SDC1 positive

Unfortunately, our patient died one month after the initial diagnosis. We present also a review of the recent literature in order to highlight the clinical presentations of the myelomatous pleural effusion, the diagnostic tools, the therapeutic strategies as well as the outcomes.

Overall, 73.1% (49/67) of cervical cancer samples are CD138-positive with 38.8% (26/67) of cervical cancer samples showing at least moderate or high expression. (4) TROP2, CEACAM5 or CD138 do seem suitable for further clinical research and the data presented here might be used to guide further clinical trials with ADCs in advanced and recurrent cervical cancer patients.

ALK + LBCL can present with an ambiguous immunophenotype, which warrants the use of multiple B cell, T cell, and plasmacytic antibodies. CD3 expression in this entity is rare and of uncertain clinical significance, but warrants further study.

An increased number of mutations detected in cfDNA were associated with a decreased overall survival. In conclusion, we demonstrated cfDNA NGS analysis feasibility and accuracy in R/R MM patients who may benefit from early phase clinical trial.

The "immuno-flowFISH" imaging flow cytometric method could detect del(17p) in plasma cells in both bone marrow and blood samples of myeloma patients. This method was also able to detect gains and losses of chromosome 17, which are also of prognostic significance. The lowest levels of 0.009% (bone marrow) and 0.001% (blood) for chromosome 17 abnormalities was below the detection limit of current FISH method. This method offers potential as a new means of identifying these prognostically important chromosomal defects, even when only rare cells are present and for serial disease monitoring.

Overall survival of our patients was 4.1 months and overall survival of patients treated with VTD (bortezomib, thalidomide, dexamethasone) and VCD (bortezomib, cyclophosphamide, dexamethasone) regimen was 3.4 and 4.1 months, respectively, which was not statically significant ( p -value 0.816). Conclusion  Because of rarity of the disease, prospective studies are very limited and hence management and outcome of the disease are difficult to analyze. The current treatment protocols have no survival advantage and hence newer therapeutic approach is mandatory to attain better outcome.

Plasmablastic neoplasms remain a heterogeneous group of diseases with a historically poor prognosis. Our PBL patients showed an improved OS at 12 months of 80% compared to the SEER database PBL OS of 56%. This improvement in survival could derive from ethnic variations in tumor biology in this predominantly Hispanic cohort, which is consistent with the improved OS in Hispanic patients seen in the SEER database.

Cytoplasmic cyclin D1 expression may be related to lack of cyclin D1 protein degradation by a defective UBA1 gene product. Our results suggest that defective UBA1 and autoinflammation pose an increased risk for developing MGUS or multiple myeloma.

The flow cytometric analysis allowed to discover the non-hematological nature of this population, circulating at high level in peripheral blood. Aspirate smears revealed the presence of the same cells, and immunohistochemistry on bone marrow confirmed the massive infiltration of breast cancer cells, allowing to diagnose bone marrow metastases.

Pts with RRMM who received 2-4 prior regimens, were TCE (IMiD agent, PI, and daratumumab), and had disease refractory to the last regimen were randomized 2:1 to receive ide-cel (target dose range: 150-450×106 CAR+ T cells) or a std regimen (DPd, DVd, IRd, Kd, or EPd per investigator). Presented previously at European Haematology Association Hybrid Congress, June 2023 Clinical Trial Identification: NCT03651128. Table 1.

He received one cycle of CyBorD (Cyclophosphamide, Bortezomib, Dexamethasone), followed by seven cycles of KCD (Carfilzomib, Cyclophosphamide, Dexamethasone) and Rituximab...The patient was treated with Acalabrutinib, and his anemia, epistaxis, and coagulopathy resolved...In contrast to our patient, who has LPL with IgG Monoclonal gammopathy, approximately 95 percent of LPL patients have IgM Monoclonal gammopathy, which corresponds with WM. As a result, clinicians should be on the lookout for LPL that lacks an IgM Monoclonal Paraprotein.

Cytoplasmic cyclin D1 expression may be related to lack of cyclin D1 protein degradation by a defective UBA1 gene product. Our results suggest that defective UBA1 and autoinflammation pose an increased risk for developing MGUS or multiple myeloma.

This study represents the first US-based multicenter prospective evaluation of the GEP SKY92 in a real-world clinical setting. The results obtained align with the retrospective validations of SKY92, further confirming its reliability as a prognostic marker for MM patients. In addition, we observed that the SKY92 is able to identify a higher number of high-risk patients, with significantly shorter PFS and OS, compared to the conventional R-ISS staging system.

Finally, we also demonstrated that treatment with the hypomethylating agent azacytidine can drive increased CD70 expression, similar to that shown in AML models. Taken together, targeting CD70 appears to be a highly promising cellular therapeutic strategy for MM, with particularly high utility in high-risk patients after BCMA CAR-T relapse. We are continuing preclinical and future clinical development of this CAR-T strategy, using our natural ligand CD27 design with extended in vivo persistence.

These findings based on prospective real-world clinical data, collected in a prospective US multicenter trial confirm the effectiveness of the GEP SKY92 on risk stratification both for PFS and OS. These results support the added value of integrating SKY92 into clinical practice for precise risk assessment of patients. Figure1: PFS and OS based on the combination of the clinical risk assessment (CRA) and the SKY92 risk.

These results indicate distinct bone marrow microenvironments of HR and SR MM. CD4 and CD8 T cells appear to be more activated in HR patients compared to SR. However, the higher frequencies of mast cells and plasmacytoid dendritic cells, and the prominent expression of ISGs associated with inhibition of anti-tumor immunity suggest dysregulation and exhaustion of T cell activity in HR patients.

This study demonstrates differential DNA methylation of key genomic regions in WM compared to IgM-MGUS. Promotor methylation-based analysis reveals hypomethylation of several important cellular pathways involved in cytokine signaling, cell structure/ECM, and intracellular signaling. These results underscore the influence of epigenetics in the IgM-gammopathy disease spectrum and suggest the potential role of aberrant DNA methylation underlying the malignant progression from IgM-MGUS to WM.

Refractoriness to specific drugs was observed, such as bortezomib (49%), carfilzomib (27%), lenalidomide (49%), pomalidomide (33%), daratumumab (49). By incorporating critical information on drug resistance patterns and expression of key targets like GPRC5D, TNFRSF17 (BCMA) and FcRH5, we enable precision medicine approaches for improved management of relapsed refractory myeloma. These findings open avenues for tailored and more effective therapeutic strategies, promising better outcomes for patients with relapsed refractory myeloma.

Taken together, we achieved a complete view of MM diversity by using repertoire clonality and confirmed heterogeneity along the CD138 axis, which may be characterized by epigenetic plasticity. Our results highlight a novel subpopulation as a candidate therapeutic target for cure.

Moreover, HR SKY92 was significantly more common in patients who received high-dose melphalan (48/89, 53.9%) than the remaining patients (9/32, 28.1%) ( P =0.01)...We found CRBN mutation in 3 out of 7 patients with only HR SKY92 but SR FISH. We provide the first prospective evidence that “double-HR” (SKY92 + FISH according to R2-ISS) indicates the highest-risk MM.

The results of this study indicate that in the diagnostic work-up of MM, MFC may help to identify different patient subsets and improve risk stratification. These observations need to be validated in larger series of patients with a longer follow-up.

The patient was diagnosed with lymphoplasmacytic lymphoma based on cell morphology and CD20-positivity and was treated with five cycles of a bendamustine-rituximab regimen for 17 months. Small cell-variant plasma cell myeloma could be misdiagnosed as other mature B-cell neoplasms owing to its small lymphocyte-like morphology, frequent CD20-positivity, and frequent light chain type that lacks a rouleaux formation. Flow cytometric immunophenotyping and IHC for CD45 and CD138 may assist in the differential diagnosis.

In the largest to date single-cell RNA-sequencing study of immune cells from patients with monoclonal gammopathies, we have comprehensively mapped alterations in BM immune cell composition in patients with MGUS, identified subpopulations that are more likely to interact directly with tumor cells in the BM microenvironment, and described immune hallmarks of disease.

At relapse they received daratumumab based salvage in combination with lenalidomide and then pomalidomide...The first profiled bone marrow was collected during leukapheresis for cilta-cel but due to progressive disease the patient received an FCRL5 directed bispecific, and a second sample was collected at progression after a brief sCR to this agent... This case represents the first known bi-allelic loss of CD38 and acquired loss of FCRL5 expression. These events, along with the loss of BCMA highlight the need for more advanced clinical testing to assess the actionability of the diverse therapeutic targets available to treat patients today.

Moreover, HR SKY92 was more common in patients who received high-dose melphalan and autologous stem cell transplant (48/89, 53.9%) than the remaining patients (9/32, 28.1%) (P=0.01)... We provide the first prospective evidence that "double-HR" (SKY92 + FISH according to R2-ISS) indicates the highest-risk MM.

Our case highlights the rare association of monotypic IgG4 expression within a subset of dural marginal zone lymphomas, previously reported in only 1 case series. Our patient was not known to have a preexisting IgG4-related sclerosing disease or other autoimmune condition, underscoring the possibility that such lesions may represent de novo IgG4+ marginal zone lymphomas.

PD-1–positive TFH cell proliferation, although not specific, is a feature associated with peripheral T-cell lymphomas of TFH cell derivation, which increases diagnostic difficulties for MZL. Next-generation sequencing for lymphoma panel shows a pathogenic variant of TNFSRF14 C.215 G>A that has been reported in diffused large B-cell lymphoma but not in nodal MZL with plasmacytic differentiation.

We report the case of a 70-year-old man with IgA lambda multiple myeloma treated with daratumumab, cyclophosphamide, bortezomib, dexamethasone (DaraCyBorD) and carfilzomib, pomalidomide, dexamethasone (KPomD) who presented with altered mental status and severe generalized weakness. Histology in such cases shows sinusoidal flooding by neoplastic plasma cells with little or no propensity to destroy the underlying liver parenchyma. Radiographic imaging is usually unable to detect this diffuse infiltrative pattern; therefore, a liver biopsy is essential to make a diagnosis.

CTS may be an early sign of systemic amyloidosis. Congo red stain should be performed on tenosynovial tissue at the time of carpal tunnel release surgery.

Patients: In KarMMa-3, patients with RRMM who had received 2 to 4 prior regimens, were TCE (immunomodulatory agent, proteasome inhibitor [PI], daratumumab), and had disease refractory to the last regimen were randomized to ide-cel or standard regimen. Ide-cel treatment showed lower risk of disease progression or death and higher response rates (ORR and CRR) vs standard regimens. Results support use of ide- cel in patients with TCE RRMM, including those with high-risk disease.

Histopathological evaluation was consistent with Plasmacytoma and IHC was strongly positive for CD 138. Her thorough evaluation for Multiple myeloma was negative.

We were able to successfully count CD138-positive plasma cells in bone marrow biopsies using artificial intelligence. This method is superior to both manual counting and overview estimation, regardless of tumour load.

Based on polyclonal growth pattern of lymphocytes in the lymphoid follicles and interfollicular region, she was diagnosed with hepatic reactive lymphoid hyperplasia (RLH).Review of the English literature of hepatic RLH which referred to imaging findings yielded 23 cases, including this case. As a result, we suggest that liver biopsy should be performed for definitive diagnosis, when hepatic RLH is suspected by imaging findings and backgrounds.

Patients who received neoadjuvant CROSS (carboplatin, paclitaxel and intensity modulated radiotherapy) therapy and had CD138-positive tumours lived significantly longer (P=0.04)...In conclusion, CD138 in cancer is already used as a target for ADCs, such as indatuximab ravtansine, the effectiveness of which depends on the extent of CD138 on tumour cells...Regardless of the favourable prognostic effect of CD138 in EAC, there is an urgent clinical need for personalized therapeutics in relapse. Future clinical trials now need to show how effective the corresponding ADCs are in CD138-positive EACs.

Bilateral pleural catheters were placed, and the patient was discharged on daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) with a plan for autologous stem cell transplant. It is important to keep a broad differential for a patient presenting with pleural effusions. As EMD in MM can have variable presentations, recognizing myelomatous pleural effusions early is required to start appropriate therapy to treat the underlying cause.

Suspecting and diagnosing MPE with specific tests in patients with MM is essential to provide appropriate and timely management options. They also could warrant IPC like other malignant pleural effusions.

Extramedullary solitary plasmacytoma of the breast is extremely rare. This case report seeks to educate clinicians about the rare possibility of extramedullary plasmacytoma in the breast, and it should be considered in the differential for a breast lump, especially in patients with autoimmune hepatitis and on azathioprine. Standard treatment for EMP consists of radiation due to high sensitivity and cure rate.

We demonstrate the possibility to specifically target MM cells, even after CD38 targeted therapy, with carefully-designed dual-split CARs directed against CD38 and CD138.