusions: This a good example of different molecular patterns reflecting tumor heterogeneity evidenced by protein expression by each lesion: Pleural metastases expressed high amounts of CA15.3, however not CEA. Hepatic metastases and probably main tumor in the lung expressed CEA and CA15.3. It is arguable whether CA15.3 was expressed at lower quantities from the main tumor or the dilution of the protein in the bloodstream results in lower concentrations in relation to the ones found in the pleura.

Acute respiratory distress syndrome after exposure to carfilzomib (KYPROLIS)

Case Report Introduction Plasma cell leukemia is very rare and an aggressive form of leukemia with a poor prognosis. Interim analysis of a phase II trial (EMN12/HOVON 129) using carfilzomib, lenalidomide, and dexamethasone (KRd) in patients with PCL ≤65 years showed a very good partial response or greater response in 80% with 33% achieving at least a complete response. Carfilzomib (Kyprolis TM) is a proteosome inhibitor and is associated with ARDS and acute respiratory failure in 2% of the cases per FDA package insert. We present a case report of acute respiratory distress syndrome presumed to be potentiated 2/2 to carfilzomib infusion. Case A 58-year-old male with a history of hypertension, recent COVID-19 infection and new diagnosis of untreated Plasma Cell Leukemia presented to our hospital with worsening chest pain, fatigue and dyspnea. Vitals on admission were notable for BP 158/88, HR 101, Tmax 99F and sating 100% on room air. Peripheral blood exam showed WBC: 27.7 x109/L, Hb: 8 gm/dl, platelet: 121000, corrected calcium: 13.3 mg/dl, creatinine: 1.16 mg/dl, total protein:11 g/ dl, uric acid: 8.2 mg/dl, B-2 micro globulin: 5.8 mg/L, Mspike: 5.6 g/dl;IgA lambda type. CT Chest abdomen pelvis revealed diffuse lytic bone lesions. Due to inability to obtain bone marrow biopsy from limited resources after Hurricane Ida and aggressive nature of the cancer, treatment was initiated based off a previous flow cytometry from the peripheral blood which showed 55% plasma cells. Patient started on chemotherapy with Cyclophosphamide, Carfilzomib, and dexamethasone with plans to change to Revlimid from cycle 2. He was also started on fluid hydration and Zometa for hypercalcemia. Patient also received aggressive blood pressure control with metoprolol, amlodipine and IV labetalol as needed. After 2nd dose of Kyprolis, he developed acute hypoxic respiratory distress and was initiated on Bipap. Chest Xray was concerning for fluid overload and/or evolving pneumonia. He was supported with diuretics and broad-spectrum antibiotics;however, he eventually was intubated. He was also started on high dose steroids. Repeat CT chest was negative for thrombosis, but showed extensive bilateral pleural -parenchymal opacities. He had a bronchoalveolar lavage with no obvious infection. Over the next 2 days, patient showed improvement and eventually self-extubated. After his recovery, we continued chemotherapy with Kyprolis and he has tolerated it without issues. Discussion The etiology of ARDS is likely multifactorial, however Kyprolis may have played a major role in his decompensation mainly due to the timing and known side effects of the medication. Based on a study from 2018, only 5 case reports of Kyprolis-associated non-infectious progressive lung injury were found at that time. Clinicians should be mindful of Kyprolis induced lung injury and emphasize the need for tight blood pressure control and careful administration of intravenous fluids to decrease the possibility of lung injury.

Bortezomib-Pomalidomide-Dexamethasone (VPD) As Novel Induction Therapy in Newly-Diagnosed Multiple Myeloma: Early Safety Data from an Ongoing Single Arm Phase-II Investigator-Initiated Clinical Trial (PRIME Study)

Introduction: Pomalidomide is a third-generation immunomodulatory drug approved for relapsed and/or refractory Multiple Myeloma (RRMM). In the phase 3 OPTIMISMM trial, pomalidomide, bortezomib, and dexamethasone demonstrated superior efficacy in patients with RRMM. PRIME study (CTRI/2019/10/021618) is testing this combination in Newly Diagnosed Multiple Myeloma (NDMM) Aim: To determine safety of Pomalidomide in combination with Bortezomib and dexamethasone (VPD) in NDMM Study design: A prospective, single arm, phase II study from a tertiary center. Both transplant eligible and ineligible patients with NDMM aged between 18-70 years are being recruited in the study. Patients with Plasma cell leukemia, POEMS and amyloidosis were excluded. The regimen consists of weekly Bortezomib 1.3mg/sq.m (subcutaneous), Tab. Pomalidomide 2-4mg once daily for 21days, and Tab Dexamethasone 20mg twice weekly, with the cycle repeating every 28 days, 9-12 cycles. Here we report the adverse events (AE) by NCI CTCAE v5.0, upon recruiting 26 patients, as predetermined in the study. Results: Of the proposed 45-50 patients, 26 patients were enrolled in the study between April 2020 to May 2021 and 23 (88.4%) have completed 4 cycles of VPD. The median age is 55years (18-70), and gender ratio 1:1. At disease presentation, bone lesions were the commonest (96.2%, n=25), IMWG high risk cytogenetics were seen in 42.4% (n=11), RISS-2 in 69.3% (n=18), IgG kappa paraproteinemia in 54% (n=14) patients and ECOG performance score 2-3 in 57.6%(n=15). Ten (38.5%) patients have completed 9 cycles, and 3 underwent auto-transplant (between Cycle 4 & 6). Protocol adherence was 96.1% (25/26 patients). Table-1 shows drug-induced toxicity, hematological toxicities were the commonest. Two patients withdrew consent in view of bortezomib-induced peripheral neuropathy. Serious adverse events (SAE) were reported in 9 (34.6%) patients and were considered unrelated to the regimen by the safety committee (PSVT=1, Bony pain=2, dyspnea=1, pneumonia=1, constipation=1, diarrhea=1, hypotension=1) and one death due to SARS-CoV2 pneumonia. Treatment delays of 2 weeks in 4 patients (SARS-CoV2 = 3, Syncope = 1) After 4 cycles (n=23), 6 (26%) patients were in stringent Complete Response (sCR), 17(74%) in Very Good partial response (VGPR) and 13 (56.5%) are Measurable Residual Disease (MRD) negative. Of 10 patients who completed cycle 9, 9 were MRD negative and 1 showed disease progression. Conclusion: Safety data from the PRIME study demonstrates that VPD regimen has a favorable tolerance profile in patients with NDMM. Early efficacy signals are encouraging, and recruitment continues. [Formula presented] Disclosures: Radhakrishnan: Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees;Emcure Pharmaceuticals: Research Funding;Intas Pharmaceuticals: Research Funding;Janssen India: Honoraria;NATCO Pharmaceuticals: Research Funding;Novartis India: Membership on an entity's Board of Directors or advisory committees;Roche India: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;AstraZeneca India: Honoraria, Speakers Bureau;Bristol-Myers-Squibb India: Membership on an entity's Board of Directors or advisory committees, Research Funding;Cipla Pharmaceuticals India: Research Funding;Aurigene: Speakers Bureau. Garg: Dr Reddys Laboratories: Honoraria, Speakers Bureau. Nair: Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Intas pharmaceuticals: Honoraria, Speakers Bureau;Mylan pharmaceuticals: Honoraria;Novartis India: Honoraria;Fresenius Kabi India: Honoraria;Cipla Pharmaceuticals: Honoraria, Speakers Bureau;Janssen India: Honoraria, Speakers Bureau. Chandy: Janssen: Honoraria;Pfizer: Honoraria;Intas Pharmaceuticals: Research Funding.

Bone biology and COVID-19 infection: Is ACE2 a potential influence factor?

The outbreak of coronavirus disease 2019 (COVID-19) has posed a severe threat to global health management system since it has been detected in the human body. This pandemic was prompted by severe acute respiratory syndrome coronaviruses 2 (SARS-CoV-2) and rapidly developed into a public emergency with an alarming increase in cases and deaths. The increasing explorations to SARS-CoV-2 infection guide us to consider whether bone lesion is followed by this pathologic process. We especially focus on the underlying pathobiology that SARS-CoV-2 possibly mediated in bone remodeling and analyze the association of bone destruction with ACE2 in COVID-19 incidence, for preferable understanding the pathogenesis and providing necessary clinical management in orthopedics.