[Investigation of the immune profile of multiple myeloma patients achieving long-term survival after autologous stem cell transplantation].

Objective: To identify the characteristics of the bone marrow immune microenvironment associated with long-term survival in multiple myeloma (MM) patients. Methods: In the follow-up cohort of patients with newly diagnosed MM and who received "novel agent induction therapy and subsequent autologous stem cell transplantation and immunomodulator maintenance therapy" in the First Affiliated Hospital of Sun Yat-sen University, a cross-sectional study was carried out between August 2019 and May 2020. Using NanoString technology, the RNA expression of 770 bone marrow immune-related markers was compared between 16 patients who had progression-free survival ≥5 years and 5 patients with progressive disease. Among the 16 patients who achieved long-term survival, 9 achieved persistent minimal residual disease (MRD) negative while the other 7 had persistent positive MRD. The functional scores of each kind of immune cells were calculated based on the expression level of characteristic genes, so as to indirectly obtained the proportion of each immune cell subset. The Mann-Whitney U test and the Kruskal Wallis test were used for statistical analysis. Results: The proportion of neutrophils was significantly higher in long-surviving MM patients than in patients with progressive disease [functional scores, 13.61 (13.33, 14.25) vs. 12.93 (12.58, 13.38); Z=2.31, P=0.021]. Among long-surviving patients, those who were MRD-positive had a significantly greater number of mast cells compared with those who were MRD-negative [functional scores, 7.09 (6.49, 8.57) vs. 6.03 (5.18, 6.69); H=2.18, P=0.029]. Compared with patients with progressive disease, four genes (CTSG, IFIT2, S100B, and CHIT1) were significantly downregulated and six (C4B, TNFRSF17, CD70, IRF4, C2, and GAGE1) were upregulated in long-surviving patients. Among long-surviving patients, only gene CMA1 was significantly upgraded, 10 genes (ISG15, OAS3, MX1, IFIT2, DDX58, SIGLEC1, CXCL10, IL1RN, SERPING and TNFSF10) were significantly downregulated in the MRD-positive group compared with that in the MRD-negative group, the first 5 of which are related to the interferon response pathway. Conclusions: The increased neutrophil and mast cell numbers may be related to long-term survival in MM. Interferon signaling activation may be a key bone marrow immune profiling feature for MRD-negative, long-surviving patients with MM.

[Guideline for the diagnosis and management of multiple myeloma-related renal impairment (2024 version)].

Renal impairment is a common complication of multiple myeloma (MM). All patients with MM should be assessed for the presence and severity of renal impairment. The clinicopathological manifestations of MM-related renal impairment are diverse and complex; accordingly, except for light-chain nephropathy, which can often be diagnosed without biopsy based solely on clinical criteria, a renal biopsy is needed for an accurate diagnosis. Supportive care, such as adequate hydration, is required for all patients with MM-related renal impairment. The guideline provide the principles for dose adjustment of the drugs used for MM with renal impairment, including proteasome inhibitors, immunomodulators, monoclonal antibodies, small molecule inhibitors, and alkylating agents, as well as those used for myeloma bone disease. Autologous stem cell transplantation (ASCT) and chimeric antigen receptor T-cell immunotherapy (CAR-T) are effective in patients with moderate renal impairment and are tolerated by the patients. The Chinese Hematology Association; the Chinese Geriatrics Association, Society of Hematology; and the Chinese Research Hospital Association, Society of Nephrology asked experts to collate information on current progress in clinical research relating to MM with renal impairment. This guideline was developed based on the gathered data combined with the latest international consensus and clinical practice guidelines.

Allogeneic CAR T Cells: Complex Cellular Therapy Designs Test the Limits of Our Preclinical Models.

All chimeric antigen receptor (CAR) T-cell products currently approved by the FDA are autologous, which poses several challenges for widespread use. In this issue, Degagné and colleagues present their preclinical research on creating off-the-shelf CAR T cells for multiple myeloma. They utilized the CRISPR/Cas12a genome editing platform and gene knock-in techniques to eliminate alloreactivity and decrease susceptibility to natural killer (NK)-cell elimination. This work has led to an ongoing phase I trial of off-the-shelf CAR T cells for multiple myeloma treatment. See related article by Degagné et al., p. 462 (2).

Real-world advantage and challenge of post-autologous stem cell transplantation MRD negativity in high-risk patients with double-hit multiple myeloma.

BACKGROUND: Autologous stem-cell transplantation (ASCT) remains a beneficial approach for patients with newly diagnosed multiple myeloma (NDMM) in the age of novel therapeutic agents. Nevertheless, limited real-world data is available to establish criteria for identifying high-risk ASCT patients. METHODS: We analyzed outcomes for 168 NDMM patients who underwent ASCT at our center from December 2015 to December 2022. We investigated the impact of the number of high-risk cytogenetics (HRCA), defined as t(4;14), t(14;16), 1q21 gain/amplification, and del(17p), as well as the post-ASCT minimal residual disease (MRD) status as prognostic indicators. We assessed progression-free survival (PFS) and overall survival (OS), and focused on identifying risk factors. RESULTS: The cohort included 42% of patients (n = 71) with 0 HRCA, 42% (n = 71) with 1 HRCA, and 16% (n = 26) with ≥ 2 HRCA. After a median follow-up of 31 months, the median PFS was 53 months (95% CI, 37-69), and OS was not reached for the entire cohort. Despite similar rates of MRD-negativity post-ASCT, patients with ≥ 2 HRCA, termed "double hit" (DH), had a significantly higher risk of progression/mortality than those with 0 or 1 HRCA. Multivariate analysis highlighted DH (HR 4.103, 95% CI, 2.046-8.231) and MRD positivity post-ASCT (HR 6.557, 95% CI, 3.217-13.366) as adverse prognostic factors for PFS, with DH also linked to inferior OS. As anticipated, DH patients with post-ASCT MRD positivity displayed the poorest prognosis, with a median PFS of 7 months post-ASCT. Meanwhile, DH patients with MRD negativity post-ASCT showed improved prognosis, akin to MRD-negative non-DH patients. It is noteworthy to exercise caution, as DH patients who initially achieved MRD negativity experienced a 41% cumulative loss of that status within one year. CONCLUSIONS: This study strongly advocates integrating DH genetic assessments for eligible ASCT patients and emphasizes the importance of ongoing MRD monitoring, as well as considering MRD-based treatment adaptation for those patients in real-world settings.

[Multiple myeloma with IgH::MYC and multiple extramedullary lesions].

A 41-year-old woman with right shoulder pain was found to have multiple tumors with osteolysis and M-proteinemia. Abnormal plasma cells (CD38+, CD138+, Igλ≫κ) were detected in 1.4% of bone marrow nucleated cells, and G-banding analysis revealed a 46,XX,t (8;14), (q24;q32) karyotype in 4 of 20 cells analyzed. A biopsy specimen from an extramedullary lesion had a packed proliferation of aberrant plasmacytoid cells with positive IgH::MYC fusion signals on fluorescence in situ hybridization. The patient was diagnosed with symptomatic multiple myeloma and treated with the BLd regimen, which significantly reduced M protein levels. Extramedullary lesions were initially reduced, but increased again after four cycles. The lesions disappeared with subsequent EPOCH chemotherapy and radiation, and complete remission was confirmed. The patient was then treated with high-dose chemotherapy with autologous peripheral blood stem cell transplantation. Complete remission was maintained for over one year with lenalidomide maintenance therapy. A solitary IgH::MYC chromosomal translocation is extremely rare in multiple myeloma and may be associated with high tumor proliferative capacity, multiple extramedullary lesions, and poor prognosis. Combined therapeutic modalities with novel and conventional chemotherapy and radiation might be a promising treatment strategy for patients with this type of multiple myeloma.

[Application of the Second Revision of the International Staging System (R2-ISS) in the prognostic assessment of newly diagnosed multiple myeloma].

Objective: To investigate the prognostic value of the Second Revision of the International Staging System (R2-ISS) in patients with newly diagnosed multiple myeloma (NDMM) . Methods: The retrospective study was performed in 326 NDMM patients with immunomodulatory drugs and/or proteasome inhibitors as the first-line treatment attending the Department of Hematology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China, from December 2012 to March 2022. The Kaplan-Meier method was used for the survival analysis, with the Log-rank test comparing the between-group differences and Cox proportional risk regression modeling A multifactorial analysis was performed. Results: ①326 patients were included in the study, 190 of whom were males. The median age was 63 years, and the median followup time was 37 months. R2-ISS can effectively predict prognosis, particularly for R-ISS Ⅱ patients. The median progression-free survival (PFS) time of R2-ISS Ⅰ, R2-ISS Ⅱ, R2-ISS Ⅲ, and R2-ISS Ⅳ was 52, 29, 20, and 15 months (P<0.001), while the median overall survival (OS) time was 91, 60, 44, and 36 months (P<0.001). Multifactor analysis revealed that ISS Ⅱ, ISS Ⅲ, del (17p), t (4;14), 1q+, LDH increased, and age >65 years old were independent negative prognostic factors for OS. ISS Ⅱ, ISS Ⅲ, del (17p), t (4;14), 1q+, and LDH were independent negative prognostic factors for PFS. ②The C-index score of R2-ISS was 0.724, higher than that of R-ISS (0.678), indicating high prediction efficiency. ③The median PFS for 1q+-related double-hit in R2-ISS Ⅲ and Ⅳ were 20, 15 months (P=0.084) and the median OS were 35, 36 months (P=0.786), respectively. In R2-ISS Ⅲ, there were twenty-seven cases of 1q+-related double-hit, sixty-one cases of 1q+ single abnormality, and sixty-eight cases with no 1q+. The median PFS for the three groups were 20, 18, and 21 months (P=0.974), while the median OS was 35, 47, and 56 months (P=0.042), respectively. Adjusting the assignment of 1q+ to 1, the median PFS and OS of different R2-ISS stages differed significantly after regrouping (P<0.001) . Conclusions: The prognostic stratification value of R2-ISS is higher than R-ISS, particularly in the highly heterogeneous R-ISS Ⅱ population. Adjusting the assignment of the 1q+-related double-hit can improve R2-ISS, which should be validated in future studies with multi-center and expanded cases.

[Minimal residual disease assessment and progress in multiple myeloma].

With the rapid iteration of multiple myeloma therapeutics over the last two decades, as well as increasing remission rates and depth of remission in patients, traditional methods for monitoring disease response are insufficient to meet the clinical needs of new drugs. Minimal residual disease (MRD) is a more sensitive test for determining the depth of response, and data from multiple clinical trials and meta-analyses show that a negative MRD correlates with a better prognosis than a traditional complete response. MM is at the forefront of MRD evaluation and treatment. MRD detection methods have been continuously updated. The current MRD assessment has three dimensions: bone marrow-based MRD testing, MRD testing based on images of residual metabolic of focal lesions, and peripheral blood-based MRD testing. The various MRD assessment methods complement one another. The goal of this article is to discuss the currently used MRD assays, the progress, and challenges of MRD in MM, and to provide a reference for clinicians to better use the techniques.

Development of a Multivariable Model to Predict the Need for Bone Marrow Sampling in Persons With Monoclonal Gammopathy of Undetermined Significance : A Cohort Study Nested in a Clinical Trial.

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursor conditions to multiple myeloma and related disorders. Smoldering multiple myeloma is distinguished from MGUS by 10% or greater bone marrow plasma cells (BMPC) on sampling, has a higher risk for progression, and requires specialist management. OBJECTIVE: To develop a multivariable prediction model that predicts the probability that a person with presumed MGUS has 10% or greater BMPC (SMM or worse by bone marrow criteria) to inform the decision to obtain a bone marrow sample and compare its performance to the Mayo Clinic risk stratification model. DESIGN: iStopMM (Iceland Screens, Treats or Prevents Multiple Myeloma), a prospective population-based screening study of MGUS. (ClinicalTrials.gov: NCT03327597). SETTING: Icelandic population of adults aged 40 years or older. PATIENTS: 1043 persons with IgG, IgA, light-chain, and biclonal MGUS detected by screening and an interpretable bone marrow sample. MEASUREMENTS: Monoclonal gammopathy of undetermined significance isotype; monoclonal protein concentration; free light-chain ratio; and total IgG, IgM, and IgA concentrations were used as predictors. Bone marrow plasma cells were categorized as 0% to 4%, 5% to 9%, 10% to 14%, or 15% or greater. RESULTS: The c-statistic for SMM or worse was 0.85 (95% CI, 0.82 to 0.88), and calibration was excellent (intercept, -0.07; slope, 0.95). At a threshold of 10% predicted risk for SMM or worse, sensitivity was 86%, specificity was 67%, positive predictive value was 32%, and negative predictive value was 96%. Compared with the Mayo Clinic model, the net benefit for the decision to refer for sampling was between 0.13 and 0.30 higher over a range of plausible low-risk thresholds. LIMITATION: The prediction model will require external validation. CONCLUSION: This accurate prediction model for SMM or worse was developed in a population-based cohort of persons with presumed MGUS and may be used to defer bone marrow sampling and referral to hematology. PRIMARY FUNDING SOURCE: International Myeloma Foundation and the European Research Council.

Expanding Myeloma Training and Care in Western Kenya Through the ECHO Model: The Pilot Phase.

PURPOSE: Multiple myeloma (MM) in rural western Kenya is characterized by under and late diagnosis with poor long-term outcomes. Inadequate skilled rural health care teams are partly to blame. The Extension for Community Healthcare Outcomes (ECHO) model attempts to bridge this skills gap by linking rural primary/secondary health care teams (spokes) to myeloma experts in a tertiary care center (hub) in a longitudinal training program. METHODS: A hub team comprising myeloma experts and administrators from Moi Teaching and Referral Hospital/Academic Model Providing Access to Healthcare was assembled and spoke sites were recruited from rural health care facilities across western Kenya. A curriculum was developed by incorporating input from spokes on their perceived skills gaps in myeloma. Participants joined sessions remotely through virtual meeting technology. ECHO sessions consisted of a spoke-led case presentation with guided discussion followed by an expert-led lecture. An end-of-program survey was used to evaluate participant satisfaction, knowledge, and practice patterns. RESULTS: A total of eight sessions were conducted between April and November 2021 with a median of 40 attendees per session drawn from diverse health care disciplines. Twenty-four spoke sites were identified from 15 counties across western Kenya. The majority of attendees reported satisfaction with the ECHO program (25 of 29) and improvement in their myeloma knowledge (24 of 29). There were 74 new myeloma diagnoses made at the hub site in 2021, representing a 35% increase from the previous 3-year average despite the COVID-19 pandemic that suppressed health care access globally. RECOMMENDATIONS: The pilot ECHO model was successfully implemented in myeloma training for rural-based health care teams. Key attributes included collaborative curriculum development, interactive case-based bidirectional learning, and multidisciplinary engagement.

Circulating plasma cells as a predictive biomarker in Multiple myeloma: an updated systematic review and meta-analysis.

BACKGROUND: Circulating plasma cells (CPCs) are defined by the presence of peripheral blood clonal plasma cells, which would contribute to the progression and dissemination of multiple myeloma (MM). An increasing number of studies have demonstrated the predictive potential of CPCs in the past few years. Therefore, there is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status. METHODS: The PubMed, Embase, and Cochrane Library databases were screened to determine eligible studies from inception to November 5, 2023. Publications that reported the prognostic value of CPCs in MM patients were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were extracted to pool the results. Subgroup analyses were performed based on region, sample size, cut-off value, detection time, initial treatment, and data type. The association between CPCs level and clinicopathological characteristics, including the International Staging System (ISS), Revised-ISS (R-ISS), and cytogenetic abnormalities were also evaluated. Statistical analyses were conducted using STATA 17.0 software. RESULTS: Twenty-two studies with a total of 5637 myeloma patients were enrolled in the current meta-analysis. The results indicated that myeloma patients with elevated CPCs were expected to have a poor OS (HR = 2.19, 95% CI: 1.81-2.66, p < 0.001) and PFS (HR = 2.45, 95% CI: 1.93-3.12, p < 0.001). Subgroup analyses did not alter the prognostic role of CPCs, regardless of region, sample size, cut-off value, detection time, initial treatment, or data type. Moreover, the increased CPCs were significantly related to advanced tumour stage (ISS III vs. ISS I-II: pooled OR = 2.89, 95% CI: 2.41-3.46, p < 0.001; R-ISS III vs. R-ISS I-II: pooled OR = 3.65, 95% CI: 2.43-5.50, p < 0.001) and high-risk cytogenetics (high-risk vs. standard-risk: OR = 2.22, 95% CI: 1.60-3.08, p < 0.001). CONCLUSION: Our meta-analysis confirmed that the increased number of CPCs had a negative impact on the PFS and OS of MM patients. Therefore, CPCs could be a promising prognostic biomarker that helps with risk stratification and disease monitoring.

There is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status.Our meta-analysis revealed that a high CPCs level was significantly associated with worse OS and PFS in MM patients.CPCs could be a promising predictive biomarker that helps with risk stratification and disease monitoring.

PD-1 downregulation enhances CAR-T cell antitumor efficiency by preserving a cell memory phenotype and reducing exhaustion.

BACKGROUND: Despite the encouraging outcome of chimeric antigen receptor T cell (CAR-T) targeting B cell maturation antigen (BCMA) in managing relapsed or refractory multiple myeloma (RRMM) patients, the therapeutic side effects and dysfunctions of CAR-T cells have limited the efficacy and clinical application of this promising approach. METHODS: In this study, we incorporated a short hairpin RNA cassette targeting PD-1 into a BCMA-CAR with an OX-40 costimulatory domain. The transduced PD-1KD BCMA CAR-T cells were evaluated for surface CAR expression, T-cell proliferation, cytotoxicity, cytokine production, and subsets when they were exposed to a single or repetitive antigen stimulation. Safety and efficacy were initially observed in a phase I clinical trial for RRMM patients. RESULTS: Compared with parental BCMA CAR-T cells, PD-1KD BCMA CAR-T cell therapy showed reduced T-cell exhaustion and increased percentage of memory T cells in vitro. Better antitumor activity in vivo was also observed in PD-1KD BCMA CAR-T group. In the phase I clinical trial of the CAR-T cell therapy for seven RRMM patients, safety and efficacy were initially observed in all seven patients, including four patients (4/7, 57.1%) with at least one extramedullary site and four patients (4/7, 57.1%) with high-risk cytogenetics. The overall response rate was 85.7% (6/7). Four patients had a stringent complete response (sCR), one patient had a CR, one patient had a partial response, and one patient had stable disease. Safety profile was also observed in these patients, with an incidence of manageable mild to moderate cytokine release syndrome and without the occurrence of neurological toxicity. CONCLUSIONS: Our study demonstrates a design concept of CAR-T cells independent of antigen specificity and provides an alternative approach for improving the efficacy of CAR-T cell therapy.

Comparative performance of scFv-based anti-BCMA CAR formats for improved T cell therapy in multiple myeloma.

In multiple myeloma (MM), B cell maturation antigen (BCMA)-directed CAR T cells have emerged as a novel therapy with potential for long-term disease control. Anti-BCMA CAR T cells with a CD8-based transmembrane (TM) and CD137 (41BB) as intracellular costimulatory domain are in routine clinical use. As the CAR construct architecture can differentially impact performance and efficacy, the optimal construction of a BCMA-targeting CAR remains to be elucidated. Here, we hypothesized that varying the constituents of the CAR structure known to impact performance could shed light on how to improve established anti-BCMA CAR constructs. CD8TM.41BBIC-based anti-BCMA CAR vectors with either a long linker or a short linker between the light and heavy scFv chain, CD28TM.41BBIC-based and CD28TM.CD28IC-based anti-BCMA CAR vector systems were used in primary human T cells. MM cell lines were used as target cells. The short linker anti-BCMA CAR demonstrated higher cytokine production, whereas in vitro cytotoxicity, T cell differentiation upon activation and proliferation were superior for the CD28TM.CD28IC-based CAR. While CD28TM.CD28IC-based CAR T cells killed MM cells faster, the persistence of 41BBIC-based constructs was superior in vivo. While CD28 and 41BB costimulation come with different in vitro and in vivo advantages, this did not translate into a superior outcome for either tested model. In conclusion, this study showcases the need to study the influence of different CAR architectures based on an identical scFv individually. It indicates that current scFv-based anti-BCMA CAR with clinical utility may already be at their functional optimum regarding the known structural variations of the scFv linker.

Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment with LCAR-B38M CAR T cells: 5-year follow-up of the LEGEND-2 trial.

BACKGROUND: The autologous anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy LCAR-B38M has been approved for the treatment of relapsed and refractory multiple myeloma in many countries across the world under the name ciltacabtagene autoleucel. LEGEND-2 was the first-in-human trial of LCAR-B38M and yielded deep and durable therapeutic responses. Here, we reported the outcomes in LEGEND-2 after a minimal 5-year follow-up. METHODS: Participants received an average dose of 0.5 × 106 cells/kg LCAR-B38M in split or single unfractionated infusions after cyclophosphamide-based lymphodepletion therapy. Investigator-assessed response, survival, safety and pharmacokinetics were evaluated. RESULTS: Seventy-four participants enrolled and had a median follow-up of 65.4 months. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 21.0% and 49.1%, with progressive flattening of the survival curves over time. Patients with complete response (CR) had longer PFS and OS, with 5-year rates of 28.4% and 65.7%, respectively. Twelve patients (16.2%) remained relapse-free irrespective of baseline high-risk cytogenetic abnormality and all had normal humoral immunity reconstituted. An ongoing CR closely correlated with several prognostic baseline indices including favorable performance status, immunoglobulin G subtype, and absence of extramedullary disease, as well as a combination cyclophosphamide and fludarabine preconditioning strategy. Sixty-two (83.8%) suffered progressive disease (PD) and/or death; however, 61.1% of PD patients could well respond to subsequent therapies, among which, the proteasome inhibitor-based regimens benefited the most. Concerning the safety, hematologic and hepatic function recovery were not significantly different between non-PD and PD/Death groups. A low rate of second primary malignancy (5.4%) and no severe virus infection were observed. The patients who tested positive for COVID-19 merely presented self-limiting symptoms. In addition, a sustainable CAR T population of one case with persistent remission was delineated, which was enriched with indolently proliferative and lowly cytotoxic CD4/CD8 double-negative functional T lymphocytes. CONCLUSIONS: These data, representing the longest follow-up of BCMA-redirected CAR T-cell therapy to date, demonstrate long-term remission and survival with LCAR-B38M for advanced myeloma. TRIAL REGISTRATION: LEGEND-2 was registered under the trial numbers NCT03090659, ChiCTRONH-17012285.

[Effect of Recombinant Human Thrombopoietin on Platelet Reconstitution after Autologous Peripheral Blood Stem Cell Transplantation in Patients with Multiple Myeloma].

OBJECTIVE: To analyze the effect of recombinant human thrombopoietin (rhTPO) on platelet (PLT) reconstitution after autologous peripheral blood stem cell transplantation (APBSCT) in patients with multiple myeloma (MM). METHODS: The clinical data of 147 MM patients who were diagnosed in the First Affiliated Hospital of Soochow University and received APBSCT as the first-line therapy were retrospectively analyzed. According to whether rhTPO was used during APBSCT, the patients were divided into rhTPO group (80 cases) and control group (67 cases). The time of PLT engraftment, blood product infusion requirements, the proportion of patients with PLT recovery to≥50×109/L and≥100×109/L at +14 days and +100 days after transplantation, and adverse reactions including the incidence of bleeding were compared between the two groups. RESULTS: There were no significant differences between the two groups in sex, age, M protein type, PLT count at the initial diagnosis, median duration of induction therapy before APBSCT, and number of CD34+ cells reinfused (all P >0.05). The median time of PLT engraftment in the rhTPO group was 10 (6-14) days, which was shorter than 11 (8-23) days in the control group (P < 0.001). The median PLT transfusion requirement in the rhTPO group during APBSCT was 15(0-50)U, which was less than 20 (0-80)U in the control group (P =0.001). At +14 days after transplantation, the proportions of patients with PLT≥50×109/L in the rhTPO group and the control group were 66.3% and 52.2%, while the proportions of patients with PLT≥100×109/L were 23.8% and 11.9%, respectively, with no significant differences (all P >0.05). At +100 days after transplantation, the proportion of patients with PLT≥50×109/L in rhTPO group and control group was 96.3% and 89.6%, respectively (P >0.05), but the proportion of patients with PLT≥100×109/L in rhTPO group was higher than that in control group (75.0% vs 55.2%, P =0.012). There was no difference in the overall incidence of bleeding events in different locations during period of low PLT level of patients between the two groups. In rhTPO group, the rhTPO administration was well tolerated, and the incidences of abnormal liver and kidney function and infection were similar to those in the control group. CONCLUSION: When MM patients undergo first-line APBSCT, subcutaneous injection of rhTPO can shorten the time of platelet engraftment, reduce the transfusion volume of blood products, and be well tolerated, moreover, more patients have achieve a high level of PLT recovery after transplantation, which is very important for ensuring the safety of APBSCT and maintenance therapy.

[Clinical analysis of 14 patients aged ≤ 50 years with high-risk multiple myeloma treated with allogeneic hematopoietic stem cell transplantation].

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in young patients with high-risk multiple myeloma (HRMM) and analyzed the factors affecting patient prognosis. Methods: In this retrospective study, we analyzed the clinical data of 14 patients with HRMM with cytogenetic abnormalities or high-risk biological factors who underwent allo-HSCT at the Hematopoietic Stem Cell Transplantation Center of the Institute of Hematology & Blood Diseases Hospital between November 2016 and November 2022. Results: There were seven males and seven females included in the study, with a median age of 39.5 (31-50) years at the time of allo-HSCT. The median number of treatment lines before transplantation was 2 (1-6) . Before allo-HSCT, 42.9% (6/14) of the patients did not achieve complete remission, while 35.7% (5/14) of the patients achieved measurable residual disease positivity. After transplantation, all patients were evaluated for their treatment response, and the overall response rate was 100% (14/14) . All 14 patients successfully underwent allo-HSCT, with median engraftment times for neutrophils and platelets of 11 (10-14) days and 13 (9-103) days, respectively. Acute grade Ⅱ-Ⅳ graft-versus-host disease (GVHD) occurred in five patients (35.7%) , and two patients (14.3%) developed moderate-to-severe chronic GVHD. The median follow-up time after allo-HSCT was 18.93 (4.10-72.53) months, with an expected 2-year transplant-related mortality rate of 7.1% (95% CI 0%-21.1%) and an expected 2-year overall survival rate of 92.9% (95% CI 80.3%-100.0%) . Moreover, the expected 1-year and 2-year progression-free survival rates were 92.9% (95% CI 80.3%-100.0%) and 66.0% (95% CI 39.4%-100.0%) , respectively, and the 2-year cumulative incidence of relapse was 28.9% (95% CI 0%-56.7%) . Upfront allo-HSCT following complete remission after induced therapy and the presence of chronic GVHD might be favorable prognostic factors. Conclusion: allo-HSCT is an effective treatment for improving the prognosis of young patients with HRMM.

Complex karyotype determined using conventional cytogenetic analysis is a poor prognostic factor in patients with multiple myeloma.

High-risk cytogenetic abnormalities (HRCAs) influence the prognosis of multiple myeloma (MM). However, additional cytogenetic aberrations can lead to poor outcomes. This study aimed to clarify whether HRCAs and additional chromosomal abnormalities affect MM prognosis. Patients with newly diagnosed MM who were treated with novel agents were retrospectively evaluated. The primary objective was to assess the difference in progression-free survival (PFS) and overall survival (OS) between patients with/without HRCAs and between patients with/without complex karyotype (CK). The secondary objectives were to identify factors affecting PFS/OS and factors related to CK. HRCAs were defined as del(17p), t(4;14), t(14;16), and gain/amplification(1q) assessed using fluorescence in situ hybridization. CK was defined as ≥3 chromosomal abnormalities on G-banding. Among 110 patients, 40 had HRCAs and 15 had CK. In this study, survival durations between patients with/without HRCAs were similar, while the CK group had significantly poorer PFS/OS than the no-CK group (median PFS: 9 vs. 24 months and median OS: 29 vs. 97 months, respectively), and a poor prognostic impact of CK was maintained in patients with HRCAs. In multivariate analysis, CK was correlated with poor PFS/OS (hazard ratio [HR]: 2.39, 95% confidence interval [95% CI]: 1.22-4.66 and HR: 2.66, 95% CI: 1.10-6.45, respectively). Bone marrow plasma cell (BMPC) ≥60% (odds ratio [OR] = 6.40, 95% CI: 1.50-27.2) and Revised International Staging System III (OR = 7.53, 95% CI: 2.09-27.1) were associated with CK. Our study suggests that CK may contribute to the poor prognosis of MM. Aggressive disease status including high BMPC proliferation could be relevant to CK.

Recurrence of solitary plasmacytoma in the liver 10 years after the onset of multiple bone lesions.

A 79-year-old man presented with a history of solitary plasmacytoma in the bone 10 years ago. Chemoradiotherapy was effective, and remission was maintained with intermittent treatment at relapse of the bone lesions. One year after the last treatment, a follow-up computed tomography (CT) scan revealed multiple liver masses, and a liver biopsy revealed plasmacytoma. There was no clonal plasma cell infiltration in the bone marrow, and the final diagnosis was solitary plasmacytomas of the liver. Although liver involvement is known in relapsed refractory multiple myeloma, solitary plasmacytoma in the relapsed stage confined to the liver is rare, and all previous reports have been from the initial presentation. To the best of our knowledge, this is the first recurrent case of solitary plasmacytoma of the liver.

Case Report on a Multidisciplinary Approach to Address Malnutrition and Improve a Patient's Fitness for Treatment.

Approximately 5,700 people are diagnosed with myeloma each year in the UK. The standard of care is to receive an autologous stem cell transplant after completion of induction therapy. There are no specific dietary recommendations for people with myeloma, however they are at risk of malnutrition due to symptoms and side effects of treatments. This report describes the journey of a 73-year-old male diagnosed with immunoglobulin A (IgA) lambda myeloma in April 2021. The patient lost 23% of his body weight during 6 months of systemic anti-cancer treatment (SACT), resulting in postponing his transplant twice due to reduced fitness. This report describes an effective, although late, multidisciplinary intervention which was successful for the patient who managed to reestablish a healthy weight and good quality of life. The patient received his transplant in January 2023. This case highlights two important aspects of patient care that should not be underestimated in dietetic clinical practice: early screening and multidisciplinary collaboration. Monitoring the nutritional status of patients and providing early nutrition support can prevent hospital admissions, treatment delays and reduce the associated costs. Multidisciplinary teamwork can improve patient care and clinical outcomes, and it is fundamental to strengthen communication and collaboration among clinical disciplines.