OBJECTIVE: To analyze the clinical characteristics and outcomes of multiple myeloma (MM) patients infected with Listeria monocytogenes (LM) in novel agent era, so as to improve clinicians' understanding. METHODS: Clinical data of 4 MM patients infected with LM in Beijing Chao-yang Hospital from October 2018 to October 2022 was analyzed retrospectively. RESULTS: The average age of the 4 patients was (57.5±4.1) years old. All the patients did not reach deep remission from induction therapy or experienced multiple recurrences of MM, with significant decreased immunoglobulin levels and lymphocyte counts. The initial clinical manifestation was all fever. Three patients developed nervous system symptoms 2-3 days after onset and cerebrospinal fluid examination indicated meningitis. The sensitive anti-infection agents were given according to pathogenic test results 4-5 days after onset. After treatment, two patients recovered, one patient gave up treatment and died after discharged from hospital, and one critical patient died despite exposure to sensitive antibiotics. CONCLUSION MM patients, with the application of novel agents, may have increased risk of LM infection, even critical cases. LM prevention and prompt therapy in early stage for suspected patients is key to reducing the risk of severe infection and mortality.
Humans ; Multiple Myeloma/drug therapy* ; Middle Aged ; Retrospective Studies ; Listeriosis/complications* ; Listeria monocytogenes ; Anti-Bacterial Agents/therapeutic use* ; Male ; Female ; Aged

OBJECTIVE: To study the clinical effects of pomalidomide-based regimen in the treatment of relapsed and refractory multiple myeloma (RRMM). METHODS: 60 patients with RRMM in hematology department of the First Affiliated Hospital of Xinxiang Medical University from November 2020 to January 2023 were selected. Among them, 15 cases were treated with PDD regimen (pomalidomide + daratumumab + dexamethasone), and 45 cases were treated with PCD regimen (pomalidomide + cyclophosphamide + dexamethasone). The clinical effects were evaluated. RESULTS: The median number of treatment cycles for the entire cohort was 5 (2-11), with an overall response rate (ORR) of 75.0%. The ORR of patients treated with PDD regimen was 73.3%, while the ORR of patients treated with PCD regimen was 75.6%. The ORR of 46 patients with non high-risk cytogenetic abnormalities (non-HRCA) was 86.9%, significantly higher than the 35.7% of 14 patients with HRCA (χ² =15.031, P < 0.05). The median PFS for all patients was 8.0(95%CI : 6.8-9.1) months and the median OS was 14.0 (95%CI : 11.3-16.7) months. Among patients treated with PDD regimen, the PFS and OS of patients with non-HRCA were significantly higher than those of patients with HRCA [PFS: 7.0(95%CI : 4.6-9.3) months vs 4.0(95%CI : 3.1-4.8) months, χ² =5.120, P < 0.05; OS: not reached vs 6.0(95%CI : 1.1-10.9) months, χ² =9.870, P < 0.05]. Among patients treated with PCD regimen, the PFS and OS of patients with non-HRCA were significantly higher than those of patients with HRCA [PFS: 9.0(95%CI : 6.2-11.8) months vs 6.0(95%CI : 5.4-6.6) months, χ²=14.396, P < 0.05; OS: not reached vs 11.0(95%CI : 6.4-15.6) months, χ² =7.471, P < 0.05]. CONCLUSION The pomalidomide-based regimen has a good clinical effect and safety in the treatment of RRMM.
Humans ; Multiple Myeloma/drug therapy* ; Thalidomide/administration & dosage* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Female ; Male ; Middle Aged ; Recurrence ; Aged ; Cyclophosphamide/therapeutic use* ; Treatment Outcome ; Antibodies, Monoclonal

OBJECTIVE: To investigate the efficacy and safety of pomalidomide in the treatment of multiple myeloma (MM) with extramedullary disease (EMD). METHODS: The clinical data of 40 pomalidomide-based multiple myeloma patients with extramedullary disease admitted to the Department of Hematology, the First Affiliated Hospital of Bengbu Medical College from February 2019 to August 2023 were retrospectively analyzed. RESULTS: Among the 40 patients, 8 were newly diagnosed with EMD and 32 were refractory/relapsed EMD. There were 21 cases with bone-related extramedullary disease (EM-B) and 19 cases with soft tissue-related extramedullary disease (EM-S). Compared with the EM-B group, the EM-S group exhibited lower LDH levels, an elevation in LDH and a shorter progression-free survival(PFS) (11 months vs 21.5 months, P =0.0363). 32 patients completed 3 courses of treatment, and the short-term efficacy was evaluated. There was no significant difference in the rate of use of 3 or more drugs and ASCT treatment between NDMM group and RRMM group (87.50% vs 93.75%, P >0.05; 25.00% vs 15.63%, P >0.05). Compared with the RRMM group, the overall response rate (ORR) of the NDMM patients was significantly higher (83.33% vs 57.70%, P < 0.05). The deep remission rate (VGPR+CR) of the NDMM group was better than that of the RRMM group (50.00% vs 29.62%, P < 0.05), and the non-response rate (SD+PD) of the NDMM group was significantly lower than that of the R/RMM group (33.33% vs 65.38%, P < 0.05), while the partial remission rate (PR) and mortality rate of the NDMM were not significantly different from those of the RRMM group(P >0.05). With a median follow-up of 26 months, the median PFS was 19 months. Univariate analysis showed that EM-S, high-risk genetic abnormalities, induction therapy did not achieve partial response(PR) or better, and more than 2 lines of treatment failure were associated with shorter PFS. Multivariate analysis showed that the best response to induction therapy did not achieve PR or better, EM-S were an independent adverses prognostic factor for PFS. The results of safety analysis showed that 16 cases had hematological adverse events, including 3 cases of grade 3/4 and 13 cases of grade 1/2. The most common non-hematological adverse events were nausea, vomiting, fatigue and abdominal distension, which were mild and tolerable. CONCLUSION Pomalidomide-based chemotherapy is effective and well tolerated in MM patients with extramedullary disease.
Humans ; Multiple Myeloma/drug therapy* ; Thalidomide/therapeutic use* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Aged ; Treatment Outcome ; Adult

OBJECTIVE: To investigate the efficacy and safety of combination regimen containing daratumumab in multiple myeloma (MM) patients. METHODS: The clinical data of 14 newly diagnosed MM patients and 58 relapsed refractory MM patients treated with combination regimen containing daratumumab from November 2020 to March 2023 in the First Affiliated Hospital of Nanchang University were retrospectively analyzed. The efficacy and safety of combination regimen were analyzed. RESULTS: The median age of the 72 patients was 62 (38-78) years, including 35 males and 37 females. The overall response rate (ORR) of patients receiving first-line, second-line, and third-line or above treatment was 92.9% (13/14), 68.2% (30/44), and 42.9% (6/14), respectively. The median progression-free survival (PFS) was not reached, 15.4 months, and 9.7 months in three groups, respectively (all P <0.05), while the median overall survival (OS) was all not reached. Among relapsed refractory patients, the ORR of those treated with DVd, DPd and DRd regimen was 50.0% (12/24), 40.0% (4/10) and 100% (10/10), the median PFS was 2.8 months, 10.3 months and not reached, and the median OS was 15.4 months, not reached and not reached, respectively. Furthermore, the PFS and OS in the DRd group were superior to those in the other two groups (all P <0.05). Cox univariate and multivariate analysis showed that lactate dehydrogenase (LDH) ≥250 U/L and extramedullary disease were independent adverse prognostic factors for PFS, and LDH ≥250 U/L was also an independent adverse prognostic factor for OS. Hematologic adverse reactions were mainly lymphopenia (87.5%) and thrombocytopenia (52.8%), while non-hematologic adverse reactions were mainly infusion-related reactions (19.4%) and infections (11.1%). CONCLUSIONS The combination regimens containing daratumumab can be used as first-line treatment for patients with newly diagnosed MM. In patients with relapsed refractory MM, early use of regimens containing daratumumab may improve treatment response rate and prolong PFS. The DRd regimen has better therapeutic response and survival advantages. LDH is an independent prognostic factor affecting PFS and OS in MM patients.
Humans ; Multiple Myeloma/drug therapy* ; Middle Aged ; Aged ; Male ; Female ; Antibodies, Monoclonal/administration & dosage* ; Adult ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome

OBJECTIVE: To investigate the effect of daratumumab, lenalidomide and dexamethasone on quality of life in transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). METHODS: The clinical data of 93 TIE NDMM patients in our hospital from January 2020 to December 2022 were retrospectively analyzed. The patients were divided into D-Rd group (48 cases) and Rd group (45 cases) according to treatment regimen. The patients in Rd group were treated with lenalidomide and dexamethasone, while those in D-Rd group were treated with daratumumab on the basis of Rd group. The QLQ-C30 and EQ-5D VAS scores of the two groups were compared at baseline and after 3, 6 and 12 treatment cycles. The last follow-up date was June 30, 2023, and overall survival (OS) was compared between the two groups. RESULTS: The median follow-up period in the D-Rd group was 21 (7-38) months, and the median OS was 34 months, while that in the Rd group was 16 (5-35) months, and the median OS was 28 months. There was significant difference in OS between the two groups ( P <0.05). After 3, 6 and 12 treatment cycles, the QLQ-C30 score and EQ-5D VAS score of the two groups were significantly improved (all P <0.05). After 3 and 12 treatment cycles, the QLQ-C30 score and EQ-5D VAS score of D-Rd group were significantly higher than those of Rd group (all P <0.05). There were no significant differences in the improvement of QLQ-C30 GHS and pain scores between the two groups of patients with age <75 years and ECOG 0-1 score after 3, 6 and 12 treatment cycles (P >0.05). In D-Rd group of patients with age≥75 years, the improvement of QLQ-C30 GHS scores after 3 and 12 treatment cycles and QLQ-C30 pain scores after 3, 6 and 12 treatment cycles was significantly superior to that in Rd group (all P <0.05). In D-Rd group of patients with ECOG 2 scores, the improvement of QLQ-C30 GHS and pain scores after 3, 6 and 12 treatment cycles was significantly superior to that in Rd group (all P <0.05). CONCLUSION Daratumumab, lenalidomide, and dexamethasone can significantly improve OS in TIE NDMM patients without decrease of quality of life, especially in those with age≥75 years or ECOG 2 scores.
Humans ; Multiple Myeloma/drug therapy* ; Lenalidomide/therapeutic use* ; Quality of Life ; Dexamethasone/therapeutic use* ; Retrospective Studies ; Antibodies, Monoclonal/therapeutic use* ; Female ; Male ; Middle Aged ; Aged ; Stem Cell Transplantation

Multiple myeloma is a common and refractory hematological malignancy for which there is currently no radical treatment, and it is prone to relapse. Patients with relapsed and refractory myeloma have often been previously treated with multiple drugs including proteasome inhibitors and / or immunomodulatory drugs. Therefore, for such patients, the primary goal of treatment is to achieve disease control with acceptable toxicity and maintenance of quality of life. In this paper, the aim is to review the clinical effect of selinexor in treating patients with RRMM. As a novel treatment for RRMM, selinexor has a unique pharmacological mechanism that may further improve the clinical response rate of RRMM patients and enhance patients' quality of life. Although selinexor can cause a series of adverse reactions, most of these adverse reactions can be alleviated or disappear after clinical targeted treatment, and effective preventive measures can also minimize the occurrence of adverse reactions. In conclusion, selinexor has shown broad application prospects in RRMM patients, and further research will be conducted in the future to optimize the treatment regimen of selinexor, so that more RRMM patients can benefit from it.
Humans ; Multiple Myeloma/drug therapy* ; Hydrazines/therapeutic use* ; Triazoles/therapeutic use* ; Quality of Life ; Recurrence

OBJECTIVES: Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells and remains incurable. Patients with primary refractory multiple myeloma (PRMM) show poor response to initial induction therapy. This study aims to develop a machine learning-based model to predict treatment response in newly diagnosed multiple myeloma (NDMM) patients, in order to optimize therapeutic strategies. METHODS: NDMM and post-treatment MM patients hospitalized in the Department of Hematology, Third Xiangya Hospital, Central South University, between August 2022 and July 2023 were enrolled. Post-treatment MM patients were categorized into PRMM patients and treatment-responsive MM (TRMM) patients based on therapeutic efficacy. Serum metabolites were detected and analyzed via metabolomics. Based on the metabolomics analysis results and combined with transcriptomic sequencing data of NDMM patients from databases, differentially expressed amino acid metabolism-related genes (AAMGs) among post-treatment NDMM patients with varying therapeutic outcomes were screened. Using bioinformatics analyses and machine learning algorithms, a predictive model for treatment response in NDMM was constructed and used to identify patients at risk for PRMM. RESULTS: A total of 61 patients were included: 22 NDMM, 23 TRMM, and 16 PRMM patients. Significant differences in metabolite levels were observed among the 3 groups, with differential metabolites mainly enriched in amino acid metabolism pathways. Follow-up data were available for 16 of the 22 NDMM patients, including 12 treatment responders (ND_TR group) and 4 with PRMM (ND_PR group). A total of 23 differential metabolites were identified between these 2 groups: 6 metabolites (e.g., tryptophan) were upregulated and 17 (e.g., citric acid) were downregulated in the ND_TR group. Transcriptomic data from 108 TRMM and 77 PRMM patients were analyzed to identify differentially expressed AAMGs, which were then used to construct a prediction model. The area under the receiver operating characteristic curve (AUC) for the model exceeded 0.8, and AUC values in 3 external validation cohorts were all above 0.7. CONCLUSIONS This study delineated the metabolic alterations in MM patients with different treatment response, suggesting that dysregulated amino acid metabolism may be associated with poor treatment response in PRMM. By integrating metabolomics and transcriptomics, a machine learning-based predictive model was successfully established to forecast treatment response in NDMM patients.
Humans ; Multiple Myeloma/drug therapy* ; Machine Learning ; Male ; Female ; Metabolomics/methods* ; Middle Aged ; Aged ; Treatment Outcome ; Transcriptome ; Computational Biology ; Adult ; Multiomics

OBJECTIVE: To investigate the efficacy and safety of daratumumab in treatment of multiple myeloma (MM) patients with renal impairment (RI). METHODS: The clinical data of 15 MM patients with RI who received daratumumab-based regimen from January 2021 to March 2022 in three centers were retrospectively analyzed. Patients were treated with daratumumab or daratumumab combined with dexamethasone or daratumumab combined with bortezomib and dexamethasone and the curative effect and survival were analyzed. RESULTS: The median age of 15 patients was 64 (ranged 54-82) years old. Six patients were IgG-MM, 2 were IgA-MM,1 was IgD-MM and 6 were light chain MM. Median estinated glomerular filtration rate (eGFR) was 22.48 ml/(min·1.73 M₂). Overall response rate of 11 patients with MM was 91% (≥MR), including 1 case of stringent complete response (sCR), 2 cases of very good partial response (VGPR), 3 cases of partial response (PR) and 4 cases of minor response (MR). The rate of renal response was 60%(9/15), including 4 cases of complete response (CR), 1 case of PR and 4 cases of MR. A median time of optimal renal response was 21 (ranged 7-56) days. With a median follow-up of 3 months, the median progression-free survival and overall survival of all patients were not reached. After treatment with daratumumab-based regimen, grade 1-2 neutropenia was the most common hematological adverse reaction. Non-hematological adverse reactions were mainly infusion-related adverse reactions and infections. CONCLUSION Daratumumab-based regimens have good short-term efficacy and safety in the treatment of multiple myeloma patients with renal impairment.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Multiple Myeloma/drug therapy* ; Retrospective Studies ; Dexamethasone/therapeutic use* ; Antibodies, Monoclonal/therapeutic use* ; Bortezomib/therapeutic use* ; Renal Insufficiency/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

OBJECTIVE: To observe the effects of Guizhi Fuling Capsule (GZFLC) on myeloma cells and explore the mechanisms. METHODS: MM1S and RPMI 8226 cells were co-cultured with different concentrations of serum and the cell experiments were divided into negative (10%, 20% and 40%) groups, GZFLC (10%, 20%, and 40%) groups and a control group. Cell counting kit-8 (CCK-8) assays and flow cytometry were used to detect the viability and apoptosis levels of myeloma cells. The effects on mitochondria were examined by reactive oxygen specie (ROS) and tetrechloro-tetraethylbenzimidazol carbocyanine iodide (JC-1) assays. Western blot was used to detect the expression of B cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), cleaved caspase-3, -9, cytochrome C (Cytc) and apoptotic protease-activating factor 1 (Apaf-1). RPMI 8226 cells (2 × 10⁷) were subcutaneously inoculated into 48 nude mice to study the in vivo antitumor effects of GZFLC. The mice were randomly divided into four groups using a completely randomized design, the high-, medium-, or low-dose GZFLC (840, 420, or 210 mg/kg per day, respectively) or an equal volume of distilled water, administered daily for 15 days. The tumor volume changes in and survival times of the mice in the GZFLC-administered groups and a control group were observed. Cytc and Apaf-1 expression levels were detected by immunohistochemistry. RESULTS: GZFLC drug serum decreased the viability and increased the apoptosis of myeloam cells (P<0.05). In addition, this drug increased the ROS levels and decreased the mitochondrial membrane potential (P<0.01). Western blot showed that the Bcl-2/Bax ratios were decreased in the GZFLC drug serum-treated groups, whereas the expression levels of cleaved caspase-3, -9, Cytc and Apaf-1 were increased (all P<0.01). Over time, the myeloma tumor volumes of the mice in the GZFLC-administered groups decreased, and survival time of the mice in the GZFLC-administered groups were longer than that of the mice in the control group. Immunohistochemical analysis of tumor tissues from the mice in the GZFLC-administered groups revealed that the Cytc and Apaf-1 expression levels were increased (P<0.05). CONCLUSION GZFLC promoted apoptosis of myeloma cells through the mitochondrial apoptosis pathway and significantly reduced the tumor volumes in mice with myeloma, which prolonged the survival times of the mice.
Mice ; Animals ; Caspase 3/metabolism* ; Reactive Oxygen Species/metabolism* ; Wolfiporia ; Multiple Myeloma/drug therapy* ; bcl-2-Associated X Protein/metabolism* ; Mice, Nude ; Apoptosis ; Mitochondria/metabolism*

CUDC-101, an effective and multi-target inhibitor of epidermal growth factor receptor (EGFR), histone deacetylase (HDAC), and human epidermal growth factor receptor 2 (HER2), has been reported to inhibit many kinds of cancers, such as acute promyelocytic leukemia and non-Hodgkin's lymphoma. However, no studies have yet investigated whether CUDC-101 is effective against myeloma. Herein, we proved that CUDC-101 effectively inhibits the proliferation of multiple myeloma (MM) cell lines and induces cell apoptosis in a time- and dose-dependent manner. Moreover, CUDC-101 markedly blocked the signaling pathway of EGFR/phosphoinositide-3-kinase (PI3K) and HDAC, and regulated the cell cycle G2/M arrest. Moreover, we revealed through in vivo experiment that CUDC-101 is a potent anti-myeloma drug. Bortezomib is one of the important drugs in MM treatment, and we investigated whether CUDC-101 has a synergistic or additive effect with bortezomib. The results showed that this drug combination had a synergistic anti-myeloma effect by inducing G2/M phase blockade. Collectively, our findings revealed that CUDC-101 could act on its own or in conjunction with bortezomib, which provides insights into exploring new strategies for MM treatment.
Humans ; Antineoplastic Agents/therapeutic use* ; Apoptosis ; Bortezomib/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; ErbB Receptors/antagonists & inhibitors* ; G2 Phase Cell Cycle Checkpoints ; Histone Deacetylase Inhibitors/pharmacology* ; Histone Deacetylases/metabolism* ; M Cells ; Multiple Myeloma/drug therapy*