Úvod a cíl: Předkládaná kazuistika dokumentuje průběh diagnostiky a léčby neoplazie plazmatických buněk dolní čelisti 79leté pacientky. Cílem je upozornit na možnost manifestace plazmocytomů v diferenciální diagnostice lézí čelistních kostí a zároveň zdůraznit důležitost mezioborové spolupráce, v tomto případě dentoalveolárního/maxilofaciálního chirurga a hematoonkologa. Popis případu: Pacientka byla na našem pracovišti poprvé vyšetřena v listopadu 2023 na žádost praktického zubního lékaře z důvodu opakujících se obtíží po extrakci stálého dolního druhého moláru vpravo (zub č. 47), která byla provedena o dva měsíce dříve. Pacientka byla v roce 2021 operována pro karcinom vaječníků, netrpěla diabetem, krvácivými projevy, dušností ani jinými chorobami. Neužívala léky ovlivňující kostní metabolismus. Na základě klinického obrazu, délky trvání příznaků, OPG zobrazujícího neostře ohraničené projasnění těla mandibuly v oblasti chybějících zubů a laboratorního vyšetření byla stanovena pracovní diagnóza osteomyelitida těla dolní čelisti vpravo. Neprodleně byla zahájena empirická léčba perorálními širokospektrými antibiotiky penicilinové řady, která přinesla klinické zlepšení. CBCT zhotovené dva dny po prvním vyšetření odhalilo nejasně ohraničené osteolytické ložisko způsobující resorpci lingvální stěny těla mandibuly dosahující spodní hrany dolní čelisti v oblasti molárů vpravo dole. Tento rentgenologický nález vedl k podezření na zhoubný novotvar dolní čelisti. Následné vyšetření pomocí CT s kontrastní látkou potvrdilo infiltraci měkkých tkání a výše popsaný charakter osteolytické léze. Na základě těchto nálezů byla indikována a provedena diagnostická biopsie části patologické tkáně, která odhalila plazmocytární neoplazii. V diferenciální diagnostice bylo nutné rozlišit, zda se jedná o solitární kostní plazmocytom s extraoseální propagací, nebo infiltraci mnohočetným myelomem. Pacientka byla odeslána na hematologické vyšetření na specializované pracoviště, kde byla definitivně stanovena diagnóza mnohočetného myelomu. Zde byla pacientka léčena trojkombinací bortezomidu, lenalidomidu a dexametazonu. Již první cyklus této léčby vedl k úplné regresi intraorální léze a zhojení extrakční rány v místě zubu 47. Závěr: Tato kazuistika upozorňuje na méně častý, avšak možný výskyt plazmocytomů v dutině ústní a zdůrazňuje důležitost mezioborové spolupráce.

Introduction and aim: The presented case study documents the course of diagnosis and treatment of plasma cell neoplasia of the lower jaw in a 79-years-old female patient. The aim is to highlight the possibility of plasmacytoma manifestation in the differential diagnosis of jawbone lesions and to emphasize the importance of interdisciplinary cooperation, in this case between the dentoalveolar/maxillofacial surgeon and the haematooncologist. Case description: The patient was first examined at our facility in November 2023 upon the request of a general dental practitioner due to recurrent difficulties following extraction of the right permanent lower second molar (tooth #47), which had been performed two months earlier. In 2021, the patient underwent surgery for ovarian carcinoma and had no history of diabetes, bleeding disorders, shortness of breath, or other illnesses. She was not using any medications affecting bone metabolism. Based on the clinical findings, duration of symptoms, OPG image showing noticeable poorly defined radiolucency of the mandibular body in the area of missing teeth, and laboratory tests, a working diagnosis of osteomyelitis of the mandibular body on the right side was established. Empirical treatment with oral broad-spectrum antibiotics of the penicillin class was initiated promptly and resulted in clinical improvement. Cone-beam computed tomography (CBCT) performed two days after the initial examination revealed osteolytic indistinctly demarcated changes causing lingual wall resorption of the mandibular body reaching to the lower edge of the mandible in the region of the molars on the lower right side. This radiological finding raised suspicion of malignant neoplasm of the lower jaw. Subsequent CT scan with contrast confirmed soft tissue infiltration and the osteolytic nature of the lesion described above. Based on these findings, a diagnostic biopsy of the pathological tissue was indicated and performed, revealing plasma cell neoplasia. In the differential diagnosis, it was necessary to distinguish whether it was a solitary bone plasmacytoma with extraosseous propagation or multiple myeloma infiltration. The patient was referred for haematological examination to a specialized clinic where a definitive diagnosis of multiple myeloma was established. There the patient was treated with a triple combination of bortezomide, lenalidomide, and dexamethasone. The first cycle of this treatment resulted in complete regression of the intraoral lesion and healing of the extraction socket at the site of tooth #47. Conclusion: This case study highlights the rare but possible occurrence of oral plasmacytomas and emphasizes the importance of interdisciplinary collaboration.

• MeSH
• Bortezomib therapeutic use   MeSH
• Dexamethasone therapeutic use   MeSH
• Diagnosis, Differential MeSH
• Tooth Extraction MeSH
• Immunologic Factors MeSH
• Lenalidomide therapeutic use   MeSH
• Humans MeSH
• Interdisciplinary Communication MeSH
• Multiple Myeloma diagnosis   drug therapy   MeSH
• Mandibular Neoplasms * diagnosis   drug therapy   MeSH
• Plasmacytoma diagnosis   drug therapy   MeSH
• Dry Socket diagnostic imaging   drug therapy   MeSH
• Antineoplastic Agents MeSH
• Antineoplastic Combined Chemotherapy Protocols MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Shoulder Pain diagnosis   MeSH
• Diagnostic Errors legislation & jurisprudence   MeSH
• Humans MeSH
• Plasmacytoma diagnosis   MeSH
• Peer Review, Health Care * MeSH
• General Practice MeSH
• Expert Testimony MeSH
• Check Tag
• Humans MeSH

WHO klasifikace krevních nemocí řadí do skupiny označené termínem plazmocelulární malignity mnohočetný myelom, solitární plazmocytom a plazmocelulární leukemii. Pro stanovení diagnózy symptomatického mnohočetného myelomu je požadován průkaz ≥10% klonálních plazmocytů v kostní dřeni nebo histologický průkaz plazmocytomu plus průkaz jednoho či více symptomů mnohočetného myelomu ze skupiny CRAB (hyperkalcemie, renální insuficience, anémie nebo osteolytická ložiska), případně dalších znaků charakterizujících aktivní myelom (plazmocytóza kostní dřeně ≥60%, poměr sérového involved/uninvolved volného lehkého řetězce (FLC) ≥100 (za předpokladu, že involved FLC je ≥100mg/l), nebo >1 fokální ložisko na magnetické rezonanci. Přítomnost cytogenetických změn typu del(17p), t(4;14), t(14;16), t(14;20), gain 1q, nebo p53 mutace je považována za high-risk myelom. Přítomnost jakýchkoliv dvou high risk faktorů je někdy nazývána double-hit myelom; tři a více rizikových faktorů poté triple-hit myelom. V budoucnu budou zřejmě tyto prognostické znaky důležité pro volbu terapie. V roce 2022 pouze některá pracoviště (například Mayo Clinic) rozdělují pacienty dle těchto cytogenetických znaků do prognostických skupin a modifikují terapii (viz www.msmart.org). Solitární plazmocytom je vzácná forma plazmocelulární dyskrazie, která tvoří jednu masu monoklonálních plazmocytů lokalizovanou buď extramedulárně či intraoseálně. Pacienti, u nichž aspirace kostní dřeně detekuje malé zmnožení klonální plazmocytů, kteří ale nenaplňující ani zdaleka kritéria mnohočetného myelomu, mají vyšší riziko časné progrese do symptomatického myelomu. Před léčbou je vhodné provést pozitronovou emisní tomografii anebo CT či MR zobrazení celého těla, aby nebyla přehlédnuta další ložiska. Již několik desetiletí je léčba založena na kurativní radioterapii, ale je taktéž zkoumán potenciální přínos systémové terapie pro rizikové pacienty, protože radioterapie u solitárních plazmocytů o průměru nad 5cm často selhává. Primární plazmocelulární leukemie (PCL) má nepříznivou prognózu i v době příchodu nových léků. PCL vyžaduje časnou detekci a zahájení nejúčinnější léčby. Kritéria této nemoci se změnila, starší kritéria vyžadovala ≥20% plazmocytů v periferní krvi. Současná kritéria, zveřejněná koncem roku 2021, považují za dostačující průkaz ≥5% plazmocytů v periferní krvi u pacientů, kteří jinak splňují kritéria myelomu. Přítomnost ≥5% cirkulujících plazmocytů v periferní krvi u pacientů s mnohočetným myelom je prognóza stejně nepříznivá jako při přítomnosti ≥20% plazmocytů v periferní krvi. Proto nově skupina International Myeloma Working Group definuje PCL přítomností 5% či více cirkulujících plazmatických buněk detekovatelných při cytologickém hodnocení nátěru periferní krve u pacientů s mnohočetným myelomem. V textu jsou probrány příznaky, diagnostická kritéria a léčba těchto tří chorob spadajících pod skupinové označení plazmocelulární malignity.

According the WHO classification of malignant hematologic diseases the group plasma cell neoplasms consists of multiple myeloma, solitary plasmocytoma and plasmocytic leukemia. Diagnosis of multiple myeloma requires ≥10% clonal bone marrow plasma cells or a biopsy proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE) namely CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) features felt related to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥100 (provided involved FLC is ≥100 mg/L), or >1 focal lesion on magnetic resonance imaging (MRI). The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation is considered high-risk multiple myeloma. Presence of any two high risk factors is considered double-hit myeloma; three or more high risk factors is triple-hit myeloma. Solitary plasmacytoma is an infrequent form of plasma cell dyscrasia that presents as a single mass of monoclonal plasma cells, located either extramedullary or intraosseous. In some patients, a bone marrow aspiration can detect a low monoclonal plasma cell infiltration which indicates a high risk of early progression to an overt myeloma disease. Before treatment initiation, whole body positron emission tomography-computed tomography or magnetic resonance imaging should be performed to exclude the presence of additional malignant lesions. For decades, treatment has been based on radiation, but studies exploring the potential benefit of systemic therapies for high-risk patients are urgently needed, becouse in solitary plasmocytomas of diameter more the 5 cm is the response to radioterapie often incomplete. Primary plasma cell leukemia (PCL) has a consistently ominous prognosis, even after progress in the last decades. PCL deserves a prompt identification to start the most effective treatment for this ultra-high-risk disease. The aim of this position paper is to revisit the diagnosis of PCL according to the presence of circulating plasma cells in patients otherwise meeting diagnostic criteria of multiple myeloma. The presence of ≥5% circulating plasma cells in patients with MM had a similar adverse prognostic impact as the previously defined PCL by more the 20% ciculating plasma cells. Therefore PCL is defined by International Myeloma Working Group by the presence of 5% or more circulating plasma cells in peripheral blood smears in patients otherwise diagnosed with symptomatic multiple myeloma. Diagnostic procedures and critarias are discusse in this paper and even therapy of this diesease overviewed.

• Keywords
• daratumumab,
• MeSH
• Antibodies, Monoclonal, Humanized therapeutic use   MeSH
• Immunomodulating Agents therapeutic use   MeSH
• Humans MeSH
• Multiple Myeloma diagnosis   therapy   MeSH
• Leukemia, Plasma Cell * diagnosis   therapy   MeSH
• Plasmacytoma diagnosis   therapy   MeSH
• Antineoplastic Agents therapeutic use   MeSH
• Risk Factors MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

The Phase 3 ICARIA-MM (NCT02990338) and IKEMA (NCT03275285) studies demonstrated that isatuximab (Isa) plus pomalidomide (P) and dexamethasone (d; Isa-Pd) or carfilzomib (K) and d (Isa-Kd) improved progression-free survival (PFS) versus Pd or Kd in patients with relapsed and/or refractory multiple myeloma. In this post hoc analysis of patients with soft-tissue plasmacytomas, we evaluated Isa-Pd/Isa-Kd efficacy using central radiology and central laboratory assessments. Given the low incidence of soft-tissue plasmacytomas (7.8 %, ICARIA-MM; 6.3 %, IKEMA), efficacy data were pooled across the two studies. PFS (HR, 0.47; 95 % CI, 0.21-1.08), overall response rate (50.0 % vs 17.7 %), and very good partial response or better rate (26.9 % vs 11.8 %) were improved with Isa-Pd/Isa-Kd versus Pd/Kd, with consistent improvements within individual studies. Patients with soft-tissue plasmacytomas who received Isa-Pd/Isa-Kd had similar median PFS compared with those without soft-tissue plasmacytomas and received Pd/Kd. Safety is reported individually per study. Longer median treatment duration and more Grade ≥ 3 treatment-emergent adverse events occurred in the Isa versus control arms in ICARIA-MM (36.9 vs 8.4 weeks; 85.7 % vs 70.0 %) and IKEMA (41.9 vs 29.9 weeks; 100.0 % vs 57.1 %); however, Isa did not increase the percentage of patients with fatal events or drug discontinuation. Isa-Pd or Isa-Kd is a potential new treatment option and partially overcomes the poor prognosis associated with soft-tissue plasmacytomas in relapsed and/or refractory multiple myeloma.

• MeSH
• Dexamethasone therapeutic use   MeSH
• Clinical Trials, Phase III as Topic MeSH
• Humans MeSH
• Multiple Myeloma * drug therapy   MeSH
• Neoplasms, Plasma Cell * drug therapy   MeSH
• Plasmacytoma * drug therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Humans MeSH
• Multiple Myeloma * diagnosis   physiopathology   therapy   MeSH
• Leukemia, Plasma Cell * diagnosis   physiopathology   therapy   MeSH
• Plasmacytoma * diagnosis   physiopathology   therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Je popisován vzácný případ indolentní plazmocelulární proliferace s mnohočetným postižením uzlin a přítomností monoklonální gamapatie, jeho klinický průběh, diagnostika a terapie. Zprvu byl stav hodnocen jako plazmocelulární neoplázie s postižením lymfatických uzlin, ale bez průkazu signifikantní nádorové infiltrace kostní dřeně. Dle opakovaného vyšetření kostní dřeně a lymfatických uzlin se jedná spíše o indolentní B-lymfom marginální zóny s výraznou plazmocelulární diferenciací než o extramedulární plazmocytom s postižením uzlin.

We describe the clinical course, diagnosis and therapy of a rare case of indolent plasma cell proliferation with multiple involvement of lymph nodes and monoclonal gammopathy. At first, a diagnosis of plasma cell neoplasm with generalised lymphadenopathy and without significant bone marrow infiltration was considered. However, repeated examination of the lymph nodes and bone marrow changed the diagnosis to indolent marginal zone B-cell lymphoma with plasmacytic differentiation was rather than extramedullary nodal plasmacytoma.

• Keywords
• indolentní lymfom s plazmocelulární diferenciací,
• MeSH
• Clinical Laboratory Techniques methods   MeSH
• Humans MeSH
• Lymph Nodes pathology   MeSH
• Lymphoma * diagnosis   therapy   MeSH
• Melphalan therapeutic use   MeSH
• Positron Emission Tomography Computed Tomography methods   MeSH
• Plasmacytoma * diagnosis   therapy   MeSH
• Antineoplastic Protocols MeSH
• Flow Cytometry methods   MeSH
• Aged MeSH
• Bone Marrow Transplantation methods   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Case Reports MeSH

In this review, two types of soft-tissue involvement in multiple myeloma are defined: (i) extramedullary (EMD) with haematogenous spread involving only soft tissues and (ii) paraskeletal (PS) with tumour masses arising from skeletal lesions. The incidence of EMD and PS plasmacytomas at diagnosis ranges from 1·7% to 4·5% and 7% to 34·4% respectively. EMD disease is often associated with high-risk cytogenetics, resistance to therapy and worse prognosis than in PS involvement. In patients with PS involvement a proteasome inhibitor-based regimen may be the best option followed by autologous stem cell transplantation (ASCT) in transplant eligible patients. In patients with EMD disease who are not eligible for ASCT, a proteasome inhibitor-based regimen such as lenalidomide-bortezomib-dexamethasone (RVD) may be the best option, while for those eligible for high-dose therapy a myeloma/lymphoma-like regimen such as bortezomib, thalidomide and dexamethasone (VTD)-RVD/cisplatin, doxorubicin, cyclophosphamide and etoposide (PACE) followed by SCT should be considered. In both EMD and PS disease at relapse many strategies have been tried, but this remains a high-unmet need population.

• MeSH
• Transplantation, Autologous MeSH
• Bortezomib therapeutic use   MeSH
• Cisplatin therapeutic use   MeSH
• Cyclophosphamide therapeutic use   MeSH
• Dexamethasone therapeutic use   MeSH
• Doxorubicin therapeutic use   MeSH
• Etoposide therapeutic use   MeSH
• Lenalidomide therapeutic use   MeSH
• Humans MeSH
• Disease Management MeSH
• Multiple Myeloma complications   diagnosis   pathology   therapy   MeSH
• Plasmacytoma complications   diagnosis   pathology   therapy   MeSH
• Prognosis MeSH
• Antineoplastic Combined Chemotherapy Protocols therapeutic use   MeSH
• Hematopoietic Stem Cell Transplantation MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

BACKGROUND: The emergence of highly active novel agents has led some to question the role of autologous haematopoietic stem-cell transplantation (HSCT) and subsequent consolidation therapy in newly diagnosed multiple myeloma. We therefore compared autologous HSCT with bortezomib-melphalan-prednisone (VMP) as intensification therapy, and bortezomib-lenalidomide-dexamethasone (VRD) consolidation therapy with no consolidation. METHODS: In this randomised, open-label, phase 3 study we recruited previously untreated patients with multiple myeloma at 172 academic and community practice centres of the European Myeloma Network. Eligible patients were aged 18-65 years, had symptomatic multiple myeloma stage 1-3 according to the International Staging System (ISS), measurable disease (serum M protein >10 g/L or urine M protein >200 mg in 24 h or abnormal free light chain [FLC] ratio with involved FLC >100 mg/L, or proven plasmacytoma by biopsy), and WHO performance status grade 0-2 (grade 3 was allowed if secondary to myeloma). Patients were first randomly assigned (1:1) to receive either four 42-day cycles of bortezomib (1·3 mg/m2 administered intravenously or subcutaneously on days 1, 4, 8, 11, 22, 25, 29, and 32) combined with melphalan (9 mg/m2 administered orally on days 1-4) and prednisone (60 mg/m2 administered orally on days 1-4) or autologous HSCT after high-dose melphalan (200 mg/m2), stratified by site and ISS disease stage. In centres with a double HSCT policy, the first randomisation (1:1:1) was to VMP or single or double HSCT. Afterwards, a second randomisation assigned patients to receive two 28-day cycles of consolidation therapy with bortezomib (1·3 mg/m2 either intravenously or subcutaneously on days 1, 4, 8, and 11), lenalidomide (25 mg orally on days 1-21), and dexamethasone (20 mg orally on days 1, 2, 4, 5, 8, 9, 11, and 12) or no consolidation; both groups received lenalidomide maintenance therapy (10 mg orally on days 1-21 of a 28-day cycle). The primary outcomes were progression-free survival from the first and second randomisations, analysed in the intention-to-treat population, which included all patients who underwent each randomisation. All patients who received at least one dose of study drugs were included in the safety analyses. This study is registered with the EU Clinical Trials Register (EudraCT 2009-017903-28) and ClinicalTrials.gov (NCT01208766), and has completed recruitment. FINDINGS: Between Feb 25, 2011, and April 3, 2014, 1503 patients were enrolled. 1197 patients were eligible for the first randomisation, of whom 702 were assigned to autologous HSCT and 495 to VMP; 877 patients who were eligible for the first randomisation underwent the second randomisation to VRD consolidation (n=449) or no consolidation (n=428). The data cutoff date for the current analysis was Nov 26, 2018. At a median follow-up of 60·3 months (IQR 52·2-67·6), median progression-free survival was significantly improved with autologous HSCT compared with VMP (56·7 months [95% CI 49·3-64·5] vs 41·9 months [37·5-46·9]; hazard ratio [HR] 0·73, 0·62-0·85; p=0·0001). For the second randomisation, the number of events of progression or death at data cutoff was lower than that preplanned for the final analysis; therefore, the results from the second protocol-specified interim analysis, when 66% of events were reached, are reported (data cutoff Jan 18, 2018). At a median follow-up of 42·1 months (IQR 32·3-49·2), consolidation therapy with VRD significantly improved median progression-free survival compared with no consolidation (58·9 months [54·0-not estimable] vs 45·5 months [39·5-58·4]; HR 0·77, 0·63-0·95; p=0·014). The most common grade ≥3 adverse events in the autologous HSCT group compared to the VMP group included neutropenia (513 [79%] of 652 patients vs 137 [29%] of 472 patients), thrombocytopenia (541 [83%] vs 74 [16%]), gastrointestinal disorders (80 [12%] vs 25 [5%]), and infections (192 [30%] vs 18 [4%]). 239 (34%) of 702 patients in the autologous HSCT group and 135 (27%) of 495 in the VMP group had at least one serious adverse event. Infection was the most common serious adverse event in each of the treatment groups (206 [56%] of 368 and 70 [37%] of 189). 38 (12%) of 311 deaths from first randomisation were likely to be treatment related: 26 (68%) in the autologous HSCT group and 12 (32%) in the VMP group, most frequently due to infections (eight [21%]), cardiac events (six [16%]), and second primary malignancies (20 [53%]). INTERPRETATION: This study supports the use of autologous HSCT as intensification therapy and the use of consolidation therapy in patients with newly diagnosed multiple myeloma, even in the era of novel agents. The role of high-dose chemotherapy needs to be reassessed in future studies, in particular in patients with undetectable minimal residual disease after four-drug induction regimens including a monoclonal antiboby combined with an immunomodulatory agent and a proteasome inhibitor plus dexamethasone. FUNDING: Janssen and Celgene.

• MeSH
• Transplantation, Autologous methods   mortality   MeSH
• Bortezomib administration & dosage   therapeutic use   MeSH
• Dexamethasone administration & dosage   therapeutic use   MeSH
• Gastrointestinal Diseases chemically induced   epidemiology   MeSH
• Infections chemically induced   epidemiology   MeSH
• Injections, Subcutaneous MeSH
• Administration, Intravenous MeSH
• Consolidation Chemotherapy methods   MeSH
• Lenalidomide administration & dosage   therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Melphalan administration & dosage   therapeutic use   MeSH
• Multiple Myeloma diagnosis   drug therapy   MeSH
• Myeloma Proteins analysis   MeSH
• Neutropenia chemically induced   epidemiology   MeSH
• Plasmacytoma pathology   MeSH
• Prednisone administration & dosage   therapeutic use   MeSH
• Disease-Free Survival MeSH
• Antineoplastic Combined Chemotherapy Protocols therapeutic use   MeSH
• Neoplasm Staging MeSH
• Hematopoietic Stem Cell Transplantation adverse effects   mortality   MeSH
• Thrombocytopenia chemically induced   epidemiology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH

• MeSH
• Endosonography MeSH
• Fatal Outcome MeSH
• Shock, Hemorrhagic diagnosis   etiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Pancreatic Neoplasms complications   diagnosis   pathology   MeSH
• Pancreas diagnostic imaging   pathology   MeSH
• Plasmacytoma complications   diagnosis   pathology   MeSH
• Tomography, X-Ray Computed MeSH
• Hypertension, Portal diagnosis   etiology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Review MeSH

The current study assesses the characteristics and outcomes of multiple myeloma (MM) patients, treated with novel agents for hematogenous extramedullary (HEMM) relapse. Consecutive patients diagnosed with HEMM between 2010-2018 were included. Patients' characteristics at diagnosis and at HEMM presentation, response to treatment, survival and factors predicting survival were recorded and analyzed. A group of 127 patients, all diagnosed with HEMM by imaging (87.3%) and/or biopsy (79%), were included. Of those, 44% were initially diagnosed with ISS3, 57% presented with plasmacytomas, and 30% had high-risk cytogenetics. Median time to HEMM was 32 months. In multivariate analysis, ISS3 and bone plasmacytoma predicted shorter time to HEMM (P = .005 and P = .008, respectively). Upfront autograft was associated with longer time to HEMM (P = .002). At HEMM, 32% of patients had no BM plasmacytosis, 20% had non-secretory disease and 43% had light-chain disease. Multiple HEMM sites were reported in 52% of patients, mostly involving soft tissue, skin (29%), and pleura/lung (25%). First treatment for HEMM included proteasome inhibitors (50%), immunomodulatory drugs (IMiDs) (39%), monoclonal antibodies (10%), and chemotherapy (53%). Overall response rate (ORR) was 57%. IMiDs were associated with higher ORR (HR 2.2, 95% CI 1.02-4.7, P = .04). Median survival from HEMM was 6 months (CI 95% 4.8-7.2). Failure to achieve ≥VGPR was the only significant factor for worse OS in multivariate analyses (HR = 9.87, CI 95% 2.35 - 39, P = .001). In conclusion, HEMM occurs within 3 years of initial myeloma diagnosis and is associated with dismal outcome. The IMiDs might provide a higher response rate, and achievement of ≥VGPR predicts longer survival.

• MeSH
• Autografts MeSH
• Central Nervous System pathology   MeSH
• Progression-Free Survival MeSH
• Adult MeSH
• Immunologic Factors administration & dosage   MeSH
• Proteasome Inhibitors administration & dosage   MeSH
• Liver pathology   MeSH
• Kaplan-Meier Estimate MeSH
• Combined Modality Therapy MeSH
• Skin pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymph Nodes pathology   MeSH
• Multiple Myeloma blood   drug therapy   pathology   therapy   MeSH
• Neoplastic Cells, Circulating * MeSH
• Neoplastic Stem Cells pathology   MeSH
• Bone Neoplasms blood   drug therapy   pathology   therapy   MeSH
• Organ Specificity MeSH
• Plasma Cells pathology   MeSH
• Plasmacytoma blood   drug therapy   pathology   therapy   MeSH
• Pleura pathology   MeSH
• Lung pathology   MeSH
• Proportional Hazards Models MeSH
• Antineoplastic Agents, Immunological administration & dosage   MeSH
• Antineoplastic Combined Chemotherapy Protocols therapeutic use   MeSH
• Recurrence MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Hematopoietic Stem Cell Transplantation MeSH
• Salvage Therapy methods   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH