Plasmacytoma Research Articles

Daratumumab-based regimens for patients with multiple myeloma plus extramedullary plasmacytomas or paraskeletal plasmacytomas: initial follow-up of an Italian multicenter observational clinical experience.

Myeloma with extramedullary plasmacytomas not adjacent to bone (EMP) is associated with an extremely poor outcome compared with paraosseous plasmacytomas (PP) as current therapeutic approaches are unsatisfactory. The role of new molecules and in particular of monoclonal antibodies is under investigation. To determine whether daratumumab-based regimens are effective for myeloma with EMP, we report herein an initial multicenter observational analysis of 102 myeloma patients with EMP (n = 10) and PP (n = 25) at diagnosis and EMP (n = 28) and PP (n = 39) at relapse, treated with daratumumab-based regimens at 11 Haematological Centers in Italy.EMP and PP at diagnosis were associated with higher biochemical (90% vs. 96%, respectively) and instrumental ORR (86% vs. 83.3%, respectively), while at relapse, biochemical (74% vs. 73%) and instrumental (53% vs. 59%) ORR were lower. Median OS was inferior in EMP patients compared with patients with PP both at diagnosis (21.0 months vs. NR) (p = 0.005) and at relapse (32.0 vs. 40.0 months) (p = 0.428), although, during relapse, there was no statistically significant difference between the two groups. Surprisingly, at diagnosis, median TTP and median TTNT were not reached either in EMP patients or PP patients and during relapse there were no statistically significant differences in terms of median TTP (20 months for two groups), and median TTNT (24 months for PP patients vs. 22 months for EMP patients) between the two groups. Median TTR was 1 month in all populations.These promising results were documented even in the absence of local radiotherapy and in transplant-ineligible patients.

New classifications of B-cell neoplasms: a comparison of 5th WHO and International Consensus classifications.

In 2024, the World Health Organization (WHO) launched a new classification of lymphoid neoplasms, a revision of the previously used Revised 4th Edition of their classification (WHO-4R). However, this means that two classifications are now in simultaneous use: the 5th Edition of the WHO classification (WHO-5) and the International Consensus Classification (ICC). Instead of a comprehensive review of each disease entity, as already described elsewhere, this review focuses on revisions made in both the WHO-5 and ICC from WHO-4R and discrepancies between them regarding B-cell neoplasms. Similarities include cutaneous marginal zone lymphoma, cold agglutinin disease, non-primary effusion lymphoma-type effusion-based lymphoma, and gray zone lymphoma. Differences include plasma cell neoplasms, high-grade B-cell lymphoma (double hit lymphoma), follicular lymphoma, LPD with immune deficiency and dysregulation, extranodal large B-cell lymphoma, transformations of indolent B-cell lymphomas, and diffuse large B-cell lymphoma, not otherwise specified. Understanding the similarities and differences between the two latest classifications will aid daily diagnostic practice and future research on lymphoid neoplasms.

Monoclonal gammopathy in the setting of Pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis characterized by ulcerative painful lesions with violaceous undermined borders. Up to 75% of PG cases develop in association with an underlying systemic disease. Monoclonal gammopathy is reportedly a concomitant condition with PG, with studies indicating immunoglobulin (Ig) A gammopathy as the most common. Whether gammopathy is associated with PG or is an incidental finding has been debated. We sought to investigate the association and characteristics of gammopathy in patients with PG. We retrospectively identified PG patients at our institution from 2010 to 2022 who were screened for plasma cell dyscrasia. Of 106 patients identified, 29 (27%) had a gammopathy; subtypes included IgA (41%), IgG (28%), and biclonal (IgA and IgG) (14%). Mean age was similar between those with and without gammopathy (60.7 vs. 55.9 years; P = .26). In addition, hematologic or solid organ cancer developed in significantly more patients with vs. without gammopathy (8/29 [28%] vs. 5/77 [6%]; P = .003). Among the subtypes of gammopathy, IgG monoclonal gammopathy had the highest proportion of patients with subsequent cancer development (4 of 8 patients, 50%). Study limitations include a retrospective, single-institution design with a limited number of patients. Overall, our data show a high prevalence of gammopathy in patients with PG; those patients additionally had an increased incidence of cancer, especially hematologic cancer.

Multiple Myeloma Revealed by a Plasmacytoma of the Sphenoid Sinus in a Young Subject: Case Report

Extramedullary plasmacytomas are a rare entity. They represent less than 1% of malignant head and neck tumors. We report the case of a 42-year-old patient complaining of headache, ptosis of the right eye and hypoesthesia of the face evolving for a few weeks. MRI showed a mass in the sphenoid sinus with local extension. The myelogram objectified the presence of 60% dystrophic plasma cells, which confirms the diagnosis of multiple myeloma. The patient received chemotherapy with a good course. Here, we report a rare case of sphenoidal sinus plasmacytoma that evolved into multiple myeloma.

The genomic landscape of Vk*MYC myeloma highlights shared pathways of transformation between mice and humans

Multiple myeloma (MM) is a heterogeneous disease characterized by frequent MYC translocations. Sporadic MYC activation in the germinal center of genetically engineered Vk*MYC mice is sufficient to induce plasma cell tumors in which a variety of secondary mutations are spontaneously acquired and selected over time. Analysis of 119 Vk*MYC myeloma reveals recurrent copy number alterations, structural variations, chromothripsis, driver mutations, apolipoprotein B mRNA-editing enzyme, catalytic polypeptide (APOBEC) mutational activity, and a progressive decrease in immunoglobulin transcription that inversely correlates with proliferation. Moreover, we identify frequent insertional mutagenesis by endogenous retro-elements as a murine specific mechanism to activate NF-kB and IL6 signaling pathways shared with human MM. Despite the increased genomic complexity associated with progression, advanced tumors remain dependent on MYC. In summary, here we credential the Vk*MYC mouse as a unique resource to explore MM genomic evolution and describe a fully annotated collection of diverse and immortalized murine MM tumors.

CyberKnife stereotactic radiosurgery for extramedullary plasmacytoma in the external auditory canal: illustrative case.

Plasmacytoma, a rare plasma cell disorder, often presents as a solitary or multiple tumors within the bone marrow or soft tissues, typically associated with multiple myeloma. Extramedullary plasmacytomas (EMPs), particularly those located in the external auditory canal (EAC), are exceedingly rare and pose significant treatment challenges given their location, anatomical complexity, and high risk of recurrence. The authors report the case of a 72-year-old male with a history of multiple myeloma, presenting with recurrent left EAC plasmacytoma. After initial conventional radiotherapy for the lesion, a recurrence was documented in 7 years. The patient subsequently underwent stereotactic radiosurgery, which proved successful, leading to complete resolution of the lesion without any long-term adverse effects or radiation-related complications over a 45-month period. This case is a unique instance of utilizing stereotactic radiosurgery for recurrent EMP in the EAC, highlighting its potential as an effective approach in managing complex plasmacytomas.

Detection of clonal plasma cells in POEMS syndrome using multiparameter flow cytometry

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein], and skin changes) is a rare systemic disorder characterized by various symptoms caused by underlying plasma cell (PC) dyscrasia. Detection of monoclonal PCs is mandatory for the diagnosis of POEMS syndrome; however, the usefulness of EuroFlow-based next-generation flow cytometry (EuroFlow-NGF) in POEMS syndrome for detecting monoclonal PCs in bone marrow (BM) and the gating strategy suitable for flow cytometry study of POEMS syndrome remain unknown. We employed EuroFlow-NGF-based single-tube eight-color multiparameter flow cytometry (MM-flow) and established a new gating strategy (POEMS-flow) to detect the monoclonal PCs in POEMS syndrome, gating CD38 broadly from dim to bright and CD45 narrowly from negative to dim compared to MM-flow. MM-flow detected monoclonal PCs in 9/25 (36.0%) cases, including 2/2 immunofixation electrophoresis (IFE)-negative cases (100%). However, POEMS-flow detected monoclonal PCs in 18/25 cases (72.0%), including 2/2 IFE-negative cases (100%). POEMS-flow detected monoclonal PCs with immunophenotypes of CD19− in 17/18 (94.4%). In six cases where post-treatment samples were available, the size of the clones was significantly reduced after the treatment (P = 0.031). POEMS-flow can enhance the identification rate of monoclonal PCs in POEMS syndrome and become a valuable tool for the diagnosis of POEMS syndrome.

Starry Sky Appearance of an Amyloid Heart in Plasma Cell Dyscrasias

We report an extremely rare case of amyloid heart with classical “Starry Sky” appearance in echocardiography in a 52-year-old male presenting with systemic amyloidosis secondary to plasma cell dyscrasias. Interestingly, patient presented with diffuse myalgia unresponsive to traditional nonsteroidal anti-inflammatory drugs with effort dyspnea New York Heart Association Class II secondary to Grade II diastolic dysfunction of stiff myocardium infiltrated with amyloid protein. A starry sky pattern of an amyloid heart led to the retrospective diagnosis of plasma cell dyscrasias with presence of 30% plasma cells in bone marrow biopsy without the presence of M band in serum electrophoresis.

Long-term survival for lymphoid neoplasms and national health expenditure (EUROCARE-6): a retrospective, population-based study

Management of lymphoid malignancies requires substantial health system resources. Total national health expenditure might influence population-based lymphoid malignancy survival. We studied the long-term survival of patients with 12 lymphoid malignancy types and examined whether different levels of national health expenditure might explain differences in lymphoid malignancy prognosis between European countries and regions. For this observational, retrospective, population-based study, we analysed the EUROCARE-6 dataset of patients aged 15 or older diagnosed between 2001 and 2013 with one of 12 lymphoid malignancies defined according to International Classification of Disease for Oncology (third edition) and WHO classification, and followed up to 2014 (Jan 1, 2001-Dec 31, 2014). Countries were classified according to their mean total national health expenditure quartile in 2001-13. For each lymphoid malignancy, 5-year and 10-year age-standardised relative survival (ASRS) was calculated using the period approach. Generalised linear models indicated the effects of age at diagnosis, gender, and total national health expenditure on the relative excess risk of death (RER). 82 cancer registries (61 regional and 21 national) from 27 European countries provided data eligible for 10-year survival estimates comprising 890 730 lymphoid malignancy cases diagnosed in 2001-13. Median follow-up time was 13 years (IQR 13-14). Of the 12 lymphoid malignancies, the 10-year ASRS in Europe was highest for hairy cell leukaemia (82·6% [95% CI 78·9-86·5) and Hodgkin lymphoma (79·3% [78·6-79·9]) and lowest for plasma cell neoplasms (29·5% [28·9-30·0]). RER increased with age at diagnosis, particularly from 55-64 years to 75 years or older, for all lymphoid malignancies. Women had higher ASRS than men for all lymphoid malignancies, except for precursor B, T, or natural killer cell, or not-otherwise specified lymphoblastic lymphoma or leukaemia. 10-year ASRS for each lymphoid malignancy was higher (and the RER lower) in countries in the highest national health expenditure quartile than in countries in the lowest quartile, with a decreasing pattern through quartiles for many lymphoid malignancies. 10-year ASRS for non-Hodgkin lymphoma, the most representative class for lymphoid malignancies based on the number of incident cases, was 59·3% (95% CI 58·7-60·0) in the first quartile, 57·6% (55·2-58·7) in the second quartile, 55·4% (54·3-56·5) in the third quartile, and 44·7% (43·6-45·8) in the fourth quartile; with reference to the European mean, the RER was 0·80 (95% CI 0·79-0·82) in the first, 0·91 (0·90-0·93) in the second, 0·94 (0·92-0·96) in the third, and 1·45 (1·42-1·48) in the fourth quartiles. Total national health expenditure is associated with geographical inequalities in lymphoid malignancy prognosis. Policy decisions on allocating economic resources and implementing evidence-based models of care are needed to reduce these differences. Italian Ministry of Health, European Commission, Estonian Research Council.

A young patient with cord compression diagnosed as a solitary sacral plasmacytoma: a case report

Plasmacytoma is a subgroup of plasma cell neoplasms characterized by localized proliferation of neoplastic plasma cells. It is a rare disease that accounts for only less than 5% of all plasma cell tumours and can present alone or with multiple myeloma. Here, we report a clinical case of unusual presentation, in which solitary sacral plasmacytoma of a previously well young woman presented with bilateral lower limb numbness. She was found to have a sacral-originated tumour, which was later diagnosed as a solitary sacral plasmacytoma with the help of imaging and histological evaluation, along with the absence of the end organ damage.

Patient perspectives on BCMA-targeted therapies for multiple myeloma: a survey conducted in a patient advocacy group.

Advances in multiple myeloma (MM) treatment have shifted the therapeutic landscape. Understanding patients' perspectives can assist physicians in helping patients make informed decisions. This study aimed to understand the patient decision-making process and gain insights into patient perspectives on B-cell maturation antigen (BCMA)-targeted therapies for MM. An 18-question survey was completed by patients with MM enrolled in HealthTree® Cure Hub, an online portal helping patients with plasma cell dyscrasias navigate their disease. From October 28, 2022, to January 12, 2023, 325 patients with MM participated in the survey. The mean age (standard deviation) of the respondents was 66 (8) years; 54% were female and 90% were White. Among 218 patients with complete clinical records in the database, the median (min, max) lines of therapy (LOT) was 2 (1,16). Among 61 (28%) patients who had received ≥4 LOTs, 55 (90%) were triple-class exposed. Of the 290 patients who responded to the question about openness to new therapies, 76 (26%) were open to trying a new therapy immediately and 125 (43%) wanted more information on safety and efficacy. Most respondents reported likely or very likely to try a BCMA CAR T-cell therapy (60%) or a bispecific antibody (74%) and some needed more information to decide (16% for CAR T-cell therapy and 13% for bispecific antibody). The most requested information included efficacy, side effects (SEs), eligibility, and administration process for both CAR T-cell and bispecific therapies. When 2 therapies with the same efficacy and duration of response were offered, 69% of respondents would prefer the therapy with a lower risk of severe SEs but requires continuous dosing with no treatment-free interval, and 31% preferred a therapy given once followed by a treatment-free interval but with a potentially higher risk of severe SEs. To receive an effective therapy, the top acceptable trade-offs included frequent monitoring of SEs and initiating a new therapy in a hospital setting, and the least acceptable compromise was caregiver burden. This study found a high level of openness in patients with MM to try BCMA-targeted therapies. Information on efficacy, safety, availability, and eligibility may assist patients on decision-making.

Immune escape of multiple myeloma cells results from low miR29b and the ensuing epigenetic silencing of proteasome genes

BackgroundActivation of CD28 on multiple myeloma (MM) plasma cells, by binding to CD80 and CD86 on dendritic cells, decreases proteasome subunit expression in the tumor cells and thereby helps them evade being killed by CD8+ T cells. Understanding how CD28 activation leads to proteasome subunit downregulation is needed to design new MM therapies.MethodsThis study investigates the molecular pathway downstream of CD28 activation, using an in vitro model consisting of myeloma cell lines stimulated with anti-CD28-coated beads.ResultsWe show that CD28 engagement on U266 and RPMI 8226 cells activates the PI3K/AKT pathway, reduces miR29b expression, increases the expression of DNA methyltransferase 3B (DNMT3B, a target of miR29b), and decreases immunoproteasome subunit expression. In vitro transfection of U266 and RPMI 8226 cells with a miR29b mimic downregulates the PI3K/AKT pathway and DNMT3B expression, restores proteasome subunit levels, and promotes myeloma cell killing by bone marrow CD8+ T cells from MM patients. Freshly purified bone marrow plasma cells (CD138+) from MM patients have lower miR29b and higher DNMT3B (mRNA and protein) than do cells from patients with monoclonal gammopathy of undetermined significance. Finally, in MM patients, high DNMT3B levels associate with shorter overall survival.ConclusionsAltogether, this study describes a novel molecular pathway in MM. This pathway starts from CD28 expressed on tumor plasma cells and, through the PI3K-miR29b-DNMT3B axis, leads to epigenetic silencing of immunoproteasome subunits, allowing MM plasma cells to elude immunosurveillance. This discovery has implications for the design of innovative miR29b-based therapies for MM.

Construction of immune-related gene pairs signature to predict the overall survival of multiple myeloma patients based on whole bone marrow gene expression profiling.

Multiple myeloma (MM) is a plasma cell dyscrasia that is characterized by the uncontrolled proliferation of malignant PCs in the bone marrow. Due to immunotherapy, attention has returned to the immune system in MM, and it appears necessary to identify biomarkers in this area. In this study, we created a prognostic model for MM using immune-related gene pairs (IRGPs), with the advantage that it is not affected by technical bias. After retrieving microarray data of MM patients, bioinformatics analyses like COX regression and least absolute shrinkage and selection operator (LASSO) were used to construct the signature. Then its prognostic value is assessed via time-dependent receiver operating characteristic (ROC) and the Kaplan-Meier (KM) analysis. We also used XCELL to examine the status of immune cell infiltration among MM patients. 6-IRGP signatures were developed and proved to predict MM prognosis with a P-value of 0.001 in the KM analysis. Moreover, the risk score was significantly associated with clinicopathological characteristics and was an independent prognostic factor. Of note, the combination of age and β2-microglobulin with risk score could improve the accuracy of determining patients' prognosis with the values of the area under the curve (AUC) of 0.73 in 5 years ROC curves. Our model was also associated with the distribution of immune cells. This novel signature, either alone or in combination with age and β2-microglobulin, showed a good prognostic predictive value and might be used to guide the management of MM patients in clinical practice.

Melan-A immunolabeling in canine extramedullary plasmacytomas.

Histologic diagnosis of less well-differentiated cases of canine extramedullary plasmacytomas (CEMPs) may require immunohistochemical confirmation to discriminate these tumors from other round cells tumors including lymphoma, cutaneous histiocytoma, and amelanotic melanomas. CEMPs are characterized by widespread immunoreactivity for multiple myeloma 1 (MUM1) antigen and λ light chains, while the melanocytic marker melan-A has been reported to yield negative results. Here, 33 randomly selected CEMPs, 20 melanocytomas, and 20 malignant melanomas were immunohistochemically tested for MUM1, melan-A, and PNL2. In addition, CEMPs were examined for PAX5, E-cadherin, CD3, CD18, CD20, S100, as well as λ and κ light chain immunoreactivity. All CEMPs were characterized by labeling for MUM1 and λ light chain, as well as variable immunopositivity for the remaining antibodies. Notably, 13 cases of CEMPs (39.4%) exhibited immunolabeling for melan-A. Melanocytic tumors immunolabeled for melan-A (40/40; 100%) and PNL2 (34/40; 85%). An unexpected cytoplasmic immunoreactivity for MUM1 was observed in 2 melanocytic tumors. Summarized, MUM1 or melan-A immunomarkers alone are not sufficient to differentiate between CEMPs and amelanotic melanomas and should be part of a larger immunopanel including λ light chain, CD20, and PNL2.

Serological Response to COVID-19 Vaccination is Impaired in Adults with Hematologic Malignancies when Compared to Adults with Solid Tumors and HIV: Observations from a Single Tertiary Institution

Background: Hematologic malignancies can impair immune responses following COVID-19 vaccination. We analyzed seroconversion rates following a primary two-dose COVID-19 vaccination series and subsequent seroconversion rates after booster doses (doses 3 and above) in patients with various subtypes of hematologic malignancies (HM), human immunodeficiency virus infection (HIV), and solid tumors (ST). Methods: We conducted a retrospective study of 299 fully vaccinated adults with HM (n=202), HIV without diagnosed cancer (n=48), HIV and cancer (n=17), ST (n=12), autoimmune diseases (n=12), or other hematologic diseases (n=10) seen in a single tertiary institution between May 2020 and July 2022. A serum spike antibody level ≥0.8U/mL was considered evidence of seroconversion as defined by the manufacturer (Roche Elecsys®). A Mann-Whitney test was utilized to analyze continuous variables and a chi-square test for categorical variables. Results: Seroconversion after initial vaccination was significantly associated with disease category and treatment. Seroconversion rates were lowest in people with B-cell lymphomas (including patients not currently receiving treatment) (44/68) and patients receiving anti-B-cell monoclonal antibodies (23/57). All individuals with HIV alone or ST (n=60) demonstrated seroconversion after initial vaccination as did 94% of individuals with HIV and cancer (16/17) and 86% of those with plasma cell dyscrasias (37/43). Of the 51 people who did not seroconvert after their primary vaccination course, 25 achieved seroconversions after one booster dose. Conclusion: Our study supports the potential utility of COVID-19 serological testing to identify those at high risk of impaired response to COVID-19 vaccination and to help physicians develop personalized vaccination strategies. Continued research is needed to refine our understanding of immune response in these patients and improve their protection against COVID-19. Keywords: COVID-19 Vaccination, Impaired Immune Response, Seroconversion, HIV, Hematologic Malignancies

Development and validation of a machine learning-based postoperative prognostic model for plasma cell neoplasia with spinal lesions as initial clinical manifestations: a single-center cohort study.

Spinal multiple myeloma (MM) and solitary plasmacytoma of bone (SPB), both plasma cell neoplasms, greatly affect patients' quality of life due to spinal involvement. Accurate prediction of surgical outcomes is crucial for personalized patient care, but systematic treatment guidelines and predictive models are lacking. This study aimed to develop and validate a machine learning (ML)-based model to predict postoperative outcomes and identify prognostic factors for patients with spinal MM and SPB. A retrospective analysis was conducted on patients diagnosed with MM or SPB from 2011 to 2015, followed by prospective data collection from 2016 to 2017. Patient demographics, tumor characteristics, clinical treatments, and laboratory results were analyzed as input features. Four types of ML algorithms were employed for model development. The performance was assessed using discrimination and calibration measures, and the Shapley Additive exPlanations (SHAP) method was applied for model interpretation. A total of 169 patients were included, with 119 for model training and 50 for validation. The Gaussian Naïve Bayes (GNB) model exhibited superior predictive accuracy and stability. Prospective validation on the 50 patients revealed an area under the curve (AUC) of 0.863, effectively distinguishing between 5-year survivors and non-survivors. Key prognostic factors identified included International Staging System (ISS) stage, Durie-Salmon (DS) stage, targeted therapy, and age. The GNB model has the best performance and high reliability in predicting postoperative outcomes. Variables such as ISS stage and DS stage were significant in influencing patient prognosis. This study enhances the ability to identify patients at risk of poor outcomes, thereby aiding clinical decision-making.

PLASMA CELL LEUKEMIA: AN AGGRESSIVE DISEASE, A CAUSE OF DIAGNOSTIC ERROR

Plasma cell leukemia (LP) is a rare and aggressive plasma cell tumor that manifests as significant clonal expansion of plasma cells in the bone marrow and peripheral blood. It is considered primary when it presents at initial diagnosis and secondary when it occurs in patients with pre-existing multiple myeloma (MM). Because of the high frequency of extramedullary injuries, plasma cell leukemia is a major source of diagnostic error that can lead to fatality. We report a case of plasma cell leukemia diagnosed at the clinical haematology department of the CNTS in Dakar (Senegal).

Non-invasive prenatal test identifies circulating cell-free DNA chromosomal abnormalities derived from clonal hematopoiesis in aggressive hematological malignancies

Liquid biopsy is a minimally invasive diagnostic tool for identification of tumor-related mutations in circulating cell-free DNA (cfDNA). The aim of this study was to investigate feasibility, sensitivity, and specificity of non-invasive prenatal test (NIPT) for identification of chromosomal abnormalities in cfDNA from a total of 77 consecutive patients with non-Hodgkin B-cell lymphomas, Hodgkin lymphoma (HL), or plasma cell dyscrasia. In this case series, half of patients had at least one alteration, more frequently in chromosome 6 (23.1%), chromosome 9 (20.5%), and chromosomes 3 and 18 (16.7%), with losses of chromosome 6 and gains of chromosome 7 negatively impacting on overall survival (OS), with a 5-year OS of 26.9% and a median OS of 14.6 months, respectively (P = 0.0009 and P = 0.0004). Moreover, B-cell lymphomas had the highest NIPT positivity, especially those with aggressive lymphomas, while patients with plasma cell dyscrasia with extramedullary disease had a higher NIPT positivity compared to conventional cytogenetics analysis and a worse outcome. Therefore, we proposed a NIPT-based liquid biopsy a complementary minimally invasive tool for chromosomal abnormality detection in hematological malignancies. However, prospective studies on larger cohorts are needed to validate clinical utility of NIPT-based liquid biopsy in routinely clinical practice.

Abstract CT001: Linvoseltamab, a B-cell maturation antigen-targeted T-cell-engaging bispecific antibody, induces deep and durable responses in patients with relapsed or refractory multiple myeloma including difficult-to-treat subgroups

Abstract Background We report pivotal results from the registrational filing data cut-off (DCO) of the 200 mg dose used in the LINKER-MM1 (NCT03761108) clinical trial, testing the safety and efficacy of linvoseltamab (a B-cell maturation antigen × CD3 antibody [Ab]) as treatment for relapsed/refractory multiple myeloma (RRMM). Methods Eligible patients had RRMM that either progressed on/after ≥3 lines of therapy that included a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 Ab or that was ≥double- (Phase 1) or triple- (Phase 2) class (PI/IMiD/anti-CD38 Ab) refractory. Phase 2 patients received intravenous linvoseltamab once a week through week 14, then once every 2 weeks (Q2W). Phase 2 patients achieving ≥very good partial response (VGPR) who have received treatment for ≥24 weeks transitioned to Q4W dosing. Primary endpoint was objective response rate (ORR) per Independent Review Committee (IRC). Secondary endpoints included duration of response (DOR), progression free survival (PFS), overall survival (OS), and safety. Results At DCO of Sep 8, 2023, median duration of follow-up for the 117 patients enrolled into the 200 mg dosing cohorts (phase 1+2) was 11.1 months (interquartile range 2.9-14.1). Median age was 70 years (26% ≥75), 17% were African American, 18% had International Staging System (ISS) stage III disease, 16% had extramedullary (excluding paramedullary) plasmacytomas (EMPs) ≥2 cm, 39% had high-risk cytogenetics, and 82% were ≥triple-class refractory. Linvoseltamab induced high rates of deep responses with an ORR of 71% including ≥complete response (CR) rate of 46%. Among all patients with ≥CR, 39% were documented minimal residual disease negative. These frequent and deep responses were observed across prespecified high-risk subgroups including patients with ISS stage III (ORR 62%; ≥CR 43%), and EMPs (ORR 53%; ≥CR 26%). Kaplan-Meier (KM) estimated median DOR was not reached (NR); estimated probability of ongoing response at 12 months was 78% (95% confidence interval [CI] 65-86). KM estimated PFS and OS were NR; and probability of PFS and OS at 12 months were 69% (95% CI 58-77) and 75% (65-82), respectively. The most common treatment emergent adverse event (TEAE) was cytokine release syndrome (CRS; any grade [Gr] 46%, Gr2 10%, Gr3 1%, Gr≥4 0%), which occurred mostly during step-up dosing of linvoseltamab with a median time to onset of 11 hours. Other common TEAEs were neutropenia (any Gr 41%, Gr 3-4 40%), anemia (39%, 31%), cough (36%, 0%), and diarrhea (35%, 2%). Infections occurred in 73% (Gr 3-4 34%) of patients. The frequency and severity of infections decreased after 6 months coincident with Q4W dosing. Conclusions Linvoseltamab induced high rates of deep and durable responses in patients with RRMM including those in high-risk subgroups. Linvoseltamab is associated with a generally predictable timing of CRS, and the Q4W response adapted schedule in patients with ≥VGPR may provide a substantial benefit for patient convenience and is associated with a reduced infection rate. Citation Format: Sundar Jagannath, Joshua Richter, Madhav V. Dhodapkar, James E. Hoffman, Hans C. Lee, Attaya Suvannasankha, Mansi R. Shah, Suzanne Lentzsch, Jeffrey A. Zonder, Rachid Baz, Joseph J. Maly, Swathi Namburi, Ka Lung Wu, Matthew Pianko, Rebecca Silbermann, Chang-Ki Min, Marie-Christiane Vekemans, Markus Munder, Ja Min Byun, Joaquín Martínez Lopez, Michelle DeVeaux, Dhruti Chokshi, Anita Boyapati, Anasuya Hazra, Karen Rodriguez Lorenc, Glenn S. Kroog, Yariv Houvras, Naresh Bumma. Linvoseltamab, a B-cell maturation antigen-targeted T-cell-engaging bispecific antibody, induces deep and durable responses in patients with relapsed or refractory multiple myeloma including difficult-to-treat subgroups [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT001.

Nasal cavity extramedullary plasmacytoma: literature review and clinical experience

Abstract BACKGROUND. Extramedullary plasmacytoma is an extremely rare solitary plasma cell neoplasm that occurs in locations other than bone, without involving the bone marrow. It is commonly located in the upper aerodigestive tract. In the head and neck region, the most frequent location is the sinonasal region. MATERIAL AND METHODS. A systemic review in accordance with the PRISMA guidelines was done with research works in PubMed, Elsevier database, Cochrane library, Web of Science, Scopus, Crossref and Google Scholar. The search was carried out using the keywords “plasmacytoma and nose”, “extramedullary plasmacytoma”, “extramedullary plasmacytoma of nose”, “plasmacytoma and nasal cavity”, and “extramedullary plasmacytoma of nasal cavity”. RESULTS. We analysed 27 research works with a total number of 32 cases. The most common presenting symptoms were nasal cavity bleeding. The disease showed a male preponderance (78.1%). Bone erosion was seen in 7 cases. The histopathological examination showed plasma cells arranged predominantly as a uniform population or sheet-like appearance. A common immunohistochemical marker was CD138 (11 cases). Treatment was primarily radiotherapy (43.7%). We are also reporting a case of a 53-year-old male with plasmacytoma of the middle turbinate managed by wide resection and postoperative radiotherapy. CONCLUSION. Though a less common condition, in a case of polypoidal-like lesion with bleeding tendency, the clinician should keep in mind the possibility of extramedullary plasmacytoma. The diagnosis is made with histopathological examination and immunohisto-chemistry of the tissue involved. Treatment can be radiotherapy, surgery, or a combination of modalities.