UNASSIGNED: The treatment landscape of relapsed/refractory multiple myeloma (RRMM) is rapidly evolving in Taiwan. The present study aimed to assess the treatment patterns among RRMM patients in Taiwan.
UNASSIGNED: This retrospective, chart review-based, non-interventional study collected data on RRMM patients (≥20 years old) receiving pomalidomide-based treatment between January 2017 and December 2020 across five sites in Taiwan.
UNASSIGNED: Median age of the study population was 65.6 years. Approximately 75% patients received a doublet regimen and 25% were on a triplet regimen. Disease progression was the most common cause for switching to pomalidomide-based treatments in doublet (71.2%) and triplet (58.3%) groups. Patients in doublet and triplet groups (>80%) received 4 mg pomalidomide as a starting dose. Overall response rate (ORR: 31.5% and 45.8%) and median progression-free survival (PFS: 4.7 and 6.8 months) were reported in the doublet and triplet regimen. Doublet regimen was discontinued mainly due to disease progression or death (78.1%); however, triplet regimen patients mainly terminated their treatment due to reimbursement limitations (29.2%). Healthcare resource utilization (HRU) was comparable between doublet and triplet groups.
UNASSIGNED: In Taiwan, half of RRMM patients received pomalidomide-based triplet regimens. Triplet regimens showed a trend towards better outcomes with longer PFS and higher response rates compared to doublets. Notably, the duration of triplet use is influenced by reimbursement limitations. This study provides insight into RRMM treatment patterns in Taiwan and the findings suggest that triplet regimens may be a better alternative than doublet regimens.

This study describes an unusual case of multiple myeloma that progressed to anaplastic multiple myeloma in the pleural fluid. The Wright-stained cytospin of the pleural fluid showed a predominant population of mononuclear plasma cells with pleomorphic nuclei, characterized by both small and large nuclei, which is typical of anaplastic multiple myeloma. However, there were also more binuclear plasma cells with pleomorphic nuclei. Morphometric analysis showed that the mean nuclear length was 1.9-fold and 2.3-fold higher in the large nuclei compared to the small nuclei for the mononuclear plasma cells and binuclear plasma cells, respectively (p<0.001). The patient received B cell maturation antigen chimeric antigen receptor T cell (CAR-T) therapy for relapsed disease, with a significant reduction of the serum monoclonal paraprotein level at day 51 post-therapy. Pathologists should be aware that pleomorphic binuclear plasma cells can be part of the morphologic spectrum in anaplastic multiple myeloma.

Multiple myeloma (MM) is an incurable hematological malignancy with poor survival. Accumulating evidence reveals that lactylation modification plays a vital role in tumorigenesis. However, research on lactylation-related genes (LRGs) in predicting the prognosis of MM remains limited. Differentially expressed LRGs (DELRGs) between MM and normal samples were investigated from the Gene Expression Omnibus database. Univariate Cox regression and LASSO Cox regression analysis were applied to construct gene signature associated with overall survival. The signature was validated in two external datasets. A nomogram was further constructed and evaluated. Additionally, Enrichment analysis, immune analysis, and drug chemosensitivity analysis between the two groups were investigated. qPCR and immunofluorescence staining were performed to validate the expression and localization of PFN1. CCK-8 and flow cytometry were performed to validate biological function. A total of 9 LRGs (TRIM28, PPIA, SOD1, RRP1B, IARS2, RB1, PFN1, PRCC, and FABP5) were selected to establish the prognostic signature. Kaplan-Meier survival curves showed that high-risk group patients had a remarkably worse prognosis in the training and validation cohorts. A nomogram was constructed based on LRGs signature and clinical characteristics, and showed excellent predictive power by calibration curve and C-index. Moreover, biological pathways, immunologic status, as well as sensitivity to chemotherapy drugs were different between high- and low-risk groups. Additionally, the hub gene PFN1 is highly expressed in MM, knocking down PFN1 induces cell cycle arrest, suppresses cell proliferation and promotes cell apoptosis. In conclusion, our study revealed that LRGs signature is a promising biomarker for MM that can effectively early distinguish high-risk patients and predict prognosis.

We aimed to evaluate if circulating plasma cells (CPC) detected by flow cytometry could add prognostic value of R2-ISS staging. We collected the electronic medical records of 336 newly diagnosed MM patients (NDMM) in our hospital from January 2017 to June 2023. The median overall survival (OS) for patients and R2-ISS stage I-IV were not reached (NR), NR, 58 months and 53 months, respectively. There was no significant difference in OS between patients with stage I and patients with stage II (P = 0.309) or between patients with stage III and patients with stage IV (P = 0.391). All the cases were re-classified according to R2-ISS stage and CPC numbers ≥ 0.05% (CPC high) or<0.05% (CPC low) into four new risk groups: Group 1: R2-ISS stage I + R2-ISS stage II and CPC low, Group 2: R2-ISS stage II and CPC high + R2-ISS stage III and CPC low, Group 3: R2-ISS stage III and CPC high + R2-ISS stage IV and CPC low, Group 4: R2-ISS stage IV and CPC high. The median OS were NR, NR, 57 months and 32 months. OS of Group 1 was significantly longer than that of Group 2 (P = 0.033). OS in Group 2 was significantly longer than that of Group 3 (P = 0.007). OS in Group 3 was significantly longer than that of Group 4 (P = 0.041). R2-ISS staging combined with CPC can improve risk stratification for NDMM patients.

BACKGROUND: Multiple myeloma (MM) is the second most common hematological malignancy with its prevalence increasing. Patients with symptomatic MM can show numerous comorbidities, affecting their quality of life (QoL). Physical activity (PA) may improve QoL but is not a standardized intervention of comprehensive cancer centers (CCCs). Since data on the PA of patients with MM are scarce, we aimed to prospectively assess fitness levels and patients\' motivation to join PA-interventions at our CCC.
METHODS: We generated an exercise questionnaire to interview consecutive patients MM. We prospectively collected data on (a) past and current PA, defined by the World Health Organization (WHO) recommendations, (b) knowledge on exercise effects, (c) exercise motivation, and (d) willingness to participate in PA-interventions. Demographics, comorbidities, response, progression-free survival (PFS), and overall survival (OS) were assessed in 211 symptomatic patients MM.
RESULTS: While our patients were elderly and most showed bone involvement, their PA was similar to healthy individuals. Aerobic PA (≥ 60 minutes/week) was performed by 65%, and 25% exercised ≥ 150 minutes/week. WHO PA recommendations were fulfilled by 17% of patients. No sport activities or complete physical inactivity were observed in 35% and 16%, respectively. Notably, 38% were motivated to join MM-specific sport interventions. Self-reported knowledge of PA-induced benefits for patients cancer was high (82%), but only 27% knew which exercises were safe to perform.
CONCLUSIONS: This study provides an overview of the PA of patients MM. Our results suggest that the PA of patients MM might not be much lower than in the age-matched general population.

Basic research to expand treatment options for multiple myeloma is greatly needed due to the refractory nature of the disease. Histone deacetylase (HDAC) inhibitors, which are epigenetic regulators, are attractive but have limited applications. MicroRNAs (miRNAs), which are also epigenetic regulators, are important molecules that may lead to future therapeutic breakthroughs. In this study, we comprehensively searched for miRNAs that are altered by HDAC inhibitors in myeloma cells. We identified miR-7-5p (miR-7) as a miRNA downregulated by HDAC inhibitors. Transfection of myeloma cell lines with miR-7 suppressed cell proliferation, induced apoptosis, and enhanced the effects of the HDAC inhibitor panobinostat. Expression of miR-7 was downregulated by c-Myc inhibition, but upregulated by bortezomib. Comprehensive examination of miR-7 targets revealed four candidates: SLC6A9, LRRC59, EXOSC2, and PSME3. Among these, we focused on PSME3, an oncogene involved in proteasome capacity in myeloma cells. PSME3 knockdown increases myeloma cell death and panobinostat sensitivity. In conclusion, miR-7, which is downregulated by HDAC inhibitors, is a tumor suppressor that targets PSME3. This miR-7 downregulation may be involved in HDAC inhibitor resistance. In addition, combinations of anti-myeloma drugs that complement changes in miRNA expression should be considered.

OBJECTIVE: Continuous lenalidomide maintenance treatment after autologous stem cell transplantation delivers improvement in progression free and overall survival among newly diagnosed multiple myeloma patients and has been the standard of care in the UK since March 2021. However, there is scant information about its impact on patients\' day-to-day lives. This service evaluation aimed to qualitatively assess patients receiving lenalidomide treatment at a cancer centre in London, in order that the service might better align with needs and expectations of patients.
METHODS: We conducted 20 semi-structured interviews among myeloma patients who were on continuous lenalidomide maintenance treatment at a specialist cancer centre in London. Members of the clinical team identified potentially eligible participants to take part, and convenience sampling was used to select 10 male and 10 female patients, median age of 58 (range, 45-71). The median treatment duration was 11 months (range, 1-60 months). Participants were qualitatively interviewed following the same semi-structured interview guide, which was designed to explore patient experience and insights of lenalidomide. Reflexive thematic analysis was used for data analysis.
RESULTS: Four overarching themes were as follows: (i) lenalidomide: understanding its role and rationale; (ii) reframing the loss of a treatment-free period to a return to normal life; (iii) the reality of being on lenalidomide: balancing hopes with hurdles; (iv) gratitude and grievances: exploring mixed perceptions of care and communication. Results will be used to enhance clinical services by tailoring communication to better meet patients\' preferences when making treatment decisions.
CONCLUSIONS: This study highlights that most patients feel gratitude for being offered continuous lenalidomide and perceive it as alleviating some fears concerning relapse. It reveals variations in side effects in different age groups; younger patients reported no/negligible side effects, whilst several older patients with comorbidities described significant symptom burden, occasionally leading to treatment discontinuation which caused distress at the perceived loss of prolonged remission. Future research should prioritise understanding the unique needs of younger patients living with multiple myeloma.

Somatic mutations and polymorphisms may play a role in multiple myeloma (MM) susceptibility and survival. One of the immune checkpoint inhibitors is P-selectin glycoprotein ligand-1 (PSGL-1); the majority of tumor-infiltrating leukocytes express PSGL-1, causing T cell and immune inhibition via PSGL-1 mediator molecules. We aimed to investigate the effect of variable number of tandem repeat (VNTR) polymorphism in the second exon of the PSGL-1 gene on MM susceptibility, response to treatment and survival in our patient group. A total of 238 patients diagnosed with MM between January 2010 and January 2021 and 162 healthy individuals as a control group were included in this cross-sectional study. The genotypes of the VNTR polymorphism in the second exon of the PSGL-1 gene were statistically compared between patients and healthy controls; the statistically significant effects of the genotypes on response to first-line treatment and survival were examined. The AC genotype was significantly higher in healthy controls compared to patients diagnosed with MM (p < 0.001). The median PFS in patients with AA/AB/AC was 56 months, while it was 100 months in patients with BB/CC. The hazard ratio of 1.34 for PFS was found to be clinically significant and having the BB/CC genotype could provide a longer PFS compared to others, but it was not statistically significant due to the sample size. Our study results will shed light on new study plans in terms of immune checkpoint target therapies among conventional treatment preferences in MM.

BACKGROUND: Multiple myeloma (MM) immunophenotyping (IPT) and measurable residual disease (MRD) monitoring by flow cytometry is a surrogate for progression-free survival and overall survival in clinical trials. However, plasma cell enumeration is challenging owing to morphological discrepancies and plasma cell (PC) loss during the sample processing.
METHODS: In (n=87) newly diagnosed MM patients, we evaluated the immunophenotype of PCs at baseline, and for a subset of 35 patients MRD at post-induction was quantified and analyzed for association with outcomes and survival. The software Statistical Package for Social Sciences (SPSS), version 16.0 (SPSS Inc., Chicago, IL, USA) was used for all the statistical analysis.
RESULTS: Immunophenotyping showed strong positive expression of CD56 (83%), CD200 (94%), CD38 (92%), and CD117 (91%) and negative/weak expression of CD19 (83%), CD45 (89%), CD27 (74%), and CD81 (90%) respectively. Negative/weak expression of CD19 was significantly associated with age ≥56 years (p<0.048), with lower albumin (<3.4g/dL, p<0.001). Strong positive CD56 expression was significantly associated with the presence of M-protein (p<0.03). Strong positive CD117 expression was significantly associated with lower albumin (p<0.02). Strong positive CD200 expression was significantly associated with a good response (p<0.02). The median (IQR) value of bone marrow (BM)-MRD% was 0.005 (0.002-0.034). We found that there was no significant difference in the correlation, association, and survival outcomes with MRD%.
CONCLUSIONS: This study sheds light on the utility of IPT as an invaluable diagnostic tool in disease management. The findings of this study could be important when it comes to modifying the criteria for high-risk diseases and implementing a risk-adapted first therapy in clinical practice.

Chimeric antigen receptor (CAR)-T cell-based immunotherapy has emerged as a path-breaking strategy for certain hematological malignancies. Assessment of the response to CAR-T therapy using quantitative imaging techniques such as positron emission tomography/computed tomography (PET/CT) has been broadly investigated. However, the definitive role of PET/CT in CAR-T therapy remains to be established. [18F]FDG PET/CT has demonstrated high sensitivity and specificity for differentiating patients with a partial and complete response after CAR-T therapy in lymphoma. The early therapeutic response and immune-related adverse effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome can also be detected on [18F]FDG PET images. In otherwise asymptomatic lymphoma patients with partial response following CAR-T therapy, the only positive findings could be abnormal PET/CT results. In multiple myeloma, a negative [18F]FDG PET/CT after receiving B-cell maturation antigen-directed CAR-T therapy has been associated with a favorable prognosis. In leukemia, [18F]FDG PET/CT can detect extramedullary metastases and treatment responses after therapy. Hence, PET/CT is a valuable imaging tool for patients undergoing CAR-T therapy for pretreatment evaluation, monitoring treatment response, assessing safety, and guiding therapeutic strategies. Developing guidelines with standardized cutoff values for various PET parameters and tumor cell-specific tracers may improve the efficacy and safety of CAR-T therapy.