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Viruses can be engineered or adapted for selective propagation in neoplastic tissues and further modified for therapeutic transgene expression to enhance their antitumor potency and druggability. Oncolytic viruses (OVs) can be administered locally or intravenously and spread to a variable degree at sites of tumor growth. OV-infected tumor cells die in situ, releasing viral and tumor antigens that are phagocytosed by macrophages, transported to regional lymph nodes, and presented to antigen-reactive T cells, which proliferate before dispersing to kill uninfected tumor cells at distant sites. Several OVs are showing clinical promise, and one of them, talimogene laherparepvec (T-VEC), was recently granted marketing approval for intratumoral therapy of nonresectable metastatic melanoma. T-VEC also appears to substantially enhance clinical responsiveness to checkpoint inhibitor antibody therapy. Here, we examine the T-VEC paradigm and review some of the approaches currently being pursued to develop the next generation of OVs for both local and systemic administration, as well as for use in combination with other immunomodulatory agents. Russell and Peng review the field of oncolytic virotherapy, highlighting the recent approval of intralesional talimogene laherparepvec (T-VEC) for metastatic melanoma and its synergistic interaction with checkpoint inhibitor antibodies. They then explore how newer OVs may further improve treatment outcomes in the post-T-VEC era.

PurposeDespite the development of novel drugs and the widespread use of hematopoietic cell transplantation, the prognosis of patients (pts) with multiple myeloma and extramedullary involvement (soft-tissue plasmacytoma, STP) is rather unfavorable.MethodsA retrospective analysis of 120 pts with STP treated between 2007 and 2022 was performed. The effects of demographic and clinical characteristics on treatment response, progression-free survival (PFS), and overall survival (OS) were evaluated.ResultsThe rate of serological response to first-line STP treatment (at least partial remission) was 67%, and the rate of imaging response was 59%. With a median follow-up of 84.2 months, the median PFS was 10.5 months (primary STP: 20.2 months; secondary STP: 5.8 months), and the median OS was 24.5 months (primary STP: 34.5 months; secondary STP: 12.4 months). Based on the multivariate regression analysis, secondary STP (HRPFS 2.75; HROS 2.63) and organ involvement (HRPFS 1.45; HROS 1.68) were found to be negative prognostic factors of both PFS and OS. In a prognostic model, pts with at least one of these factors had a significantly worse PFS (HRPFS 3.31) and OS (HROS 3.45) than those with none risk factor.ConclusionIn pts with STP, risk-adapted treatment strategies including immunotherapies and cell therapies are urgently required.

PurposeSolitary plasmacytoma (SP) is a rare plasma-cell neoplasm, which can develop both in skeletal and/or soft tissue and frequently progresses to multiple myeloma (MM). Our aim was to study the metabolic behavior of SP and the role of 18F–FDG-PET/CT in predicting progression to MM.Materials and methodsSixty-two patients with SP who underwent 18F–FDG-PET/CT before any treatment were included. PET images were qualitatively and semiquantitatively analyzed by measuring the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and compared with age, sex, site of primary disease, and tumor size.ResultsFifty-one patients had positive 18F–FDG-PET/CT (average SUVbw was 8.3 ± 4.7; SUVlbm 5.8 ± 2.6; SUVbsa 2 ± 1; MTV 45.4 ± 37; TLG 227 ± 114); the remaining 11 were not 18F–FDG-avid. Tumor size was significantly higher in patients avid lesions compared to FDG not avid; no other features are associated with FDG-avidity. Progression to MM occurred in 29 patients with an average of 18.3 months; MM was more likely to develop in patients with bone plasmacytoma and in patients with 18F–FDG avid lesion. Time to transformation in MM (TTMM) was significantly shorter in patients with osseous SP, in 18F–FDG avid lesion, for SUVlbm > 5.2 and SUVbsa > 1.7.Conclusions18F–FDG pathological uptake in SP occurred in most cases, being independently associated with tumor size. PET/CT seemed to be correlated to a higher risk of transformation in MM, in particular for 18F–FDG avid plasmacytoma and SBP. Among semiquantitative features, SUVlbm > 5.2 and SUVbsa > 1.7 were significantly correlated with TTMM.

Extramedullary Plasmacytoma (EMP) is a rare plasma cell neoplasm that originates outside the bone marrow. Primary Extramedullary Plasmacytoma with Diffuse Lymph Node Involvement (PLNEMP) is exceptionally rare. Here, we report a unique case of PLNEMP and significant bone destruction, characterized by a novel IGH::NFKB1 fusion gene. A 60-year-old Chinese male presented with palpable enlarged lymph nodes in the left inguinal region. After completing laboratory tests and examinations, it was suggested that there was monoclonal immunoglobulinemia and multiple bone destruction. Pathological examination of the left inguinal lymph node biopsy showed plasmacytoma with monoclonal gammopathy. Genomic profiling identified a novel IGH::NFKB1 fusion gene. The two 3′ regulatory region (3′RR) enhancers of the IGH locus were fused to a region 379 bp upstream of NFKB1 exon 1, resulting in overexpression of NFKB1 . The patient received four cycles of chemotherapy with Mitoxantrone hydrochloride liposome (Lipo-MIT) combined with Bortezomib, Pomalidomide, and Dexamethasone (MVPD), achieving very good partial remission (VGPR) in hematological and partial remission (PR) in extramedullary disease. Subsequently, he underwent autologous stem cell transplantation (ASCT) followed by BCMA CAR-T cell therapy. At 8 months post-transplantation, complete remission (CR) was achieved in hematological parameters, and the extramedullary disease showed a response greater than PR. The patient has survived for 26 months so far. This case highlights the importance of recognizing the rare presentation of PEMP with diffuse lymph node involvement and significant bone destruction. The presence of the novel IGH::NFKB1 fusion gene provides insights into the potential role of the NF-κB pathway in the pathogenesis of this disease. The successful treatment with MVPD chemotherapy, ASCT, and BCMA CAR-T therapy demonstrates the potential efficacy of this combined therapeutic approach in achieving long-term remission and survival in such rare cases. Further studies are warranted to explore the therapeutic implications of targeting the NF-κB pathway in similar cases of EMP with bone destruction.

Background Solitary plasmacytoma (SP) is a localized neoplastic plasma cell disorder with an annual incidence of less than 450 cases. Given the rarity of this disorder, it is difficult to conduct large-scale population studies. Consequently, very limited information on the disorder is available, making it difficult to estimate the incidence and survival rates. Furthermore, limited information is available on the efficacy of various treatment modalities in relation to primary tumor sites. Methods The data for this retrospective study were drawn from the Surveillance, Epidemiology and End Results (SEER) database, which comprises 18 registries; patient demographics, treatment modalities and survival rates were obtained for those diagnosed with SP from 1998 to 2007. Various prognostic factors were analyzed via Kaplan-Meier analysis and log-rank test, with 5-year relative survival rate defined as the primary outcome of interest. Cox regression analysis was employed in the multivariate analysis. Results The SEER search from 1998 to 2007 yielded records for 1691 SP patients. The median age at diagnosis was 63 years. The patient cohort was 62.4% male, 37.6% female, 80% Caucasian, 14.6% African American and 5.4% other races. Additionally, 57.8% had osseous plasmacytoma, and 31.9% had extraosseous involvement. Unspecified plasmacytoma was noted in 10.2% of patients. The most common treatment modalities were radiotherapy (RT) (48.8%), followed by combination surgery with RT (21.2%) and surgery alone (11.6%). Univariate analysis of prognostic factors revealed that the survival outcomes were better for younger male patients who received RT with surgery ( p  < 0.05). Additionally, patients who received neoadjuvant RT had increased survival rates compared to those receiving adjuvant RT (86% vs 73%, p  < 0.05). Furthermore, the analyses revealed that 5-year survival rates for patients with axial plasmacytoma were superior when RT was combined with surgery ( p  < 0.05). In the multivariate analysis, age <60 years and treatment with either RT or surgery showed superior survival rates. Progression to multiple myeloma (MM) was noted in 551 patients. Age >60 years was associated with a lower 5-year survival in patients who progressed to MM compared to those who were diagnosed initially with MM (15.1 vs 16.6%). Finally, those who received RT and progressed to MM still had a higher chance of survival than those who were diagnosed with MM initially and treated with RT/surgery (21.8% vs 15.9%, p  < 0.05). Conclusions A review of the pertinent literature indicates that we provided the most comprehensive population-based analysis of SP to date. Moreover, our study contributes to the establishment of the optimal SP treatment modality, as RT is the favored option in frontline settings. Consensus is currently lacking regarding the benefits of combined treatment including surgery. Thus, the findings reported here elucidate the role of primary treatment modalities while also demonstrating the quantifiable benefits of combining RT with surgery in relation to different primary tumor sites. While our results are promising, they should be confirmed through further large-scale randomized studies.

Background Adrenal extramedullary plasmacytoma (EMP) is an exceptionally rare plasma cell neoplasm with fewer than 20 documented cases worldwide. The clinical presentation, optimal management strategies, and long-term outcomes remain poorly defined. Case presentation We report the case of a 51-year-old woman with synchronous bone and adrenal EMP, without multiple myeloma. The initial presentation involved pathological humeral fracture following minor trauma, with the subsequent discovery of a 40 mm left adrenal mass on staging CT. Emergency orthopedic fixation and bone biopsy confirmed the diagnosis of EMP. Immunohistochemical findings showed CD138, MUM1, and kappa light-chain restriction positivity, with negative lambda staining. After declining initial surgical intervention, the patient was lost to follow-up for two years, during which the adrenal lesion enlarged to 70 mm. Comprehensive staging including bone marrow biopsy, FDG-PET/CT, and laboratory workup confirmed absence of multiple myeloma features according to International Myeloma Working Group criteria. Complete laparoscopic left adrenalectomy was successfully performed, with uncomplicated recovery. Histopathological examination revealed a 75 × 55 × 30 mm encapsulated mass with characteristic plasma cell morphology and extensive hemorrhagic foci. The Ki-67 proliferation index was < 10% and Congo red staining was positive. Adjuvant lumbo-aortic radiotherapy (45 Gy) was administered. The patient achieved complete clinical and radiological responses at three-month follow-up. Conclusions Synchronous EMP without multiple myeloma is an exceptionally rare entity that requires comprehensive systemic evaluation and multidisciplinary management. Contemporary management favors laparoscopic resection combined with adjuvant radiotherapy for optimal local control. Excellent survival outcomes support aggressive therapy, although lifelong surveillance remains essential given the potential progression to systemic disease.

BackgroundExtramedullary plasmacytoma (EMP) is a rare solitary malignancy that accounts for 3% of plasma cell neoplasms, and EMP with a primary occurrence in the palate is extremely uncommon. Owing to the long course of EMP and the limited available data on treatment outcomes, there are no definitive guidelines for its management, especially for high-risk patients who are more susceptible to early progression to multiple myeloma.Case presentationIn this study, we review nine relevant studies and describe a 54-year-old woman who presented with an asymptomatic nonulcerative mass localized in the palate. After initial radical surgical resection of the lesion, the patient was definitively diagnosed with EMP with minimal plasmacytosis in the bone marrow, and adjuvant intensity-modulated radiation therapy with a minimum dose of 39.6 Gy was administrated in the surgical area. There was no evidence of local recurrence, nodal metastasis or progression to multiple myeloma (MM) during the seven-year follow-up period.ConclusionGiven the atypical clinical features of palate EMP reported in the literature and the encouraging results of our patient, sequential therapy involving surgery and adjuvant radiotherapy for primary palatal lesions in high-risk EMP patients without nodal involvement could be an effective treatment modality.

Limited real-world studies have compared radiation therapy (RT) to non-RT for patients with solitary plasmacytoma of bone (SPB). This study investigated the impact of RT on long-term survival outcomes in patients with SPB at the pre-B cell grade within a real-world context. We conducted a retrospective cohort analysis using data from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with SPB at the pre-B cell grade between 2010 and 2017. Patients were categorized into two groups based on receipt of RT. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) to investigate the value of RT for overall survival (OS) and cancer-specific survival (CSS). Survival curves were generated using the Kaplan–Meier method. A total of 1,922 individuals with SPB at the pre-B cell grade met the inclusion and exclusion criteria. Among these, 1,417 (74%) received RT, while 505 (26%) underwent non-RT. Multivariate Cox regression analysis revealed higher rates of OS (HR = 0.64, 95% CI = 0.55–0.74, p  < 0.0001) and CSS (HR = 0.68, 95% CI = 0.56–0.82, p  < 0.0001) in patients who received RT. These results remained consistent across sensitivity and subgroup analyses. Analysis of the SEER database suggests that RT is associated with improved OS and CSS and is the primary treatment for patients with SPB at the pre-B cell grade.

Multiple myeloma (MM) is a complex genetic disease characterized by the heterogeneity of tumor cells. We have measured KRAS, NRAS, and BRAF gene mutations in circulating free tumor DNA (ctDNA) from plasma, bone marrow, and plasmacytoma samples as well as their correlation with various clinical and laboratory parameters. The prospective study included 113 MM patients (74 with plasmacytoma and 39 without), treated at the National Medical Research Center for Hematology (Moscow, Russia) from 2009 to 2024. FISH was performed on CD138+ bone marrow cells for 104 patients and array-CGH for two extramedullary plasmacytoma samples. Mutation analysis on CD138+ bone marrow cells was performed for 99 patients, on ctDNA for 80 patients, and, in 26 cases, samples of plasmacytoma were also investigated. Mutations in the KRAS, NRAS, and BRAF genes either in bone marrow, ctDNA, or plasmacytoma samples were found in 50% of patients. In patients with plasmacytoma, mutations in ctDNA were found in 28% of cases versus 0% in cases without plasmacytoma (p = 0.0007). Rare “noncanonical” KRAS and NRAS gene mutations were also more frequent in ctDNA compared to the bone marrow substrate (50% versus 9%, p = 0.01). Liquid biopsy in MM, particularly identification of the KRAS, NRAS, and BRAF gene mutations in ctDNA, is a valuable instrument for prognostication. Researching the intricate mechanisms underlying extramedullary involvement, and identifying novel high-risk factors associated with the disease, is worthwhile.

Background Extramedullary plasmacytoma (EMP) is a solitary tumor consisting of neoplastic plasma cells, with very little to no bone marrow involvement. EMPs are usually located in the head and neck region, but can also occur along the digestive tract, in lungs, or extremities. Methods Following our publication on EMP, which appeared in 1999 (Cancer 85:2305–14), we conducted a literature search for EMP‐related reports published between 1999 and 2021. The documented cases, as well as 14 of our own patients from the ENT Clinic Erlangen, were extensively analyzed. Results Between 1998 and 2021, 1134 patients with EMP were reported, for whom information about the tumor localization was available. Among those, 62.4% had EMP in the head and neck area and 37.6% in other body regions. Data on therapy were reported in 897 patients, including 34.3% who received radiation, 28.1% surgery, 22.6% a combination of surgery and radiation, and 15.9% another therapy. In 76.9% patients no recurrence or transformation to multiple myeloma (MM) was reported, 12.8% showed local recurrence and 10.2% developed MM. Radiotherapy alone was associated with a tendency for increased occurrence of MM. In patients with EMP of head and neck area, combination therapy (surgery and radiation) resulted in a 5‐year overall survival rate of 98.3%, surgery alone of 92.4%, and radiotherapy of 92.7%. Conclusions Collectively, our analyses indicate that surgical resection alone can achieve long‐term tumor control in patients with EMP, if the tumor can be removed within safe limits without causing serious functional impairment. However, if this is not certain, either radiation or a combination of surgery and radiation therapy is suggested as an effective means of local tumor control. This paper provides an overview of the extramedullary plasmacytoma cases reported between 1999 and 2021. The global patients’ cohort and the current therapy options are compared to our previous report from 1999.