History Of Multiple Myeloma Research Articles

Carfilzomib-Based Regimen and Cardiotoxicity in Multiple Myeloma: Incidence of Cardiovascular Events and Organ Damage in Carfilzomib-Dexamethasone versus Carfilzomib-Lenalidomide-Dexamethasone. A Real-Life Prospective Study.

Carfilzomib-mediated cardiotoxicity in multiple myeloma (MM) is a well-established adverse effect, however limited data are available on the comparison of cardiovascular complications in patients treated with Carfilzomib-dexamethasone (target dose of K 56 mg/m2) versus Carfilzomib-lenalidomide-dexamethasone (target dose of K 27 mg/m2) beyond controlled trials. A total of 109 patients were enrolled, 47 (43%) received Kd and 62 (57%) KRd. They then underwent a baseline and follow-up evaluation including trans-thoracic echocardiography and arterial stiffness estimation. All types of cardiovascular and hypertensive events occurred more frequently in the Kd group compared with the KRd (59% vs. 40% and 55% vs. 35.5% patients, respectively, p ≤ 0.05), with higher incidence of hypertensive. The time of onset of any type of CVAE, and of major and hypertensive events was shorter in the Kd regimen (p ≤ 0.05). At follow-up, Kd patients more frequently developed signs of cardiac (decline of global longitudinal strain) and vascular organ damage (rise of pulse wave velocity), as compared with KRd. Despite the older age, longer history of MM and longer period of pre-treatment of Kd patients, these factors did not increase the probability of incidence for all types of cardiovascular events at multivariate analysis (p > 0.05). In conclusion, the Kd regimen showed greater cardiovascular toxicity and earlier onset of events with respect to KRd. Thus, a closer and thorough follow-up should be considered.

1244: CAN ADMINISTRATION OF HIGH-DOSE HYDROXOCOBALAMIN IMPROVE OUTCOMES IN REFRACTORY SEPTIC SHOCK?

Introduction: Multiple high dose vasopressors are often required to sustain life in critically ill patients but are unfortunately associated with high mortality (>50%) and morbidity. This case discusses the potential benefit in adding high dose IV hydroxocobalamin (B12) therapy (5g) to potentially reduce the use of additional vasopressors and their impact on morbidity and mortality. Description: A 72-year-old immunocompromised man with history of multiple myeloma, refractory to multiple lines of therapy, prior CAR-T treatment with now stable disease was found down, covered in feces. He was admitted to the medical ICU for severe septic shock secondary to pseudomonas bacteremia. The patient progressed to Multiorgan failure requiring mechanical ventilation, broad spectrum antibiotics, and multiple vasopressors at maximum doses. Echocardiogram (echo) showed biventricular heart failure with ejection fraction (EF) reduced from 64% 4 months prior to 25%. The bronchoalveolar lavage sample grew Pseudomonas aeruginosa, and antibiotics were adjusted. He was requiring norepinephrine (NE) at 0.3 mcg/kg/min, vasopressin (vaso) at 0.04 units/min, epinephrine (epi) to 0.3 mcg/kg/min, angiotensin II (ATII) between 10-40 ng/kg/min, and dobutamine (dobut) as high as 12.5 mcg/kg/min for 47 hours before B12 administration. The patient remained hypotensive (MAP < 65 mmHg) with maximal vasopressors. The left hand become cold and discolored, his legs and abdomen became severely mottled. Due to lack of response to therapy a trial of 5g B12 was given. There was improvement in the patient’s blood pressure. NE and ATII were stopped within 24 hours, Epi and vaso stopped within 96 hours, and dobut was weaned gradually. He was extubated on day 12. EF improved to 60% with normal right ventricular function on day 14. The skin gradually returned to normal. The left-hand fingers appeared better perfused with only the tip remaining discolored. Discussion: Bacterial endotoxins released in sepsis induce nitric oxide synthase, activating cGMP, which causes subsequent smooth muscle inhibition and vasodilation. B12 scavenges nitric oxide decreasing vasodilation. Use of B12 as an adjuvant to traditional vasopressor therapy could help reduce morbidity and mortality in septic shock by reducing overall dose/duration of vasopressors.

Reconstructing the Genomic History of Multiple Myeloma Precursor Disease: Novel Insights and Clinical Applicability

Introduction Early indolent stages of Multiple Myeloma (MM), which include monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), are heterogeneous diseases with overall rates of progression of 1% to 10% per year. Mutations present in MGUS and SMM have been characterized by our group and others and improve current risk models. However, whether any genomic events are sufficient for an MGUS or SMM to transform to MM remains an open fundamental question. To address this, we sequenced the largest cohort of MGUS and SMM genomes to date starting with a low-input DNA template, enriching for low burden of disease compared to previous studies. We report the translational implications of a large-scale characterization of indolent stages of MM after 2 years of follow-up. Methods Bone marrow (BM) samples were collected from 130 patients with MGUS and SMM after informed consent for research use (IRB #14-174). Plasma cells were selected from BM samples using CD138+ magnetic beads before DNA purification and library construction. Tumor and matched germline libraries were whole-genome sequenced (WGS) to 60X and 30X coverage respectively on NovaSeq 6000 S4 flowcells at the Genomics Platform of the Broad Institute. Analysis was performed with methods from the Cancer Program of the Broad Institute. All structural variants were manually reviewed and compared to fluorescence in situ hybridization (FISH) clinical laboratory reports. Results The median age of participants was 62 (range, 37 to 87), with 52% female. At the time of BM sampling, all patients were untreated; 24 patients diagnosed with MGUS (18%) and 106 diagnosed with SMM (82%) were homogeneously distributed across the IMWG 2/20/20 risk stratification stages (Low-risk: 32%, Intermediate-risk: 34%, High-risk: 34%). Somatic mutation burden increased with progressive disease staging, with a median of 2,666 single-nucleotide variants in MGUS (range 429-6546), and 3,233, 4,080, and 5,111 in low, intermediate, and high-risk SMM, respectively (range 463-11083, 161-8408, and 2549-7218, respectively, P=0.007). Compared to non-progressors, progressors were found to have an increase of molecular clock signature, symbolizing continuous accumulation of mutations over time (Fold change 2.40, P=0.002), and this difference was independent of patient age and disease stage. Confirming previous studies, APOBEC signature was strongly associated with patients with MAF alterations (t(14;16), t(14;20), median in MAF, 24%, non-MAF, 5.8%, P=3E-5), and uniquely identified in one patient with MMSET t(4;14) translocation. Catastrophic structural variants (SV) such as chromothripsis and chromoplexy were found in 7% of patients across 2/20/20 stages. Complex SVs were strongly associated with clinical progression to symptomatic MM (Odds Ratio (OR) 9.83, CI95%[1.91, 53]). Being statistically independent of risk staging, these events are a potential new risk factor not captured by current clinical models, but successfully characterized by an unbiased genomic assay. In our cohort, MYC was found rearranged with IgL, IgH, and other partners in 9% of patients. Strikingly, all but one case also harbored a RAS hotspot mutation, showing a strong non-random cooperation between RAS and MYC (P=0.005), not previously observed, which translated into increased risk of clinical progression (OR 7.75, CI95%[1.26, 48.8]). Moreover, most MYC-abnormal tumors (translocation or complex rearrangement) were missed by clinical FISH testing. WGS detected >99% of translocations and copy number abnormalities reported by FISH. In clinical reports with unknown translocations, WGS could identify translocation partners, including IgH-MYC and rare IgH-MAFA. In 82% of patients, an increased diagnostic yield was found by WGS compared to FISH using existing models, showing clinical applicability to replace molecular cytogenetics. Conclusion Analysis of the largest cohort of MGUS and SMM genomes to date was able to decipher the genomic history of MM, unraveling events including molecular clock signature, APOBEC, complex SVs, and MYC/RAS cooperation. This can further define a genomic risk model of disease progression independent of clinical tumor burden markers such as 2/20/20. This highlights the potential of WGS to solve the "missing predictability" of current clinical models of progression.

Family History of Hematologic Malignancies and Risk of Multiple Myeloma in Black Americans

Introduction: Multiple Myeloma (MM) is the most common hematologic malignancy in Black Americans. Standardized incidence rates are increasing, consistent with an aging population, and are 2- to 3- fold higher among Black Americans compared to White Americans for reasons that remain unclear. Methods: Using participants enrolled in the Integrative Molecular And Genetic Epidemiology (IMAGE) study of myeloma (955 MM cases; 1,316 sex-, race-, age-, geography- matched controls), we investigated the risk of MM associated with family history of cancer and differences by race. We estimated risk using odds ratios and corresponding 95% confidence intervals adjusted for confounders calculated from logistic regression. Results: Overall, MM risk in cases with a first degree relative affected with any hematologic malignancy was significantly elevated compared to controls (OR=1.36, 95% CI 1.02-1.82; P=0.038). Myeloma risk associated with a family history of MM was higher than the risk associated with any hematologic malignancy (OR=2.13, 95% CI 1.20-3.79; P=0.001), and the magnitude of this effect was greater for Black Americans (OR=4.88, 95% CI 1.90-12.51; P=0.001) than White Americans (OR=1.03, 95% CI 0.45-2.32; P=0.951) with similar relationships observed among first degree relatives with any plasma cell proliferative disorder (ORBlack=5.34, 95% CI 2.11-13.54; P=0.0004 and ORWhite=1.18, 95% CI 0.59-2.37;P=0.642) and with increasing numbers of affected relatives (P-trend=0.001). Conclusions: Findings confirm our previous report that the excess risk of MM observed in Black Americans may be attributed to shared germline and environmental susceptibility. Studies, which include family history of plasma cell proliferative disorders, to determine screening effectiveness in high-risk populations are warranted.

Light-Chain Amyloidosis in Sweden (2011-2019): Incidence, Disease Burden, and Clinical Outcomes in Real-World Patients

Introduction: Light-chain (AL) amyloidosis is a rare plasma cell disorder characterized by organ damage caused by deposits of light-chain amyloid fibrils. While prior research indicates that outcomes for AL patients have improved with the adoption of novel anti-plasma cell combination therapies as standard of care, there are limited population-based data characterizing outcomes in contemporary real-world patients with AL. In the present study, Swedish registry data were used to characterize AL incidence trends, patient clinical characteristics, and outcomes in real-world patients newly diagnosed with AL. Methods: Data came from six nationwide population-based registers provided by the National Board of Health and Welfare in Sweden and Statistics Sweden and linked by unique personal identity number. Patients ≥18 years of age and newly diagnosed with AL were identified on the basis of having ≥2 diagnosis codes for amyloidosis (ICD-10-SE codes E85.4x, E.85.8x, E85.9) from 1/1/2011 to 12/31/2019 plus ≥1 of the following: (1) receipt of anti-plasma cell therapy, (2) an amyloidosis diagnosis made in a hematology/oncology clinic, and/or (3) a diagnosis code specific to AL (E85.8A). Patients with a prior history of amyloidosis or specific diagnosis codes or treatments consistent with non-AL amyloidosis etiologies were excluded. For each newly diagnosed AL case, individuals from the general population without any type of amyloidosis were randomly selected and matched with a maximum ratio of 1:5 based on age, sex, calendar year, and county. Key measures of interest included AL incidence and prevalence, baseline patient characteristics, burden of and interventional procedures for cardiac and renal complications, and OS overall and by major organ involvement. Risks of incident cardiac and renal failure and OS were quantified with the Kaplan-Meier (KM) estimator; log-rank tests were used to evaluate the differences in survival and Cox regression was used to provide an estimate of the hazard ratio (HR). Patients were followed until date of death or the database cut-off date (12/31/2019), whichever occurred first. Results: 846 Swedish patients newly diagnosed with AL (median age 70yr, 41% female) and 4,227 demographically matched controls were identified. During the study period, there was an increase in the incidence of AL from 10.5 cases per million in 2011 to 15.1 cases per million in 2019 (test for trend: p<0.001; Figure 1A). At initial diagnosis, 48%, 33%, and 18% of AL patients had evidence of cardiac, renal, and neurologic involvement, respectively; 10% had a history of multiple myeloma. Relative to the non-AL controls, at baseline AL patients had a significantly higher mean Charlson Comorbidity Score (1.7 vs 0.4; p<0.001) and higher rates of cardiac failure (30% vs 5%; p<0.001) and renal failure (12% vs 2%; p<0.001). In AL patients, the KM estimated risks of incident cardiac and renal failure at 5 years following initial diagnosis were 38% and 28%, respectively. Median OS for AL patients was 4.7 years vs. not reached in non-AL controls (HR: 5.8, 95% CI [5.0, 6.7]; Figure 1B). Conclusions: In this contemporary cohort of real-world Swedish patients newly diagnosed with AL, the risks of cardiac failure, renal failure, and all-cause mortality were higher relative to the demographically-matched general population comparison group. In addition, a trend toward an increased incidence of AL was observed during the study period (2011-2019). This trend may reflect greater awareness of AL and an increased likelihood of it being diagnosed and treated in the last years of this time-period. Compared to the median OS of 1.7 years previously reported for Swedish patients newly diagnosed with AL in 1995-2013 (Weiss et al, Am Soc of Hematology, 2015), the median OS of 4.7 years observed for patients newly diagnosed with AL in the present study represents a meaningful improvement. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

S2214 A Rare Case of Secondary Extramedullary Plasmacytoma With Ileocecal Involvement

Introduction: Extramedullary plasmacytomas (EMPs) are a rare type of plasma cell dyscrasia characterized by the neoplastic proliferation of plasma cells in soft tissue.EMPs share characteristics with multiple myeloma (MM) and can present as primary tumors or secondary to other plasma cell neoplasms.Herein we present an extremely rare case of a patient with established MM who was found to have an asymptomatic ileocecal mass with biopsy findings consistent with secondary EMP. Case Description/Methods: A 62-year-old female with a past medical history of MM and Ulcerative Colitis (UC) presented to the gastroenterology clinic for evaluation of her UC before consideration of an experimental therapy trial for her refractory MM.On presentation, she denied changes in her bowel habits or blood in her stool. Lab results 2 weeks prior to presentation were significant for leukopenia at 2.9k/uL, normocytic anemia with hemoglobin at 8.5gm/dL, Calcium 8.2 mg/dl, and total protein of 5.7g/dl. Colonoscopy showed nodular, ulcerated mucosa at the hepatic flexure as well as a large polypoid non-bleeding, non-obstructing, non-circumferential mass at the ileocecal valve. Histopathology of the mass returned positive for CD138 Kappa and negative for lambda AE1/AE3, CAM 5.2, GATA3, ER, consistent with a diagnosis of plasma cell myeloma. The patient continued on salvage chemotherapy but passed shortly thereafter (Figure). Discussion: Plasma cell neoplasms (PCNs) involving extra-osseous tissues are known as extramedullary plasmacytomas (EMPs).EMPs are further classified into primary EMPs, which are localized proliferation of clonal plasma cells in the absence of a systemic plasma cell dyscrasia, and secondary EMPs, where there is already a known primary PCN present. To the best of our knowledge, secondary EMP involving the small intestine and cecum is rare and only reported in a handful of case reports.Due to the indolent course of EMPs, nonspecific gastrointestinal manifestations may go undiagnosed in a subset of patients with MM. The prognosis of secondary EMP involving the gastrointestinal tract remains unclear, however, the limited data we have indicates a poor prognosis.On the other hand, novel treatments of MM continue to improve survival rates in patients with MM. As mortality in these patients decreases, the incidence of secondary EMPs is expected to proportionately rise as well. As such, more data is needed to understand how to monitor and treat this patient population for extramedullary involvement in order to generate good outcomes.Figure 1.: Large polypoid non-bleeding, non-obstructing, non-circumferential mass at the ileocecal valve before and after biopsy.

Management of Respiratory Failure in Patients with COVID-19 and Multiple Myeloma

Background: Cancer patients have higher risk of getting COVID-19. Individuals with malignancy who infected COVID-19 often underwent prolonged hospitalization or death. Here, we report respiratory failure management of of COVID-19 patient with multiple myeloma (MM). Case: A 66-year-old man came with complaints of shortness of breath. The patient was intubated and treated in the intensive care COVID. Patients with a history of multiple myeloma and who have chemotherapy cycle. The laboratory results showed an increase in markers of inflammation, hypoalbuminemia, and bicytopenia. The results of the polymerase chain reaction swab were positive. There are 4 managements in this patient, airway management: intubation and ventilator settings using the Lung Protective Strategy principle. Management Breathing: administration of antibiotics according to sputum culture results. Circulation Management: Fluid management using a non-invasive Contractility Index (ICON) monitor. Management of Disability: Spontaneous Awakening Trial (SAT) and Spontaneous Breathing Trial (SBT) when the aggravating disease has been handled. Conclusion: Management of respiratory failure in patients with multiple myeloma and COVID-19 infection is primarily focused on supportive care such as airway management, breathing management, fluid management and disability management.

Invasive Orbital Squamous Cell Carcinoma in a Patient with Multiple Myeloma

Background Orbital squamous cell carcinoma (SCC) is a rare entity. It is often a result of local invasion of SCC originating from the skin, nasopharynx, nasal cavity, paranasal sinuses, conjunctiva, lacrimal glands, or sac or less commonly occurs through hematogenous metastasis. Herein, we report a patient with orbital SCC with a history of multiple myeloma (MM). Case presentation. A 45-year-old woman with a history of MM in the past two years presented to our clinic complaining of gradual right eye proptosis for six months. The relative afferent pupillary defect was detected in the right eye on her examination. Ocular movements of the right eye were limited in all directions. Orbital magnetic resonance imaging demonstrated an infiltrative mass in the right orbit extended from the anterior to the orbital apex and the optic canal. The patient underwent debulking, and a histopathology examination revealed SCC results. No other secondary site was found to be the origin of the tumor. Result The patient underwent chemotherapy and subsequent radiotherapy. To our knowledge, this is the first report of concomitant MM and primary orbital SCC.

P226 Bortezomib-induced muscle toxicity mimicking myositis

Abstract Background/Aims Novel drugs such as bortezomib are proteasome inhibitors that are used to treat multiple myeloma. Bortezomib induces apoptosis of rapidly dividing, metabolically active cells with extensive protein synthesis. Literature review shows two case reports of bortezomib-induced reversible muscle toxicity and motor neuropathy, used to treat multiple myeloma (MM) with persistently normal creatine kinase. In a single-centre prospective study, 14 out of 24 patients with symptomatic MM were treated with bortezomib and, among these, seven developed proximal lower limb weakness with complete resolution of symptoms after discontinuation of bortezomib as depicted in our case. We present a case of myositis mimic which was triggered by the use of immunotherapy Bortezomib to treat multiple myeloma. Methods An 81-year-old Caucasian gentleman was admitted with proximal lower limb weakness. He had a background history of multiple myeloma, treated with melphalan, prednisolone and bortezomib commenced in September 2019. Following his fourth cycle in January 2020, he noted proximal lower limb weakness and was referred to Rheumatology. He had MRI of the spine which did not reveal any cord compression. His prednisolone was stopped. On further questioning, there were no features to suggest connective tissue disease, inflammatory arthritis or vasculitis. On examination power was reduced to 4/5 in the proximal muscles of lower limb affecting his mobility. Rest of the examination was unremarkable. Results All bloods including creatinine kinase, autoimmune profile and inflammatory markers were normal. Magnetic resonance imaging (MRI) of the thighs showed diffuse fatty atrophy within all muscle groups of the thighs with low grade oedema within the vastus lateralis and intermedius particularly of the left thigh when compared to the right. The appearances were in keeping with inflammatory myositis, without any abscess formation. Electromyography showed abnormal signals with neurogenic and myopathic changes. Nerve conduction studies showed moderate length-dependent axonal peripheral neuropathy. Following his review, investigations and discussion between Rheumatology and Haematology, it was believed that his lower limb weakness was likely related to his bortezomib and the decision was made to stop bortezomib therapy. He was followed up in Rheumatology and Haematology clinic after stopping bortezomib with improvement of lower limb weakness and mobility. His creatinine kinase and inflammatory markers remained persistently normal. Muscle biopsy was not considered as there was enough evidence to suggest it was bortezomib induced muscle toxicity. Conclusion We present a case of myositis mimic whose symptoms completely resolved on stopping bortezomib. As this is one of the rare and early complications of bortezomib we suggest that patients treated with bortezomib should be monitored for muscle weakness. Disclosure G. Ansari: None. Z. Alkutobi: None. A. Nandagudi: None.

Non-Invasive Physical Plasma Treatment after Tooth Extraction in a Patient on Antiresorptive Medication Promotes Tissue Regeneration

Postoperative tissue regeneration can be negatively affected by bisphosphonate administration, especially in patients with oncologic diseases. A serious complication of bisphosphonate therapy is the medication-related osteonecrosis of the jaw (MRONJ), which can be observed mainly after dental surgery. MRONJ is a progressive destruction of the bone that requires patients to stay in hospital for extended periods of time. For this reason, primary wound closure is particularly important in surgical procedures. In the case of wound dehiscence, there is a very high risk for MRONJ. In recent years, non-invasive physical plasma (NIPP) has become known for improving wound healing on the one hand, but also for its promising efficacy in cancer therapy on the other hand. We report on a 63-year-old patient with a history of multiple myeloma and receiving zoledronate, who developed wound dehiscence after tooth extraction. NIPP treatment resulted in complete epithelialization of the entire wound dehiscence. In conclusion, the use of NIPP in patients receiving antiresorptive drugs seems to support tissue regeneration and thus could be an important tool for the prevention of MRONJ.

Transplant Onconephrology in Patients With Kidney Transplants.

Cancer is a leading cause of death in patients with kidney transplantation. Patients with kidney transplants are 10- to 200-times more likely to develop cancers after transplant than the general population, depending on the cancer type. Recent advances in cancer therapies have dramatically improved survival outcomes; however, patients with kidney transplants face unique challenges of immunosuppression management, cancer screening, and recurrence of cancer after transplant. Patients with a history of cancer tend to be excluded from transplant candidacy or are required to have long cancer-free wait time before wait-listing. The strategy of pretransplant wait time management may need to be revisited as cancer therapies improve, which is most applicable to patients with a history of multiple myeloma. In this review, we discuss several important topics in transplant onconephrology: the current recommendations for pretransplant wait times for transplant candidates with cancer histories, cancer screening post-transplant, post-transplant lymphoproliferative disorder, strategies for transplant patients with a history of multiple myeloma, and novel therapies for patients with post-transplant malignancies. With emerging novel cancer treatments, it is critical to have multidisciplinary discussions involving patients, caregivers, transplant nephrologists, and oncologists to achieve patient-oriented goals.

Renal Amyloidosis: A Clinicopathological Study From a Tertiary Care Hospital in Pakistan.

IntroductionSystemic amyloidosis can affect any organ in the body, but the kidney is the most commonly involved site. It is characterized by the extracellular deposition of insoluble fibrillar proteins. Amyloid deposits can be identified histologically by Congo red stain, which gives apple-green birefringence under polarized light. Typing of renal amyloidosis is done by direct immunofluorescence on frozen tissue. The most common types of amyloidosis seen in renal tissue are amyloid light chain (AL) primary amyloidosis and amyloid A (AA) secondary amyloidosis. Although primary amyloidosis is considered the most common type in western countries, however, in the subcontinent region, secondary amyloidosis is more common.The spectrum of signs and symptoms in renal amyloidosis is variable including isolated proteinuria, nephrotic syndrome, hypertension, hypotension, and renal insufficiency. The present study aims to evaluate the incidence and aetiology of various types of renal amyloidosis, determine their distribution within the kidney, and study various clinicopathological features.ObjectiveThe present study aims to evaluate the aetiology and clinicopathological profile of renal amyloidosis, determine its various types, and their distribution within the kidney.Materials and methodsThis retrospective cross-sectional study was conducted from 1st January 2013 to 31st December 2020 at the Department of Histopathology, Shifa International Hospital (SIH), Islamabad. All renal biopsies diagnosed as renal amyloidosis were included in the study. Data were analysed using SPSS version 23 (IBM Corp., Armonk, NY). Frequency and percentages were calculated for qualitative variables, and mean and standard deviation were calculated for quantitative variables.ResultsA total of 131 cases were diagnosed with renal amyloidosis during the study period of eight years (from 1st January 2013 to 31st December 2020) at SIH. The age range varied from 17 to 82 years. The mean age of the patients was 45 ± 16.33 years. Out of 131 patients, 82 (62.6%) were males and 49 (37.4%) were females. Amongst them, 72 (54%) cases were diagnosed with secondary AA amyloidosis and 16 (12%) cases were diagnosed with primary AL amyloidosis. The rest of the cases 43 (34%) were of indeterminate type. The associated conditions in secondary amyloidosis were tuberculosis in 41 (57%), rheumatoid arthritis in 16 (22%), ankylosing spondylitis in five (7%), lymphoma in three (4%), diabetes in two (3%), and chronic osteomyelitis, chronic heart disease, hepatitis, and vasculitis in one case each (1.7%). Out of 16 cases reported with AL amyloidosis, 10 cases (62.5%) had a history of multiple myeloma. The most common clinical presentation was nephrotic syndrome followed by subnephrotic proteinuria, renal failure, and hypertension.ConclusionThe findings of the present study show underlying etiological factors and clinicopathological characteristics of renal amyloidosis. AA amyloidosis is the most common type of renal amyloidosis in our study and tuberculosis is the most common aetiological factor. AL amyloidosis is less frequent in our population.

A New Reality for Multiple Myeloma Renal Failure: US Data Report on Kidney Transplant Outcomes

IntroductionDescribe graft and overall survival outcomes in multiple myeloma (MM) patients who underwent kidney transplant (KT) compared to the general KT population. Patients and MethodsThe Organ Procurement and Transplantation Network/National United Network for Organ Sharing (OPTON/UNOS) database was analyzed from 1988 to 2019 with R 4.00 and the 2013-2017 United States Renal Data System (USRDS) was surveyed for incidence and mortality of MM ESRD. ResultsUSRDS analysis revealed 961 patients diagnosed with ESRD due to MM on average annually, accounting for 0.8% of the ESRD population. Without KT, 44.4% of MM patients died in the first year of renal replacement initiation. OPTON/UNOS analysis identified 218 MM KT patients, compared to 490,089 patients without MM. There was no difference in graft survival between MM KT and the general population (P-value = .13, HR = 1.19 [0.95, 1.49], 95% CI). Median graft survival in MM KT was 2683 days (7.4 years). KT patients with MM had a higher risk for death (P-value = <.0001, HR = 1.83 [1.41, 2.37], 95% CI), and median overall survival was 3076 days (8.4 years). Survival difference was lost when comparing patients ≥50 years (P-value = .42, HR = 1.14 [0.83, 1.56], 95% CI). ConclusionPatients with MM renal failure who underwent KT had equivalent graft and age-matched overall survival compared to the general KT population. Therefore select patients with MM renal failure have potential for excellent KT outcomes, should be considered for transplantation when feasible, and should not be excluded from KT based on a history of MM.

Amyloid deposition in oral cavity and larynx, a single institute experience

Abstract Introduction/Objective Amyloidosis is characterized by extracellular accumulation of insoluble amyloid fibril. Amyloid deposition in the head and neck area is rare. Methods/Case Report In this study, we reviewed 34 specimens from 26 patients including: 18 specimens from the larynx and/or pharynx (13 patients) and 16 specimens from the oral cavity (13 patients). The clinical presentation, related laboratory results, and pathologic finding were reviewed. Results (if a Case Study enter NA) Within the 18 laryngeal specimens were: 10 glottic, 4 supraglottic, 3 nasopharyngeal or pharyngeal wall, and 1 subglottic. Of the 16 cases from oral cavity there were 9 lingual, 3 labial, 2 palatine, 1 tonsillar, and 1 alveolar ridge. Ten out of 13 patients with laryngeal amyloid deposition had protein electrophoresis performed and only 3 of the patients had monoclonal light chain detected. Among these three patients, one had multiple myeloma, one had lymphoplasmacytic lymphoma and one had the diagnosis of plasma cell dyscrasia. Interestingly, in the patients with oral cavity amyloidosis, 10 out of 11 patients tested had abnormal findings. Six of the patients had monoclonal light chain, two demonstrated monoclonal peak of IgG kappa, one with IgG lambda and one with IgA lambda. Among these 10 patients, 6 of them had biopsy-proved or history of multiple myeloma, one patient had marginal zone lymphoma, two patients had systematic amyloidosis. Only one patient did not have any malignancy or systematic involvement identified. Conclusion In our small cohort, the most common location of amyloid deposition in the larynx is glottis. When it involves the oral cavity, tongue is the most common location. Compared to the larynx, amyloid deposition in the oral cavity tends to be associated with hematopoietic malignancy or systematic involvement, although this finding needs to be confirmed by a larger scale of study.

EXTRAMEDULLARY PULMONARY PLASMACYTOMA AS A COMPLICATION OF RELAPSED MULTIPLE MYELOMA

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Fellow Case Reports INTRODUCTION: Extramedullary plasmacytoma (EMP) are rare manifestations of multiple myeloma (MM). We report a case of pulmonary EMP presenting as hilar mass. CASE PRESENTATION: A 51 year old female presented with hearing loss and right facial palsy. Medical history was significant for MM diagnosed 2 years prior, treated with bortezomib-prednisone therapy. 6 months ago, thoracic spine plasmacytoma were found requiring surgical resection and local radiation. Remission was perceived and she was maintained on Thalidomide. MRI brain and spine revealed meningeal enhancement with lytic bony lesions, concerning for metastatic disease. CT chest abdomen pelvis revealed a 4.5 x 5.5 cm right hilar mass with complete right lower lobe (RLL) bronchus occlusion, post-obstructive pneumonia, right pleural effusion, pleural thickening and nodularity. She underwent bronchoscopy with endobronchial biopsy of RLL bronchial nodules and EBUS guided transbronchial needle aspiration of right hilar mass. Pathology was consistent with plasma cell myeloma with plasmablastic features. Given her MM history and absence of EBV, primary plasmablastic lymphoma was less likely. A bone marrow biopsy showed >10% myeloma cells, thus her diagnosis was consistent with relapsed MM with extramedullary plasmacytoma (EMP) rather than primary pulmonary plasmacytoma (PPP). Subsequently she underwent systemic and intrathecal second line chemotherapy, but her course was complicated by rapidly progressive refractory disease and patient chose to pursue hospice care. DISCUSSION: EMP are seen in 7 % patients with MM at the time of diagnosis, whereas another 6% develop it later in the course of illness; these portend poor prognosis. Among them, pulmonary EMP are extremely rare. Other pulmonary complications of multiple myeloma include pneumonia, including organizing pneumonia like consolidation, multiple pulmonary nodules, interstitial infiltrates and pleural thickening and effusion. In contrast, primary solitary extramedullary plasmacytoma is a rare discrete plasma cell neoplasm within soft tissue, without bone marrow involvement or other systemic features of MM. They commonly occur in the aero-digestive tract, of which solitary PPP is a rare type. PPP have better prognosis and longer survival rates compared to EMP associated with MM. Their management also differs, EMP associated with MM are treated aggressively with chemotherapy and local radiation or surgery as needed, whereas solitary PPP are treated with radiation only. CONCLUSIONS: Knowledge of pulmonary EMP and its clinical course is important for physicians, such that the etiology of pulmonary abnormalities in patients with multiple myeloma are evaluated and determined in order to ensure appropriate therapy and patient counseling. REFERENCE #1: Bladé J, et al. Soft-tissue plasmacytomas in multiple myeloma: incidence, mechanisms of extramedullary spread, and treatment approach. J Clin Oncol. 2011;29(28):3805-3812 REFERENCE #2: Varettoni M, Corso A, Pica G, Mangiacavalli S, Pascutto C, Lazzarino M. Incidence, presenting features and outcome of extramedullary disease in multiple myeloma: a longitudinal study on 1003 consecutive patients. Ann Oncol. 2010;21(2):325-330. doi:10.1093/annonc/mdp329 REFERENCE #3: Prasad R, Verma SK, Sodhi R. Multiple myeloma with lung plasmacytoma. Lung India. 2011 Apr-Jun; 28(2): 136-138. DISCLOSURES: No relevant relationships by Jyotirmayee Lenka, source=Web Response No relevant relationships by Naman Sharma, source=Web Response

Découverte fortuite d’une récivide myélomateuse lors d’une scintigraphie osseuse réalisée dans le cadre d’une suspicion d’algodystrophie

We report the case of a 51-year-old patient with a history of multiple myeloma in remission after several courses of chemotherapy and an autologous transplant in April 2019, referred by the pain center of the hospital in December 2020 for the performing of a bone scintigraphy in the context of a suspected algodystrophy of the left upper limb, after surgery for a cervical disc herniation in September 2020. Early whole body acquisition following the injection of 630 MBq of 99mTc-sodium oxidronate demonstrated an intense hyperhemic mass in the left shoulder, associated with diffuse hyperemia in the rest of the left upper limb. Hybrid SPECT-CT imaging confirmed the presence of a large tissue density mass associated with major lysis of the left humeral head. There was also a diffuse reactive hyperfixation of the entire left upper limb as well as two unknow lytic lacunar frontal hyperfixing lesions. Faced with these results, the patient also underwent a PET-CT scan with 18F-FDG finding the large left humeral lesion as well as several hypermetabolic osteolytic lesions. The patient was finally hospitalized in internal medicine and presented for regional multidisciplinary meeting (RCP), which concluded in a myeloma recurrence with left humeral plasmacytoma. Although bone scintigraphy is not one of the examinations recommended in the assessment of myeloma (1,2), it has proven to allow the correction of the diagnosis and the detection of recurrence. 18-FDG-PET-CT was found in our case to be a more sensitive examination in the detection of myeloma lesions, allowing a more complete assessment of the disease and the detection of lesions that went unvisualized on bone scintigraphy.

MM-066: Primary Plasma Cell Leukemia: A Rare Entity with Four Cases

Context Primary plasma cell leukemia (PPCL) is a rare hematological malignancy with an incomprehensible pathogenesis and a very aggressive course. Objectives Determining the risk factors that can cause the development of PPCL and affect its course was aimed. Design Four PPCL patients diagnosed at Gulhane Training and Research Hospital between March 2019 and June 2020 were evaluated in terms of laboratory and clinical course retrospectively. Patients or Other Participants The mean age of the patients at the time of diagnosis was 66 years (44–76), and males/females:1/1. None of the patients had a history of multiple myeloma (MM). Results Two patients presented with leukocytosis. Mean WBC was 59.625x103/mL (3800–197,000), average plasma cell in smear was 54.5% (20–100), mean plasma cell was 55,500x103/mL (600–188,000). Leukapheresis was applied to one patient. Anemia was detected in all, mean Hb was 9.9 g/dL. Thrombocytopenia was detected in 3 patients and mean platelet was 101x103m/L. Immunofixation results were IgG lambda in two, free lambda in one, and free kappa in 1 patient. Genetic results could not be reached. One patient was lost to follow-up and 3 patients were given bortezomib-cyclophosphamide-dexamethasone (VCD) in first-line treatment. Two patients died during follow-up, and mean survival was 77 days. One patient who was given 1 cycle VCD and 1 cycle lenalidomide-dexamethasone was lost to follow-up. ASCT could not be planned due to the short life span of the patients. Conclusion Incidence of PPCL is 0.4–1.2/million, progression from MM is seen in 0.5% cases. There is no difference between MM and PPHL in terms of CD38 and CD138 positivity, but CD56 is more frequently positive in MM and CD20 in PCL. CD27 positivity in PCL indicates increased anti-apoptotic activity. Discussion Approximately 150 multiple myeloma patients were followed up in our clinic between the same dates. Secondary PCL cases were not detected, and the fact that all of the diagnosed cases were PPCL created a picture incompatible with the incidence rates reported in the literature. Lambda monoclonality was shown in three of our patients, so it constitutes a feature for PPCL, unlike myeloma. Absence of genetic results is an important lack of our patients. More patients are needed for determination of risk factors in PPCL. It is necessary to identify poor prognostic indicators and urgently undergo transplantation in eligible patients using bortezomib-based treatment regimens.

ANALYSIS OF INCIDENTAL FINDINGS ON PRE-ENDODONTIC CBCT SCANS

<h3>BACKGROUND</h3> Cone beam computed tomography (CBCT) is a widely used imaging modality and is indispensable for diagnosing pathology and assuring favorable treatment outcome. <h3>CASE REPORT</h3> The incidental findings on 5 CBCT scans before endodontic treatment is presented. Patient A (71-year-old white man) reported for retreatment of tooth #3. CBCT revealed missed MB2 on tooth #3; additional findings include nasopalatine canal cyst and internal resorption on tooth #8. Patient B (46-year-old white man) reported for retreatment of tooth #30 and evaluation of tooth #32 for apical periodontitis. CBCT revealed apical radiolucency on tooth #30 and apical PDL widening on tooth #32. Additionally, tooth #27 was impacted and demonstrated external resorption; odontoma was noted distal to #27. Patient C (49-year-old African American woman) presented for retreatment of tooth #4; missed palatal canal, buccal canal with short fill, apical radiolucency, and discontinuity of the buccal cortex were evident. Apical to tooth #3 a radiopacity with a radiolucent rim was noted; the lesion displaced the inferior border of the maxillary sinus and the buccal cortex. This finding was consistent with cemento-osseous dysplasia. Patient D (75-year-old white man) reported with an abnormal feeling around tooth #4; no relevant clinical findings. CBCT revealed an ill-defined radiolucency in the area of tooth #4 and #5 with destruction of the maxillary sinus floor and the lingual and buccal cortical plates. The patient had a history of multiple myeloma. Radiographic and clinical findings were suggestive of a malignant process. Patient E (58-year-old woman) was referred for evaluation of a mandibular radiolucency. CBCT demonstrated a multilocular radiolucency involving teeth #20 to #24; expansion and thinning predominantly involved the lingual cortex. Buccal cortical thinning, expansion, and displacement was noted in the area of tooth #22. The lesion was diagnosed as ameloblastoma. <h3>DISCUSSION/CONCLUSIONS</h3> Incidental findings on CBCT scans include inflammation, cysts, benign and malignant tumors, developmental anomalies, and dystrophic calcification. Providers must be adequately trained to promptly address the abnormalities encountered to ensure the highest standard of patient care.

Abstract 868: Heritable cancer mutations in multiple myeloma

Abstract Background: Epidemiologic studies have shown familial aggregations of multiple myeloma (MM) and other hematologic malignancies, but little is known about heritable genetic susceptibilities in these patients. The purpose of this study is to investigate the prevalence of known germline cancer-predisposing mutations (CPM) in patients with multiple myeloma (MM). Methods: We analyzed a set of 895 newly diagnosed MM patients from the Multiple Myeloma Research Foundation (MMRF) CoMMpass registry for whom whole-exome sequencing of germline DNA data was available. We used the clinical annotation pipeline from Sema4, a CLIA- and CAP-certified genetic testing laboratory, in a research context, to identify patients with pathogenic or likely pathogenic CPM according to ACMG variant classification guidelines, and compared their characteristics against those without CPM. Statistical significance was assessed using the Chi-Square and Fisher's Exact tests and defined as a two-sided p value &amp;lt;0.05. Results: We identified 83 germline CPM in 31 distinct genes in 79 (8.8%) of 895 patients. Homologous recombination (HR) pathway gene mutations were the most common (n = 38, 46%), with CHEK2 being the most frequently mutated gene (n = 10, 12%). Notably, the number of mismatch repair (MMR) gene defects was considerably higher (n = 6, 1:149) than the estimated prevalence in the general population. CPM carriers were significantly more likely to be diagnosed with MM before age 40 (6.3% vs 1.8%, p = 0.025) and to have a family history (FH) of MM or leukemia (16.4% vs 6.3%, p = 0.01) than those without a CPM. Likelihood of having a FH of any malignancy was also significantly higher in the CPM group (70.9% vs 54.5%, p = 0.028). Interestingly, common CHEK2 founder mutations were observed at a much higher rate in patients with a FH of MM or leukemia (8.7% vs 0.68%, p = 0.0013). Conclusions: Our results suggest that a significant proportion of patients with MM carry germline cancer-predisposing mutations, especially those diagnosed at a very young age (&amp;lt;40 years old), and those with a family history of MM or leukemia. The observation that 6 out of 895 patients with MM had pathogenic MMR variants suggests that MM may be a previously unsuspected component of Lynch syndrome. Common CHEK2 founder mutations were strikingly frequent in patients with a FH of MM, suggesting that FH modifies the penetrance of these variants in MM predisposition, as has been observed for other cancers. Citation Format: Santiago Thibaud, Aaron Etra, Ryan Subaran, Zachry Soens, Scott Newman, Rong Chen, Ajai Chari, Hearn J. Cho, Sundar Jagannath, Deepu Madduri, David T. Melnekoff, Shambavi Richard, Joshua Richter, Larysa Sanchez, Alessandro Lagana, Samir Parekh, Kenan Onel. Heritable cancer mutations in multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 868.

Experience of 34 Years of Multiple Myeloma in a Reference Center of a Developing Country

Introduction: Multiple Myeloma (MM) is characterized by a significant morbidity and mortality. Recent advances have improved knowledge of biology of MM, and incorporation of ASCT and novel treatments have transformed the natural history of MM, improving overall survival (OS). However, relatively little is known about the epidemiology and outcomes in developing countries such as Colombia.Purpose: The aim of this study was to identify the clinical and pathological features and outcomes of MM patients in a Colombian reference center.Methods: We reviewed the medical records of patients referred to Hospital Fundación Santa Fe, Colombia between January 1983 and June 2017, with previous approval by the Institutional Review Board. Newly diagnosed MM patients were retrospectively included in this study. Diagnoses were reviewed according to IMWG criteria. The records of all patients were revised; clinical information was collected and analyzed. Descriptive analysis was performed, and variables were correlated by Spearman´s coefficient. Survival analysis was performed by Kaplain Meier curves and a Cox coefficient model was performed using the variables ISS risk and transplants. Statistical association was considered for p values <0.05.Results: A total of184 newly diagnosed MM patients were included, with median age of 66.5 years old (range 23-91 years), 3.7% were younger than 50 years old. There was not a difference between gender (female: 89; male: 95 patients). Patients were classified as ISS III and ISS II in the 33% and 31% of the cases, respectively. At diagnosis, leading symptoms were bone pain (48.8%) and fatigue (20%). Also, the patients presented hypercalcemia (11%) and renal impairment (20%). The whole blood count showed hemoglobin less than 10 mg/dl in 25.5% of patients and pancytopenia in 3.8%. Only 8.3% were diagnosed previously with MGUS and 8.3% had autoimmune disease, the most frequent was rheumatoid arthritis (26.6%). 33.15% had expositional factor history (tobacco smoking 83.6%), 9.2% had history of cancer (most frequently prostate cancer). 28.5% of patients referred have a first-degree relative with cancer, being the most frequent was breast cancer (32.7%).The most frequent isotypes of immunoglobulins were IgG (59.74%), followed by IgA (25%). 16.8% were only light chain and 2.5% were non-secretory. Free light chain showed an abnormal ratio in the majority of patients (88.235%). The morphologic presence of circulating plasma cells was detected in 1.6% of patients and bone marrow aspirates showed a range of infiltration by MM between 10 to 93%. Flow Cytometry identified a median of tumor plasma cells of 15%.The most commonly aberrant antigen expression detected was CD19 (94.82%), CD45 (84.2%), CD56 (59.3%). There was a strong positive correlation between the measure of aspirate and flow cytometry (Spearman 70%; p=0.000). Only 13 patients were assessed with FISH and 3 had p53 deletion. All patients were analyzed with conventional radiography, allowing alterations identification in 77% of patients (75.2% with lytic lesions and 17% with fractures).One hundred and four patients could be followed for more than 4 months, with a mean of 39.67 months and OS of all cohort was 44.03 months. The 5-year OS rate was 80% (CI95%=57.7-91.5) in ISS I, 65% (CI95%=31.6-85.4) in ISS II, and 53% (CI95%=29.8-72) in ISS III groups (Figure 1). 39.5 % received ASCT, their OS was 74% (CI95%= 52.4-87) versus 71% transplantation-ineligible patients (CI95%= 56.3-81.7). Cox regression model showed association between mortality and ISS (HR: 1.93; 95%CI: 1.15-3.24), but no association with transplant (HR: 0.73; 95%CI: 0.31-1.71). 35% died, the main cause of death was related to infectious processes.ConclusionsThis study showed that MM patients of a reference center of a developing country have similar clinical, immunological and pathological characteristics, as well as OS, stratified according ISS, compared to published data in developed countries. However, there was fewer number of patients that received ASCT, Therefore, it is important to work for improving its access and to develop new treatments for patients in developing countries. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.