Newly diagnosed multiple myeloma patients with CD56 expression benefit more from autologous stem cell transplantation.

BACKGROUND: Several studies showed that lack of CD56 expression was a poor prognostic factor for patients with newly diagnosed multiple myeloma (NDMM). However, other studies were not able to confirm the prognostic value of CD56 in NDMM. This study aimed to evaluate the prognostic value of CD56 expression for patients with NDMM who received autologous stem cell transplantation (ASCT). METHODS: We retrospectively analyzed 370 patients with NDMM under 66 years old and the propensity score matching technique was used to reduce the bias between two groups. RESULTS: CD56 expression was observed in 250 (67.6%) patients, and only half of transplant-eligible patients received ASCT for financial and adverse effects concerns after induction therapy. 54.8% (137/250) CD56 positive patients received ASCT; and 47.5% (57/120) CD56 negative patients received ASCT. Univariate and multivariate analyses showed that ASCT was correlated with longer overall survival (OS) (p < 0.001) and progression-free survival (PFS) (p < 0.001) for CD56 positive patients. However, ASCT had no impact on OS and PFS in univariate and multivariate analysis (p > 0.05). In the propensity score matching analysis, 186 CD56 positive patients were identified, 93 patients had received ASCT and 93 patients had no ASCT. Among 120 CD56 negative patients, 80 patients, 40 in each group, were identified. Among 186 matched CD56 positive patients, patients with ASCT had longer OS (87.6 vs.56.1 months, p = 0.049) and PFS (36.7 vs.30.9 months, p = 0.040). However, ASCT had no impact on OS and PFS for matched CD56 negative patients (p > 0.05). CONCLUSIONS: These results demonstrated that ASCT may improve OS and PFS of CD56 positive patients and had no impact on survival of CD56 negative patients.

Serum exosomal microRNAs as novel biomarkers for multiple myeloma.

Accumulating studies have focused on circulating microRNAs, which might be potential biomarkers for different malignancies. The aim of this study was to investigate the potential of serum exosomal microRNAs to be novel serum biomarkers for smouldering myeloma (SMM) or even multiple myeloma (MM). The levels of serum exosomal microRNAs and serum circulating microRNAs were measured in healthy individuals and patients with SMM (n = 20) or MM (n = 20). Serum exosomal microRNAs and serum circulating microRNAs were extracted from serum, and the expression levels of selected microRNAs were quantified by real-time polymerase chain reaction (PCR). The levels of serum exosome-derived miR-20a-5p, miR-103a-3p, and miR-4505 were significantly different among patients with MM, patients with SMM, and healthy individuals, while there were differences in the levels of let-7c-5p, miR-185-5p, and miR-4741 in patients with MM relative to those in SMM patients or healthy controls. Additionally, a significant correlation was rarely found between the levels of serum and exosomal microRNAs. This study shows that serum exosomal microRNAs can be used independently as novel serum biomarkers for MM.

A Report of 134 Newly Diagnosed Multiple Myeloma Patients with Renal Impairment.

To analyze the effects of bortezomib on the prognosis of the newly diagnosed multiple myeloma patients with renal impairment, we assessed the outcomes of 134 multiple myeloma patients with renal impairment (serum creatinine ≥178 µmol/l) who were treated at Beijing Chaoyang Hospital. The patients were divided into two groups: bortezomib (n = 83) and nonbortezomib (n = 51). The overall response rate of the bortezomib group was higher than that of the nonbortezomib group. There was no significant difference in the time to restore renal function, but the complete renal response ratio was significantly higher in the bortezomib group. The 2-year overall survival (OS) rate of the bortezomib group was significantly greater than the nonbortezomib group, as was the 3-year OS rate. Kaplan-Meier analysis revealed significantly better survival for the bortezomib group. The main side effects in the bortezomib group were thrombocytopenia, peripheral neuropathy, infection, and herpes zoster, and there was a low incidence of grades 3 and 4 adverse events. Our findings indicate that bortezomib-based combination chemotherapy can improve the prognosis of the newly diagnosed multiple myeloma patients with renal impairment and should be considered as a first-line therapy.

A multicenter, open-label phase II study of recombinant CPT (Circularly Permuted TRAIL) plus thalidomide in patients with relapsed and refractory multiple myeloma.

Circularly permuted TRAIL (CPT), a recombinant mutant of human Apo2L/TRAIL, is a novel antitumor candidate for multiple myeloma (MM) and other hematologic malignancies. In this phase II study, the safety and efficacy of CPT plus thalidomide was investigated in thalidomide-resistant MM patients. A total of 43 patients were recruited into three CPT plus thalidomide cohorts based on CPT dosage in sequence: 5 mg/kg (n = 11), 8 mg/kg (n = 17), and 10 mg/kg (n = 15). CPT was administered via intravenous infusion on days 1-5, and thalidomide was given orally at 100 mg once daily in each 21-day cycle. The overall response rate (ORR) of 41 efficacy-evaluable patients was 22.0% (2 complete response, 3 near complete response, and 4 partial response). No significant difference in the ORR was observed among the three dose cohorts; however, the ORR tended to be higher with the higher-dose regimen. Median progression-free survival and median duration of response were 6.6 months and 6.1 months, respectively. The most common treatment-related adverse events (TRAEs) were neutropenia (46.5%), leukopenia (41.9%), fever (37.2%), elevated AST (32.6%), and elevated ALT (20.9%). TRAEs of Grade 3-4 were mainly neutropenia (18.6%), anemia (9.3%), elevated AST (7.0%), and leukopenia (4.7%). No significant differences were found in the incidence and severity of TRAEs among the three cohorts. In conclusion, CPT plus thalidomide was well tolerated with no occurrence of dose-limiting toxicities and demonstrated promising antitumor activity in RRMM patients. CPT at 10 mg/kg for 5 days in combination with thalidomide and dexamethason will be studied in the next clinical trial.

Nursing management of treatment-related venous thromboembolism in patients with multiple myeloma.

Objectives: Venous thromboembolism (VTE) is a common complication among patients with newly diagnosed multiple myeloma (NDMM). Therefore, this study aimed to analyze the incidence and risk factors associated with VTE in the current era of thromboprophylaxis and to propose appropriate nursing measures. Methods: A total of 1,539 NDMM patients were retrospectively analyzed. All patients underwent VTE risk assessment and received aspirin or low molecular weight heparin (LMWH) to prevent thrombosis, followed by appropriate care based on their individual thrombosis risk. The incidence of VTE and its related risk factors were then analyzed. Results: All patients received at least four cycles of therapy containing immunomodulators (IMiDs) and/or proteasome inhibitors (PIs). We assigned 371 patients (24.1%) to the moderate-risk thrombosis group, who received daily aspirin (75 mg) for thrombosis prevention and 1,168 patients (75.9%) to the high-risk group, who received daily low molecular weight heparin (3,000 IU) for thrombosis prevention two times a day. Among all the patients, 53 (3.4%) experienced lower extremity venous thromboembolism events, with three of those patients experiencing a concurrent pulmonary embolism. A multivariate analysis indicated that bed rest lasting more than 2 months and plasma cells of ≥60% were independent factors associated with thrombosis. Conclusion: More effective risk assessment models are needed to predict thrombosis accurately. In addition, nurses involved in the treatment and management of thrombosis should continually engage in professional development to enhance their knowledge and skills.

Prognostic value of t(4;14) translocation in newly diagnosed multiple myeloma patients in novel agent era.

OBJECTIVE: To evaluate the prognostic value of t(4; 14) translocation for newly diagnosed multiple myeloma (MM) patients in the novel agent era. METHODS: We retrospectively analyzed 606 newly diagnosed MM patients treated with novel agents. The propensity score matching technique was used to reduce the bias between groups. RESULTS: Among 606 patients, t(4; 14) was observed in 108 (17.8%) patients, among which 79 (73.1%) were accompanied by 1q21 gain and/or del 17p. Median overall survival (OS) (56.2 vs. 87.3 months) and progression-free survival (PFS) (25.7 vs. 37.6 months) were significantly shorter in patients with t(4;14) compared with patients without cytogenetic abnormalities. Univariate Cox proportional hazards regression analysis showed that the t(4;14) was not associated with shorter OS (p = 0.666) and PFS (p = 0.164). The multivariable analysis also showed t(4;14) was not a poor prognostic factor for OS and PFS of patients with newly diagnosed MM (p > 0.05). After balancing the distribution of factors between patients with and without t(4;14) by the propensity score matching technique, patients with t(4;14) had similar OS (57.6 vs. 56.5 months, p = 0.964) and PFS (26.5 vs. 28.1 months, p = 0.740) with the patients without t(4;14). CONCLUSIONS: These results demonstrated that t(4; 14) alone may be not a poor prognostic factor patients with newly diagnosed MM in the novel agent era.

Characteristics and Risk Factors of Ultra-High-Risk Patients with Newly Diagnosed Multiple Myeloma.

OBJECTIVE: To investigate the clinical characteristics and risk factors of ultra-high-risk (UHR) patients with newly diagnosed multiple myeloma (MM). METHODS: We screened UHR patients with a survival of less than 24 months and we selected patients with a concurrent survival of more than 24 months as a control group. We retrospectively analyzed the clinical characteristics of UHR patients with newly diagnosed MM and screened related risk factors. RESULTS: In total we analyzed 477 patients, which included 121 (25.4%) UHR patients and 356 (74.6%) control patients. Median overall survival (OS) and progression-free survival (PFS) of UHR patients was 10.5 months (7.5-13.5 months) and 6.3 months (5.4-7.2 months), respectively. Univariate logistic regression analysis showed that age > 65 years, hemoglobin (HGB) < 100 g/L, lactate dehydrogenase (LDH) > 250 U/L, serum creatinine (SCr) > 2 mg/dL, corrected serum calcium (CsCa) > 2.75 mmol/L, B-type natriuretic peptide (BNP) or N-terminal prohormone BNP (NT-proBNP) > 2 upper limit of normal (ULN), high-risk cytogenetics, Barthel index score, and International Staging System (ISS) stage III were associated with UHR MM. In a multivariate analysis, age > 65 years, LDH > 250 U/L, CsCa > 2.75 mmol/L, BNP or NT-proBNP > 2 ULN, high-risk cytogenetics, and Barthel index score were independent risk factors for UHR MM. Moreover, UHR patients had a worse response rate than control patients. CONCLUSION: Our study highlighted the characteristics of UHR MM patients and suggested that the combination of organ insufficiency and highly malignant myeloma cells resulted in poor outcomes of patients with UHR MM.

Impact of dialysis dependence on survival for multiple myeloma with renal impairment: a multicenter study in China.

Renal impairment (RI) is a very common complication of multiple myeloma (MM) with a negative impact on survival. Herein we retrospectively analyzed 334 MM patients with renal impairment at diagnosis from three hospitals in China. All 334 patients were divided into three groups, including dialysis dependence (n=43), dialysis independence (n=42), and without dialysis (n=249). Compared with dialysis independence and without dialysis groups, dialysis dependence group had the lowest overall hematologic response (48.8% vs. 97.6% vs. 77.1%, P<0.001) and overall renal response (0.0% vs. 97.6% vs. 72.7%, P<0.001), as well as the highest early mortality within 24 months (50.0% vs. 24.4% vs. 26.3%, P=0.006). Dialysis dependence group had similar progression-free survival (24 vs. 26 vs. 27 months, P=0.231) and significantly shorter overall survival (25 vs. 69 vs. 45 months, P=0.001). Dialysis dependence was independently associated with high mortality within 24 months and shorter overall survival. In conclusion, MM patients with dialysis dependence still tend to suffer a dismal disease course, including a high probability to suffer early mortality, worse hematological and renal response, as well as shorter survival. Dialysis independence could be very promising for survival improvement.

Low Barthel index score is a poor prognostic factor for newly diagnosed multiple myeloma patients.

The basic activities of daily life may affect the prognosis of multiple myeloma (MM) patients and the Barthel index (BI) is currently the most widely used tool to evaluate basic activities of daily life, but few studies have evaluated its prognostic value in MM. We retrospectively enrolled patients with newly diagnosed MM and analyzed the association between the BI and the survival of newly diagnosed MM patients. We totally analyzed 538 patients and found that median overall survival (OS) and progression-free survival (PFS) were significantly shorter in the low BI (≤ 85) group compared with the high BI (> 85) group. Univariate Cox proportional hazards regression analysis showed that the low BI was associated with shorter OS and PFS. It was also confirmed that the low BI was poor prognostic factor for OS and PFS in multivariable analyses. In the propensity score matching analysis, patients with low BI also had shorter OS and PFS. Our study suggested that the low BI was a poor prognostic factor for patients with newly diagnosed MM.

Triplet RVd Induction for Transplant-Eligible Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis.

INTRODUCTION: The combination of lenalidomide, bortezomib, and dexamethasone (RVd) has become standard of care for transplant-eligible patients with newly diagnosed MM (NDMM). This study aimed to determine the efficacy of RVd as induction therapy in terms of response rates and survival outcomes of transplant-eligible patients with NDMM. METHODS: The databases of Medline, Embase, and Cochrane Library were searched until February 1, 2021. Both randomized controlled trials (RCT) and non-RCTs from the available literature were extracted as one-arm data to assess the efficacy of each triplet regimen for the target patients in terms of response rates and survival rates for transplant-eligible patients with NDMM. Data was summarized as estimated pooled value regarding each evaluated index. Risk of bias of studies was assessed with standard methods. RESULTS: The findings of 71 studies published from 2008 to 2020 were analyzed. For RVd induction, the overall response rate (ORR), very good partial response or better (≥ VGPR) rate, and complete response or better (≥ CR) rate after induction were 0.91 (95% CI 0.86-0.95), 0.23 (95% CI 0.17-0.29), and 0.56 (95% CI 0.51-0.61), respectively. Indirect comparisons in efficacy were made between RVd and other traditional triplet regimens. RVd induction led to a better ≥ CR rate than bortezomib, cyclophosphamide, and dexamethasone (VCd) regimen in both postinduction and post-ASCT phase, ≥ CR rate 0.11 (95% CI 0.08-0.15) and 0.21 (95% CI 0.12-0.32), respectively. The 1-year overall survival (OS) rate and 3-year OS rate of RVd regimen were longer than that of bortezomib, thalidomide, and dexamethasone (VTd), 0.97 (95% CI 0.94-0.98) vs 0.71 (95% CI 0.61-0.80), and 0.90 (95% CI 0.79-0.98) vs 0.70 (95% CI 0.64-0.75), respectively. CONCLUSIONS: The RVd induction demonstrated confident response rates and survival benefits for transplant-eligible patients with NDMM.

CD20 expression: A risk stratification factor for newly diagnosed multiple myeloma with t(11;14).

Objective: Translocation (11;14) is one of the most frequent recurrent cytogenetic abnormalities in multiple myeloma (MM), while its clinical prognostic value remains controversial. CD20 expression is uncommon in MM while strongly associated with t(11;14). This study aimed to investigate whether CD20 could provide further prognostic value in MM patients harboring t(11;14). Methods: CD20 expression detected by flow cytometry was retrospectively analyzed in 211 newly diagnosed MM patients with t(11;14). The clinical characteristics and outcomes were analyzed between CD20 positive and negative patients. Results: CD20 expression was found in 34.6% (73/211) newly diagnosed MM (NDMM) patients with t(11;14), associated with lower serum creatine levels and lower incidence of plasmacytoma. Based on similar treatment regimens, CD20 positive patients had a comparable overall response rate to CD20 negative patients, whereas had a lower CR/sCR (complete response/stringent complete response) rate than the latter (31.4% vs. 46.4%, P =0.045). Nevertheless, CD20 positive patients had a longer tendency of progression-free survival (PFS) (59.0 vs. 29.0 months, P =0.163) and significantly longer overall survival (OS) (99.0 vs. 56.0 months, P=0.003) than CD20 negative patients. Further investigation among CD20 expression proportion showed that strong expression of CD20 (>80% of bone marrow plasma cells) exhibited the longest OS (median not reached, P =0.011). However, the favorable impact of CD20 expression on survival was eliminated with the contaminant presence of cytogenetic abnormalities besides t(11;14). Autologous stem cell transplantation (ASCT) could improve the prognosis of CD20 negative t(11;14) patients. Multivariate analysis confirmed that CD20 expression was an independent favorable indicator for longer OS in t(11;14) MM patients. Conclusion: CD20 expression is a favorable prognostic factor in NDMM with t(11;14) and could provide further risk-stratification value in this heterogeneous disease subgroup.

Echocardiography-defined pulmonary hypertension is an adverse prognostic factor for newly diagnosed multiple myeloma patients.

BACKGROUND: Pulmonary hypertension (PH) is a common but rarely recognized comorbidity of multiple myeloma (MM) patients, while its prognostic significance for MM has been rarely reported. METHODS: We retrospectively analyzed the clinical characteristics and prognostic value of baseline echocardiography-defined PH in 426 newly diagnosed MM (NDMM) patients. RESULTS: Echocardiograph-defined PH was found in 12.7% (54/426) of NDMM patients, associated with older age, anemia, and renal insufficiency, as well as severe diastolic dysfunction and higher BNP and NT-pro-BNP levels. Patients with PH presented with a higher prevalence of atrial fibrillation, while with a similar incidence of thrombosis compared with those without PH. Based on similar treatment regimens and autologous stem cell transplantation (ASCT) rates, patients without PH have deeper and better responses than those with PH (p = 0.002). With the remission of MM, 81.5% of PH was reversible, accompanied by improvement of right ventricular dysfunction and normalization of BNP/NT-pro-BNP levels, while could reoccur at MM relapse. Survival analysis revealed that PH was an adverse prognostic factor, associated with reduced progression-free survival (PFS) (21 vs. 50 months, p < 0.001) and overall survival (OS) (45 vs. 90 months, p = 0.014). Multivariate analysis further verified that baseline PH was an independent predictor for shorter PFS and OS. CONCLUSION: In conclusion, echocardiography-defined PH is an adverse prognostic indicator for MM patients and should be routinely evaluated in MM patients at diagnosis to make a precise prognosis.

Cyclopamine sensitizes multiple myeloma cells to circularly permuted TRAIL-induced apoptosis.

Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a promising anti-myeloma drug prototype. The aim of the present study was to investigate the synergistic effects of cyclopamine and circularly permuted TRAIL (CPT) on the proliferation and apoptosis of multiple myeloma cells. The results showed that the inhibitory effects of cyclopamine on the proliferation of human myeloma RPMI-8226 and SKO-007 cells were weak. RPMI-8226 cells were sensitive to CPT; however, the proliferation of SKO-007 cells was not effectively inhibited by CPT. SKO-007 cells were thus considered resistant to cyclopamine and CPT and used for subsequent experiments. Treatment with a combination of cyclopamine and CPT significantly inhibited cell proliferation. Moreover, the Q value showed that cyclopamine combined with CPT could synergistically inhibit the proliferation of SKO-007 cells. Cyclopamine increased CPT-induced apoptosis in the SKO-007 cells and exhibited a synergistic induction of apoptosis when combined with CPT. Moreover, the combination of cyclopamine and CPT decreased the ratio of myeloma stem cells. Quantitative PCR showed that cyclopamine decreased the mRNA expression levels of GLI1/GLI2/GLI3 and increased the expression levels of death receptor 4. In conclusion, the present study showed that a combination of cyclopamine and CPT exhibited synergistic effects on the inhibition of proliferation and induction of apoptosis in myeloma cells.

At least two high-risk cytogenetic abnormalities indicate the inferior outcomes for newly diagnosed multiple myeloma patients: a real-world study in China.

We retrospectively studied the impact of cytogenetic abnormalities in 328 consecutive newly diagnosed multiple myeloma (MM) patients. High-risk cytogenetic abnormalities (HRCAs) included del (17p), amp/gain (1q21), t(4;14), and t(14;16). We defined a standard-risk group by the absence of HRCA, an intermediate-risk group with one HRCA, and a high-risk (HiR) group with at least two HRCAs. The HiR group constituted 14.3% of patients and was associated with a median overall survival (OS) of 28.6 months and progression-free survival (PFS) of 14.0 months. Moreover, the HiR group predicted poor outcomes for OS and PFS in multivariate analyses, and bortezomib prolongation to nine cycles could not bring additional benefit to this entity, suggesting the necessity of more effective therapies for these patients. Furthermore, we confirmed the independent prognostic impact of amp 1q21 in this real-world study.

The Prognostic Role of Prothrombin Time and Activated Partial Thromboplastin Time in Patients with Newly Diagnosed Multiple Myeloma.

PURPOSE: To evaluate the prognostic role of prothrombin time (PT) and activated partial thromboplastin time (APTT) for newly diagnosed multiple myeloma (MM). METHODS: We retrospectively analyzed 354 patients with newly diagnosed MM who received primary treatment in our center. The propensity score matching technique was used to reduce the bias between groups. RESULTS: Among 354 patients, lengthened PT or APTT was observed in 154 (43.5%) patients and 200 (56.5%) patients had normal PT and APTT. Patients with lengthened PT or APTT had significantly shorter median overall survival (OS) (37.5 vs. 73.8 months, p < 0.001) and progression-free survival (PFS) (23.1 vs. 31.6 months, p = 0.001) than those with normal PT and APTT. Univariate Cox proportional hazards regression analyses showed that lengthened PT or APTT was associated with shorter OS (HR = 2.100, 95% CI: 1.525-2.893, p < 0.001). Lengthened PT or APTT was also a poor prognostic factor for OS (HR = 3.183, 95% CI: 1.803-5.617, p < 0.001) in multivariable analyses. The poor effect of lengthened PT or APTT on PFS was confirmed in univariate analysis (HR = 1.715, 95% CI: 1.244-2.365, p = 0.001), but it had no impact on PFS in multivariate analysis (p = 0.197). In the propensity score matching analysis, 154 patients, 77 in each group, were identified. Among 154 matched patients, the OS of patients with lengthened PT or APTT was shorter (38.4 vs. 51.0 months, p = 0.030), but PFS was similar (29.0 vs. 35.0 months, p = 0.248). CONCLUSION: These results demonstrated that lengthened PT or APTT was an independent poor prognostic factor for patients with newly diagnosed MM.

Deep and partial immunoparesis is a poor prognostic factor for newly diagnosed multiple myeloma patients.

We retrospectively analyzed immunosuppression status in 287 newly diagnosed multiple myeloma (MM) patients and assessed the prognostic value of immunoparesis on survival. Deep immunoparesis was defined that one of uninvolved immunoglobulins was below 50% the lower limit of normal ranges, partial immunoparesis was defined at least two suppressed uninvolved immunoglobulins. We found that patients with deep and partial immunoparesis had a significantly shorter median overall survival (OS) and progression-free survival (PFS). Moreover, deep and partial immunoparesis was a poor prognostic factor for OS and PFS in univariate and multivariable analyses. To reduce the bias between the groups, we performed a 1:1 propensity score matching technique for analysis and found that patients with deep and partial immunoparesis also had shorter OS and PFS. Our study showed that deep and partial immunoparesis can be defined an independent poor prognostic factor for patients with newly diagnosed MM.

Incidence and Risk Factors of Osteonecrosis of Femoral Head in Multiple Myeloma Patients Undergoing Dexamethasone-Based Regimens.

OBJECTIVES: To investigate the incidence and risk factors for osteonecrosis of femoral head (ONFH) in multiple myeloma (MM) patients undergoing dexamethasone-based regimens (DBRs). METHODS: A retrospective study was conducted in MM patients administered DBRs between December 2012 and April 2015. Demographic, clinical, and laboratory data were extracted to compare between two groups. Incidence of ONFH were calculated and risk factors identified by both univariate and multivariate analysis. RESULTS: The study group comprised 105 patients undergoing DBRs. Seven patients with ONFH after DBRs were classified as the ONFH group, and the other 98 patients without ONFH were included in the non-ONFH group. Incidence of ONFH was 6.7%. Median age of developing ONFH was 51 years (45-64), and the male to female ratio was 6 : 1. A total of 12 femoral heads were involved, including unilateral in 2 patients and bilateral in 5 patients. After the multivariate analysis, four risk factors were confirmed including male, younger age, cumulative dose of dexamethasone, and hyperlipidemia. CONCLUSION: The overall incidence of ONFH in MM patients treated with DBRs is 6.7%, and 4 risk factors are confirmed including male, younger age, cumulative dose of dexamethasone, and hyperlipidemia in our study.

Bortezomib-based Regimens Improve the Outcome of Patients with Primary or Secondary Plasma Cell Leukemia: A Retrospective Cohort Study

Objective: The management experience for plasma cell leukemia (PCL) is still limited by PCL's rare incidence and aggressive course. The goal of this study was to further identify the efficacy of bortezomib-containing regimens for PCL in Chinese patients. Materials and Methods: In this study, 56 consecutive PCL patients [14 primary PCL (pPCL) and 42 secondary PCL (sPCL) cases] were retrospectively enrolled and 42/56 patients received bortezomib-based regimens (BBRs), including 10/14 pPCL and 32/42 sPCL patients. The patients' survival data, clinical information, and safety data were collected and analyzed. Results: In pPCL and sPCL patients, the overall response rate in the bortezomib group was 90.0% and 25.0%, respectively. The median progression-free survival from PCL diagnosis for pPCL and sPCL was 8.3 months vs. 2.9 months (p=0.043) and median overall survival (OS) from PCL diagnosis was 23.3 months vs. 4.0 months. The OS for patients receiving BBRs was significantly longer for both pPCL (8.3 vs. 1.2 months, p=0.002) and sPCL (4.3 vs. 1.1 months, p<0.001). In multivariate COX analysis, BBR treatment [p=0.008, hazard ratio (HR)=0.38, 95% confidence interval (CI)=0.19-0.77] and very good partial response or better (≥VGPR) (p=0.035, HR=0.19, 95% CI=0.04-0.74) were independent predictors of OS for sPCL patients. For pPCL patients, BBR predicted OS (p=0.029, HR=0.056, 95% CI=0.004-0.745) instead of ≥VGPR (p=0.272, HR=3.365, 95% CI=0.38-29.303). Conclusion: It was found that BBRs could significantly improve OS for both pPCL and sPCL patients.

[Correlation of C-MYC Protein, MDSC and Th17 Cells with Pathogenesis of Myeloma in Different Clinical Stages].

OBJECTIVE: To investigate the correlation of C-MYC protein with MDSC, Th17 cells and the pathogenesis of myeloma in different clinical stages. METHODS: A total of 65 patients with multiple myeloma treated in our hospital were selected as MM group, and 30 healthy subjects were selected as control group. The positive expression rate of C-MYC protein in bone marrow tissue, and the ratios of peripheral blood MDSC and Th17 cells were compared among the two groups, and the correlation of C-MYC protein, the ratio of MDSC, Th17 cells with onset of myeloma at different clinical stages, the relationship of the expression of C-MYC protein with the ratio of MDSC/Th17 cells and the clinical parameters of MM was analyzed. Also, the diagnostic value of single diagnosis and combined diagnosis was compared. RESULTS: The positive expression rate of C-MYC protein in bone marrow, the ratio of MDSC and Th17 cells in peripheral blood in MM group were significantly higher than those in normal control group(P＜0.05); the positive expression rate of C-MYC protein, MDSC and Th17 cells in patients at ISS stage Ⅰ, Ⅱ and Ⅲ MM showed an increasing trend (r=0.432, r=0.401, r=0.351); the correlation between the ratio of MDSC, Th17 cells and the positive expression rate of C-MYC protein in MM patients was positive (r=0.415, r=0.417); the area under ROC curve (AUC) of combined diagnosis was significantly larger than that of single index diagnosis (C-MYC protein, MDSC cells, Th17 cells)(P＜0.05). There was no correlation between the expression of C-MYC protein, the proportion of MDSC, Th17 cells and sex or age in MM patients (P＞0.05). CONCLUSION: The positive expression rate of C-MYC protein and the proportion of MDSC and Th17 cells in MM patients significantly increase, which positively correlates with clinical ISS stagin.

Potential Relationship between Clinical Significance and Serum Exosomal miRNAs in Patients with Multiple Myeloma.

This study evaluated the potential relationship between exosomal miRNAs and clinical symptoms in patients with multiple myeloma (MM). Forty-eight newly diagnosed myeloma patients and sixteen normal donors were enrolled in the study. The results showed that the relative expression levels of let-7c-5p, let-7d-5p, miR-140-3p, miR-185-5p, and miR-425-5p in the exosomes of MM patients were significantly lower than those of healthy controls. Furthermore, there were significant differences in the clinical characteristics of myeloma, such as kidney damage, while the expression levels of the same miRNA in exosomes and serum are not correlated. The expression of exosomal miRNA is related to the expression levels of clinical feature-related factors, such as creatinine, ß2-microglobulin, ß-CTX, and IL-6 in serum. Establishing this relationship could contribute to understanding the pathogenesis of MM.