Do Alarmins Have a Role in Multiple Myeloma?

Objective: Calprotectin (CLP), S100A6, and High Mobility Group Nucleosome-Binding Protein 1 (HMGN1), known as alarmins, are involved in the pathogenesis of many tumors. In this study, we aimed to inve stigate the relationship of serum CLP, S100A6, and HMGN1 levels with clinical and laboratory findings in Multiple Myeloma (MM) patients and their role in the pathogenesis of MM. Materials and Methods: We measured serum CLP, S100A6, and HMGN1 levels in 55 newly diagnosed patients and 32 healthy controls (HC). Results: We determined significantly decreased serum CLP, S100A6 ve HMGN1 levels in MM patients compared to HC (p=0.012, p=0.001, p=0.030, respectively). ROC analysis was used to determine a diagnostic cut-off value for serum CLP, S100A6 and HMGN1; the cut off value for CLP was <98 ng/ml (AUC = 0.663, 95% CI 0.554-0.761, p=0.009), S100A6 was <1174.5 pg/ml (AUC = 0.706, 95% CI 0.598-0.799, p=0.001), and HMGN1 was <440.18 pg/ml (AUC = 0.640, 95% CI 0.530-0.740, p:0.03). CLP level was found to be statistically significantly in light chain MM patients ( 91.58±22.57) higher than in heavy chain MM patients (79.42±15.83) (p=0.03). A negative correlation was observed between CLP and M protein, IgG, globulin, and beta 2 microglobulin (correlation coefficient: -0,361; -0,370; -0,279; -0,300, p=0,024, p=006, p=0,04, p=0,0033). Conclusion: In this study, we found that serum CLP, S100A6, and HMGN1 levels were statistically lower in newly diagnosed MM patients compared to HC. These results suggest that CLP may binds to the paraprotein produced by heavy chain MM in the blood and therefore its blood levels are found to be low. Additionally, low levels of HMGN1, which is involved in DNA repair, suggest that HMGN1 may contribute to the complex genetic abnormalities found in MM.

Experience of Daratumumab in Relapsed/Refractory Multiple Myeloma: A Multicenter Study from Türkiye

Objective: This study aimed to evaluate patients with relapsed/refractory multiple myeloma (RRMM) who underwent daratumumab (DARA) therapy. Materials and Methods: This multicenter retrospective study included 134 patients who underwent at least two courses of DARA from February 1, 2018, to April 15, 2022. Epidemiological, disease, and treatment characteristics of patients and treatment-related side effects were evaluated. Survival analysis was performed. Results: The median age at the start of DARA was 60 (range: 35-88), with 56 patients (41.8%) being female and 48 (58.2%) being male. The median time to initiation of DARA and the median follow-up time were 41.2 (5.1-223) and 5.7 (2.1-24.1) months, respectively. The overall response rate after DARA therapy was 75 (55.9%), and very good partial response or better was observed in 48 (35.8%) patients. Overall survival (OS) and progression-free survival (PFS) for all patients were 11.6 (7.8-15.5) and 8.0 (5.1-10.9) months, respectively. OS was higher for patients undergoing treatment with DARA and bortezomib-dexamethasone (DARA-Vd) compared to those undergoing treatment with DARA and lenalidomide-dexamethasone (DARA-Rd) (16.9 vs. 8.3 months; p=0.014). Among patients undergoing DARA-Rd, PFS was higher in those without extramedullary disease compared to those with extramedullary disease (not achieved vs. 3.7 months; odds ratio: 3.4; p<0.001). The median number of prior therapies was 3 (1-8). Initiation of DARA therapy in the early period provided an advantage for OS and PFS, although it was statistically insignificant. Infusion-related reactions were observed in 18 (13.4%) patients. All reactions occurred during the first infusion and most reactions were of grade 1 or 2 (94.5%). The frequency of neutropenia and thrombocytopenia was higher in the DARA-Rd group (61.9% vs. 24.7%, p<0.001 and 42.9% vs. 15.7%, p<0.001). Conclusion: Our study provides real-life data in terms of DARA therapy for patients with RRMM and supports the early initiation of DARA therapy.

Correction to: Efects of AGEs, sRAGE and HMGB1 on Clinical Outcomes in Multiple Myeloma.

[This corrects the article DOI: 10.1007/s12288-022-01574-6.].

Effects of AGEs, sRAGE and HMGB1 on Clinical Outcomes in Multiple Myeloma.

Purpose: The receptor for advanced glycation end products (RAGE) upregulated during the onset and progression of cancer and bone-related pathologies. In this study, we aimed to investigate the role of serum advanced glycation end products (AGEs), soluble RAGE (sRAGE) and high mobility group box 1 (HMGB1), in multiple myeloma (MM). Methods: AGEs, sRAGE and HMGB1 concentrations of 54 newly diagnosed MM patients and 30 healthy volunteers were measured by ELISA. The estimations were done only once at diagnosis. The medical records of the patients were evaluated. Results: There was no significant difference between the AGEs and sRAGE levels between the patient and control groups (p = 0.273, p = 0.313). In ROC analysis, a HMGB1 cutoff value of > 9170 pg/ml accurately discriminated MM patients (AUC = 0.672, 95% CI 0.561-0.77, p = 0.0034). AGEs level was found to be significantly higher in early-stage disease and HMGB1 in advanced disease (p = 0.022, p = 0.026). High HMGB1 levels were detected in patients whose with better first-line treatment response (p = 0.019). At 36 months, 54% of patients with low AGE were alive, compared to 79% of patients with high AGE (p = 0.055). Patients with high HMGB1 levels tended to have a longer PFS (median 43 mo [95% CI; 20.68-65.31] ) compared to patients with low HMGB1 levels (median 25 mo [95% CI; 12.39-37.6], p = 0.054). Conclusion: In this study, a significant elevation of serum HMGB1 level was found in MM patients. In addition, the positive effects of RAGE ligands on treatment response and prognosis were determined.

Ocular manifestations in hemodialysis patients and short-term changes in ophthalmologic findings.

The purpose of this study was to investigate the frequency of ocular manifestations in hemodialysis (HD) patients and short-term changes in ophthalmologic findings. A total of 142 eyes of 71 HD patients were included in this study. Patients with corneal and conjunctival deposits, diabetic retinopathy, hypertensive retinopathy, cataract, optic atrophy, or glaucoma were recorded. Schirmer I tests and the tear break up time (TBUT) were performed in the listed order to evaluate dry eye. Axial length (AL) and anterior chamber depth (ACD) were measured using ultrasound biometry using an infrared system. The TBUT test, Schirmer I test, intraocular pressure, AL, and ACD were applied within 30 minutes before and after a single session of HD. The most common ocular findings included conjunctival calcification (60.6%), cataract (50.7%), and proliferative diabetic retinopathy (21.1%). The average TBUT results decreased from 10.81 ± 4.90 to 9.43 ± 4.78 seconds after HD, and was statistically significant (P < .001). The mean Schirmer I test results decreased from 13.59 ± 4.67 to 12.07 ± 4.86 mm after HD. The decline in the Schirmer I test results was statistically significant (P = .005). The mean intraocular pressure decreased from 14.57 ± 4.40 to 13.43 ± 3.91 mm Hg after HD, and was statistically significant (P < .001). The mean ACD increased from 3.19 ± 0.53 to 3.25 ± 0.55 mm, and the mean AL increased from 23.05 ± 1.35 to 23.13 ± 1.35 mm, both increases being significant after HD (both P < .001). Eye diseases such as diabetic retinopathy, corneo-conjunctival calcification, and dry eye are common in HD patients; these patients should undergo early and frequent eye examinations.