Newly Diagnosed Multiple Myeloma Patients Research Articles

Survival of Patients with Multiple Myeloma Treated with Bortezomib-Based Triplets and Autologous Hematopoietic Stem Cell Transplant As First Line in Latin America

Background In transplant-eligible newly diagnosed multiple myeloma (NDMM), triplet combinations including proteasome-inhibitors and immunomodulators are the backbone of induction therapy before autologous stem cell transplant (ASCT). Post-ASCT maintenance with lenalidomide is the standard of care. This approach yields deep responses and long overall survival. In Latin America (LATAM) there is scarce data about the outcome of bortezomib-based triplets and ASCT. The aim of this study was to evaluate overall survival (OS) in Latin American transplant-eligible NDMM patients induced with bortezomib-based triplets and ASCT. Methods Retrospective international multicenter cohort study. Patients older than 18 years with MM, who received bortezomib-based triplets followed by ASCT as first line, between 2010 and 2022 were analyzed. Data were collected from clinical records in a standardized report form. We analyzed clinical characteristics at diagnosis and frontline therapy outcomes. Descriptive statistics were performed. Comparisons of characteristics between groups were made using the Chi-square test, Student´s T-test and ANOVA, as appropriate. Survival analysis was performed using Kaplan-Meier curves, comparisons between groups by Log Rank method, and calculations of the risk relationships by Cox regression. Statistical analysis was performed by using IBM SPSS version 25.0. Results A total of 279 patients with NDMM were included, 124 from Argentina, 20 from Chile, 30 from Mexico, 20 from Paraguay, 43 from Peru, 33 from Uruguay, and 9 from Venezuela. Median age was 57 years (range 29-75) with a male predominance (54.8%). Most patients (58%) were treated in private centers. 56.1% were IgG subtype, 24.8% IgA and 17.3% light chain MM. According to the ISS, 69.2% were classified as ISS II or III. Bone disease was the most frequent myeloma-defining events (75.9%), followed by anemia (61.4%), renal failure (24.2%), and hypercalcemia (20.1%). Fluorescence in situ hybridation (FISH) analysis was performed in 53.4% of patients (only 41% with plasma cell sorting), del17p was the most frequent anomaly found (17.4%), followed by t(4;14) (6%), and t(14;16) (2%). The most frequently used induction regimen was cyclophosphamide-bortezomib-dexamethasone (CyBorD) (38.7%), followed by bortezomib-thalidomide-dexamethasone (VTD) (33.7%), and bortezomib-lenalidomide-dexamethasone (VRD) (27.6%). Very good partial remission (VGPR) or better was achieved in 88.3% for VRD, 81.9% for VTD, and 76.8% for CyBorD (p=0.138). Median time from diagnosis to ASCT was 261.5 days. Only 7 patients received tandem ASCT as first-line consolidation. Maintenance treatment was administered to 88.2% of patients and was based on lenalidomide, thalidomide, bortezomib, and lenalidomide+bortezomib in 67.9%, 16.3%, 8.9% and 3.3%, respectively. Treatments and responses are shown in detail in Table 1. With a median follow-up of 45 months (range 7-140), median progression-free survival (PFS) was 33 months (95% CI, 26.7 - 39.3). Median PFS according to treatment was 21 months (95% CI, 14.3 - 27.7) for VRD, 35 months (95% CI, 22.2 - 47.8) for VTD, and 36 months (95% CI, 28 - 44) for CyBorD, p=0.004. Median OS of the whole cohort was not reached (NR), and 86% at 45 months; 75 months for VRD (95% CI, 44 - 106), and NR for CyBorD and VTD (p=0.284) (Figure 1). In the multivariate analysis hypercalcemia (p=0.01) and extramedullary disease (p=0.03) were the only independent risk factors. Discussion FISH was performed only in half of our patients, and the majority without plasma cell sorting. The main used regimen was CyBorD. Although better PFS was obtained with CyBorD, no significant differences in responses or OS were found between VRD, VTD or CyBorD. The reason why VRD PFS and OS were lower merits further study. We report a high rate of maintenance treatment.

Efficacy of D-RVD Vs RVD Among t(11;14) Patients with Newly Diagnosed Myeloma

Introduction: The combination of lenalidomide, bortezomib, and dexamethasone (RVD) is highly effective for newly diagnosed myeloma (NDMM) patients including standard and high risk patients. The addition of daratumumab (dara) to RVD (D-RVD) has been shown to increase deep responses and improve PFS. Phase 3 studies are ongoing to confirm that benefit. We and others have previously demonstrated that patients with t(11;14) have a decreased PFS compared to other standard risk patients. It is unknown whether patients with t(11;14) derive similar benefit from the addition of daratumumab to RVD as part of induction. Here, we present a real-world comparison of consecutively treated patients with t(11;14) with either D-RVD or RVD induction therapy in terms of response and outcomes. Methods: Of the 1000 consecutive NDMM patients treated with RVD between January 2007- August 2016, and 326 NDMM patients treated with D-RVD induction therapy from April 2018 - August 2022, 185 had t(11;14). 121 were in the RVD cohort and 64 were in the D-RVD cohort. Demographic and clinical characteristics and outcomes data were obtained from our institutional review board approved myeloma database and with manual abstraction. Dara was administered as part of standard RVD induction prior to autologous transplant without planned dara during lenalidomide maintenance. Consolidation after transplant was not planned for either cohort. The responses and progression were evaluated per International Myeloma Working Group Uniform Response Criteria. Results: Patient characteristics were similar between the two cohorts. The median age was 63 years old. There were 58.7% and 54.7% males in RVD and D-RVD respectively. There were 45.5% and 36.5% black patients in the RVD and D-RVD cohorts respectively. Patients had free light chain only disease in 27.4% and 32.3%. There were 5.3 and 4% R-ISS stage 3 patients. The VGPR rate or better after induction improved from 49.2 to 81.3 with the addition of dara. After transplant, the VGPR rate or better improved from 76.3 to 94.2% with the addition of dara as part of induction. Median PFS for the RVD cohort is 47.3 months (95% CI 35.9 - 58.8) and not reached in the D-RVD cohort (see Figure 1). The median OS for the RVD cohort is 115 months (95% CI 97-133.2) and not reached with 96.9% of the patients alive at last follow up in the D-RVD cohort. Conclusions: Patients with t(11;14) represent a unique set of myeloma patients with a distinct clinical presentation, biology and response to treatment. These patients have a decreased PFS when compared to other standard risk patient when treated with RVD. Overall survival is similar possibly due to advances in the management of relapsed disease in t(11;14) patients. In this cohort of patients, the addition of dara to RVD improved VGPR rates and PFS. Whether dara is able to completely overcome the PFS disadvantage to t(11;14) will be evaluated with longer follow up.

Carfilzomib, Lenalidomide and Dexamethasone (KRd) As Induction Therapy in High-Risk Newly Diagnosed Multiple Myeloma

Background: Carfilzomib, lenalidomide and dexamethasone (KRd) has been shown to be an effective induction regimen for newly diagnosed myeloma (NDMM), particularly in myeloma with high-risk (HR) features in the FORTE trial (Mina et al, Lancet Onc 2023). Here, we present a retrospective analysis in patients with HR NDMM in a real-world population from two high-volume centers, highlighting efficacy and survival outcomes in high-risk subgroups to gain a better understanding of the utility of this regimen in clinical practice. Methods: We conducted a retrospective study of patients with HR NDMM treated with KRd at Memorial Sloan Kettering (MSK) and Winship Cancer Institute from 1/1/2015 to 9/30/22. Cutoff date for analysis was 12/31/2022. HR was defined as the presence of high-risk cytogenetic abnormalities (HRCA) including +1q, del(1p), t(4;14), t(14;16), t(14;20), and/or del(17p), circulating plasma cells (cPC) ≥5%, extramedullary disease (EMD), and/or complex cytogenetics by conventional cytogenetics. Patients who received ≤1 prior cycle of a different MM regimen were included. Responses and progression were evaluated per International Myeloma Working Group Uniform Response Criteria. Discrete patient characteristics were summarized by frequency (percentage) and continuous characteristics were summarized by median (Interquartile Range, IQR). Progression-free survival (PFS) and overall survival (OS) were evaluated by Kaplan-Meier method. Association between time to event outcomes and patient's characteristics were determined by log-rank test. Univariate Cox proportional hazard model was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Results: We identified 179 consecutive NDMM patients with HR features treated with KRd at MSK (N=106) and Winship Cancer Institute (N=73). Baseline patient characteristics are listed in Table 1. The median age was 62 (IQR, 55-68) and 28% of patients were Black. There were 45 (25%), 76 (42%), 47 (26%), and 11 (6%) patients with 0, 1, 2, 3+ HRCA, respectively. A median of 5 (IQR 4-6) cycles were administered. At data cutoff, 70% of patients received upfront autologous stem cell transplant (ASCT). Best overall response rate (ORR) by the end of KRd induction was 94% for 178 response-evaluable patients, including 39% with ≥complete response (CR) and 78% with ≥very good partial response (VGPR). After a median follow-up of 41.9 (95% CI 39-45.6) months, the median PFS (mPFS) was 78.2 months (95% CI 52.5-not reached [NR]), and 2-year estimated PFS was 79% (73%-85%). Median OS (mOS) was not reached, and 2-year OS was 92% (95%CI 89%-97%). For HR subgroups based on the number of HRCA present, mPFS was 78.2 (95% CI 40.1-NR), 65.2 (43.4-NR), 55.9 (44.9-NR), and 17.5 (8.78-NR) months for patients with 0, 1, 2, 3+ HRCA, respectively, with 2-year PFS of 83% (95% CI, 73%-95%), 82% (74%-92%), 78% (67%-91%), and 46% (24%-87%), respectively (P=0.35). Median OS was NR for patients with 0, 1, and 2 HRCA and was 58.2 months (95% CI 38.8-NR) for patients with 3+ HRCA with 2-year OS of 93% (95% CI, 86%-100%), 96% (91%-100%), 89% (81%-99%), and 81% (60%-100%), respectively (P=0.13). In univariable analysis, lack of t(14;16) (HR 0.32, 95%CI 0.11-0.95; P=0.03), White race (HR 0.38, 95%CI 0.17-0.84; P=0.02), presence of ≤2 HRCA (HR 0.31, 95%CI 0.11-0.92; P=0.04) were associated with longer OS in this cohort of HR-NDMM patients treated with KRd induction. Multivariable analysis for clinical variables, including specific HRCA, number of HRCA present, age, gender, race, R-ISS stage, presence of EMD, presence of cPCs, cardiac history, and upfront ASCT did not demonstrate any single variable was a significant predictor of progression or death. Conclusion: For this real-world patient population, KRd induction was associated with high response rates and promising outcomes with best ORR of 94% and mPFS of 6.5 years for patients with high-risk newly diagnosed multiple myeloma consistent with FORTE trial data. PFS did not significantly differ among HR patients with 0, 1, 2, 3+ HRCA although mPFS for patients with 3+ HRCA was only 17.5 months. Data with maintenance therapy and longer follow-up outcomes will be presented at the meeting.

Progression-Free Survival of Daratumumab Versus Bortezomib Triplet Combination With Lenalidomide and Dexamethasone in Transplant Ineligible Patients With Newly Diagnosed Multiple Myeloma: TAURUS Chart Review Study

BackgroundDaratumumab, lenalidomide and dexamethasone (DRd) and bortezomib, lenalidomide and dexamethasone (VRd) are preferred regimens for transplant ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). Both DRd and VRd demonstrated superior efficacy versus Rd in the MAIA and SWOG S0777 trials, respectively, but there is no head-to-head (H2H) clinical trial comparing their efficacy. Differing populations in the MAIA and S0777 trials make an unadjusted comparison of outcomes challenging and biased. The current TAURUS study is the first real-world H2H study comparing progression-free survival (PFS) among TIE NDMM patients treated with DRd or VRd as first-line (1L) in similar clinical settings. Materials and MethodsA multicenter chart review study was conducted at nine sites across the United States. All TIE patients treated with DRd and a randomly selected population of VRd patients were included. TIE NDMM patients aged ≥65 were included if they initiated 1L DRd/VRd between January 2019 and September 2021. PFS was defined as the time from DRd/VRd initiation until disease progression or death. A doubly-robust multivariable Cox regression model combined with inverse probability of treatment weighting (IPTW) methodology was used to compare PFS between cohorts. ResultsWeighted cohorts comprised 91 DRd and 87 VRd patients. Thirteen DRd and 24 VRd patients experienced progression/death. Patients treated with DRd had a lower risk of progression/death versus VRd (adjusted hazard ratio: 0.35, 95% confidence interval: [0.17; 0.73]). ConclusionDRd is associated with a significantly lower risk of disease progression or death compared to VRd as 1L treatment for TIE NDMM patients.

Ixazomib, daratumumab and low-dose dexamethasone in intermediate-fit patients with newly diagnosed multiple myeloma: an open-label phase 2 trial

The outcome of non-transplant eligible newly diagnosed multiple myeloma (NDMM) patients is heterogeneous, partly depending on frailty level. The aim of this study was to prospectively investigate the efficacy and safety of Ixazomib-Daratumumab-low-dose dexamethasone (Ixa-Dara-dex) in NDMM intermediate-fit patients. In this phase II multicenter HOVON-143 study, IMWG Frailty index based intermediate-fit patients, were treated with 9 induction cycles of Ixa-Dara-dex, followed by maintenance with ID for a maximum of 2 years. The primary endpoint was overall response rate on induction treatment. Patients were included from October 2017 until May 2019. Trial Registration Number: NTR6297. Sixty-five patients were included. Induction therapy resulted in an overall response rate of 71%. Early mortality was 1.5%. At a median follow-up of 41.0 months, median progression-free survival (PFS) was 18.2 months and 3-year overall survival 83%. Discontinuation of therapy occurred in 77% of patients, 49% due to progression, 9% due to toxicity, 8% due to incompliance, 3% due to sudden death and 8% due to other reasons. Dose modifications of ixazomib were required frequently (37% and 53% of patients during induction and maintenance, respectively), mainly due to, often low grade, polyneuropathy. During maintenance 23% of patients received daratumumab alone. Global quality of life (QoL) improved significantly and was clinically relevant, which persisted during maintenance treatment. Ixazomib-Daratumumab-low-dose dexamethasone as first line treatment in intermediate-fit NDMM patients is safe and improves global QoL. However, efficacy was limited, partly explained by ixazomib-induced toxicity, hampering long term tolerability of this 3-drug regimen. This highlights the need for more efficacious and tolerable regimens improving the outcome in vulnerable intermediate-fit patients. Janssen Pharmaceuticals, Takeda Pharmaceutical Company Limited.

Lenalidomide plus Dexamethasone Combination as First-Line Oral Therapy of Multiple Myeloma Patients: A Unicentric Real-Life Study.

Based on the results obtained in clinical trials, the use of the combination of lenalidomide and dexamethasone (Len/Dex) has become a potential therapeutic choice for newly diagnosed multiple myeloma (NDMM) ineligible for autologous stem cell transplantation. This study evaluated 89 frail NDMM patients treated with first-line oral association. At the last follow-up, 34 out of 89 patients (38.2%) were alive, and 22 were still in treatment with Len/Dex. Among 73 evaluable patients who received at least two cycles, the overall response rate was 71% (N = 52). The disease control rate, defined as any level of clinical response to therapy, occurred in 71 patients (97%). We reported one or more adverse events of grade 3 or 4 (G3/4) in 65.2% (N = 58) of patients, with a prevalence of hematological toxicity (24 patients), leading to an overall discontinuation of treatment in two cases. In univariate analysis, high ISS, high serum β2-microglobulin, and creatinine clearance <30 mL/min negatively impact OS, while the depth of response positively impacts OS. Moreover, G3-4 anemia, ISS, frailty score, and ECOG negatively impacts PFS. In conclusion, elderly and more frail patients benefit from the Len/Dex combination also in the era of monoclonal antibodies, ensuring an increased PFS and OS in patients where the therapeutic choice is often limited and usually not very effective.

The Leucine-Rich α2-Glycoprotein-1 Levels in Patients with Multiple Myeloma

Introduction: Angiogenesis is considered important in the pathogenesis of multiple myeloma (MM), as well as in the targeted treatment of the disease. Leucine-rich α2-glycoprotein 1 (LRG1) is a protein that participates in angiogenesis and its effect on solid organ tumors has been investigated recently. This study aimed to investigate the relationship between MM and LRG1. Methods: The MM patients who admitted to Hatay Mustafa Kemal University Hematology Clinic between September 2021 and October 2022 were included in the study. The study consists of a total of 4 groups: newly diagnosed MM (NDMM), relapsed refractory MM (RRMM), MM in remission (Rem-MM), and control group. Demographic data were retrieved from hospital records. Blood samples of our study groups were centrifuged at 1,500 × g for 10 min and serum was collected. LRG1, IL-6, IL-8, TGF-β1, HIF-1α, FGF-2, and VEGF levels were analyzed in all groups by ELISA method, and statistical analysis was performed. Results: A total of 112 individuals, including NDMM (n: 27), RRMM (n: 18), Rem-MM (n: 42), and control group (n: 25), were enrolled in the study. Based on the analyses, the NDMM group exhibited significantly elevated levels of LRG1 (p < 0.001), TGF-1 (p < 0.001), and HIF-1α (p = 0.046, p < 0.001, and p = 0.003 compared to the RRMM, Rem-MM, and control groups, respectively) compared to the other groups. LRG1 levels were positively correlated with creatinine (r: 0.363, p = 0.001), calcium (r: 0.344, p = 0.001), total protein (r: 0.473, p < 0.001), erythrocyte sedimentation rate (r: 0.547, p < 0.001), lactate dehydrogenase (r: 0.321, p = 0.003), beta-2-microglobulin (r: 0.312, p = 0.017), IL-6 (r: 0.478, p < 0.001), IL-8 (r: 0.240, p = 0.03), TGF-β1 (r: 0.521, p < 0.001), and HIF-1α (r: 0.321, p = 0.003) levels and were negatively correlated with hemoglobin (r: −0.512, p < 0.001) and albumin (r: −0.549, p < 0.001) levels. Receiver operating characteristics (ROC) analysis revealed the association of LRG1 with the highest AUC value of 0.959 (95% CI: 0.904–1, p < 0.001) and the optimal cut-off value of 534.95 ng/mL (sensitivity: 93% and specificity: 99%) in the NDMM group compared to the control group. Conclusion: In this study, providing data for the first time on LRG1 levels in the setting of MM. LRG1 levels were found to be significantly higher in NDMM patients and in our study discriminate this patient population from RRMM, Rem-MM, and normal controls. Therefore, LRG1 seems to a potential biomarker that should be evaluated in future studies addressing the diagnosis, staging, follow-up, prognosis, and treatment target of MM.

Prognostic value of low muscle mass at the 12th thoracic vertebral level in multiple myeloma treated with transplantation: CAREMM-2101 study.

Autologous hematopoietic stem cell transplantation (ASCT) has been introduced as a standard treatment for newly diagnosed multiple myeloma (NDMM) following novel agent-based induction chemotherapy. This study investigated whether pre-ASCT low muscle mass evaluated using the paraspinal muscle index (PMI) at the 12th thoracic vertebra (T12) level is a reliable prognostic marker in NDMM after chemotherapy. A multi-center registry database was retrospectively analyzed. Between 2009 and 2020, 190 patients with chest computed tomography images underwent frontline ASCT following induction therapy. The PMI was defined as the value of the paraspinal muscle area at the T12 level divided by the square of the patient's height. The cut-off value indicating a low muscle mass was sex-specific, using the lowest quintiles. Of the 190 patients, 38 (20%) were in the low muscle mass group. The low muscle mass group had a lower 4-year overall survival (OS) rate than the non-low muscle mass group (68.5% vs. 81.2%; P = 0.074). The median progression-free survival (PFS) in the low muscle mass group was significantly shorter compared with the non-low muscle mass group (23.3 months vs. 29.2 months; P = 0.029). The cumulative incidence of transplant-related mortality (TRM) was significantly higher in the low muscle mass group than in the non-low muscle mass group (4-year probability of TRM incidence, 10.6% vs. 0.7%; P < 0.001). In contrast, no significant difference in the cumulative incidence of disease progression was found between the two groups. Multivariate analysis revealed that low muscle mass was associated with significant negative outcomes for OS [(hazard ratio (HR): 2.14; P = 0.047], PFS (HR: 1.78; P = 0.012), and TRM (HR: 12.05; P = 0.025). Paraspinal muscle mass may have a prognostic role in NDMM patients who undergo ASCT. Patients with low paraspinal muscle mass have lower survival outcomes compared to non-low muscle mass group.

Dynamics of Bone Disease Biomarkers Dickkopf-1 and Sclerostin in Patients with Multiple Myeloma.

Dickkopf-1 (DKK-1) and sclerostin are essential Wnt/β-catenin pathway inhibitors, playing an important role in multiple myeloma bone disease (MBD). We aimed to examine the serum DKK-1 and sclerostin variations in newly diagnosed multiple myeloma (NDMM) patients at diagnosis and in the course of therapy, including autologous stem cell transplantation (ASCT). This study included 41 NDMM-patients and 33 controls. MBD was assessed by whole-body low-dose computed tomography. DKK-1 and sclerostin were assayed by commercial ELISA kits. At diagnosis, NDMM-patients revealed significantly higher DKK-1 and sclerostin values (p < 0.0001), showing dependence on disease stage (lowest in ISS-I and highest in ISS-III: p < 0.0012 and p < 0.025, respectively, for both proteins). Bone lesions revealed significant positive correlation with both DKK-1 (p < 0.05) and sclerostin (p < 0.0001). In the course of therapy, significant reduction, more prominent after ASCT, was observed for both parameters in each treatment point compared to the baseline (p < 0.0001). Markedly lower sclerostin (p < 0.01) and DKK-1 (p < 0.05) values were observed in patients with complete and very good partial response compared to those with partial response, stable, or progressive disease. Sclerostin and DKK-1 in NDMM patients reflect the MBD severity and the effect of therapy. Both proteins could represent a novel tool for better disease monitoring and effectiveness of therapy.

Regulatory Effect and Mechanism of Erythroblastic Island Macrophages on Anemia in Patients with Newly Diagnosed Multiple Myeloma.

To examine the clinical characteristics and anemia-related factors in patients with newly diagnosed multiple myeloma (NDMM), as well as the effect and mechanism of erythroblastic islands (EBIs) and EBI macrophages in NDMM patients with anemia. We collected and analyzed clinical data to find anemia-related factors. Using flow cytometry, the numbers and ratios of erythroblasts and EBI macrophages were determined. RNA sequencing (RNA-seq) was used to determine the differences of EBI macrophages in NDMM patients with or without anemia. Based on the clinical characteristics of NDMM patients with anemia, MCV, abnormal levels of albumin, osteolytic lesions, and Durie-Salmon (DS) stage are risk factors for anemia. Patients with anemia have fewer erythroblasts, erythroblastic islands (EBIs), and EBI macrophages in their bone marrow than patients without anemia. RNA-seq analysis of EBI macrophages from the bone marrow of patients with and without anemia revealed that macrophages from patients with anemia are impaired and tend to promote the production of interleukin-6, which has been demonstrated to be an essential survival factor of myeloma cells and protects them from apoptosis. In NDMM patients with anemia, EBI macrophages are impaired, which causes anemia in those patients. Our finding highlights the significance of EBI macrophages in anemia in NDMM patients and provides a new strategy for recovery from anemia in these patients.

Bortezomib, Melphalan, and Prednisone With or Without Daratumumab in Transplant-ineligible Asian Patients With Newly Diagnosed Multiple Myeloma: The Phase 3 OCTANS Study.

In the global phase 3 ALCYONE trial, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) improved outcomes versus VMP in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. Here, we report the primary analysis of the phase 3 OCTANS trial of D-VMP versus VMP in transplant-ineligible Asian NDMM patients. In total, 220 patients were randomized (2:1) to receive 9 cycles of VMP (bortezomib 1.3 mg/m2 subcutaneously twice weekly in Cycle 1 and weekly in Cycles 2 to 9; melphalan 9 mg/m2 orally; and prednisone 60 mg/m2 orally on Days 1 to 4 of each cycle) ± daratumumab 16 mg/kg intravenously weekly in Cycle 1, every 3 weeks in Cycles 2 to 9, and every 4 weeks thereafter until disease progression. After a median follow-up of 12.3 months, very good partial response or better rates (primary endpoint) were 74.0% versus 43.2% with D-VMP versus VMP (odds ratio, 3.57; 95% confidence interval [CI], 1.99-6.43; P < .0001). Median progression-free survival (PFS) with D-VMP versus VMP was not reached versus 18.2 months (hazard ratio, .43; 95% CI, .24-.77; P = .0033); 12-month PFS rates were 84.2% versus 64.6%. The most frequent grade 3/4 treatment-emergent adverse events with D-VMP/VMP were thrombocytopenia (46.5%/45.1%), neutropenia (39.6%/50.7%), and leukopenia (31.3%/36.6%). D-VMP demonstrated a favorable benefit/risk profile in transplant-ineligible Asian NDMM patients. This trial was registered at www. gov as #NCT03217812.

A PREDICTIVE MODEL FOR ULTRA‐HIGH RISK IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA: A SINGLE‐CENTER STUDY IN CHINA

Introduction: Although novel therapies have significantly improved the prognosis of multiple myeloma (MM) patients, there are still a subgroup of MM patients experienced early relapse or disease progression. To early identify the patients with compromised prognosis in our center, the study aimed to establish a predictive model for ultra-high risk (UHR) in MM. Methods: A study from a tertiary hospital in western China analyzed the patients with newly diagnosed MM (NDMM) receiving bortezomib and/or lenalidomide-included regimens from January 2015 to June 2021. The last follow-up date was December 31, 2022. The patients were randomly divided (2:1) into training and validation cohorts, and the patients with progression-free survival (PFS) less than 12 months were defined as UHR. Univariate and multivariate Cox regression analyses were performed for clinical feature selection. Independent baseline factors were incorporated and scored to develop the predictive model. The UHR group was then defined beyond the optimal cut-off value of total scores. Results: A total of 314 MM patients were enrolled and 102 (32.5%) patients underwent autologous hemopoietic stem cell transplantation (ASCT). The median time of follow-up was 36.6 months. Disease progression and death occurred in 178 (56.7%) and 69 (22.0%) patients. The median PFS (mPFS) was 36.5 months, and the median overall survival (mOS) was not reached. The mPFS of patients stratified into R-ISS III, R2-ISS III, R2-ISS IV, IMWG high-risk and mSMART double/triple hit was 23.8, 25.6, 10.0, 17.2 and 10.5 months, respectively. Among 54 patients at UHR, less than half of them could be identified by the aboved stratification systems. In the training cohort, elevated LDH, hypercalcemia, 1q21 gain/amplification (1q+) and the presence of extramedullary disease (EMD) showed significant association with UHR in NDMM. Referring to the results, the UHR predictive model was developed as 5 points for elevated LDH, 6 points for hypercalcemia, 7 points for 1q+ and 10 points for EMD. Patients with total scores of more than 12 points can be predicated as UHR. This model identified UHR and non-UHR groups with significantly different mPFS (9.8 v.s. 37.5 months, HR = 3.24, 95% CI:2.09-5.03, P < 0.001) and 5-year OS (63.3% vs. 83.8%, HR = 2.92, 95% CI: 1.47-5.81, P = 0.002). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.77, and in the validation cohort, the UHR model kept good discrimination (AUC: 0.79) at the latest follow-up. Conclusions: In this study, elevated LDH, hypercalcemia, 1q+ and EMD were selected and scored to develop the UHR model for NDMM patients. At present, the extension of follow-up time and expansion of sample size in the validation cohort are still ongoing. External validity is also designed to verify the generalizability of the model. The research was funded by: Natural Science Foundation of Sichuan Province, China, Grant/Award Number: 2022NSFSC1299 Keywords: Risk Models, Multiple Myeloma No conflicts of interests pertinent to the abstract.

More accurate prediction of treatment response than meanapparent diffusion coefficient value in multiple myeloma using whole bodyMRI histogram analysis.

Aim: To assess baseline histogram parameters from apparent diffusion coefficient (ADC) images in predicting early treatment response in newly diagnosedmultiple myeloma (NDMM) patients. Methods: The histogram parameters of lesions in 68 NDMM patients were obtained with the Firevoxel software. The presence of deep response after two cycles of induction was recorded. Results: Some parameters were significantly different between the two groups, for example, ADC 75% in lumbar spine (p=0.026). No significant difference in mean ADC for any anatomic site was found (all p>0.05). The combination of ADC 75, ADC 90and ADC 95% in lumbar spine;ADC skewnessand ADC kurtosis in rib achieved a sensitivity of 100% in predicting deep response. Conclusion: Histogram analysis of ADC images can describe NDMM heterogeneity and accurately predict treatment response.

Risk nomogram for assessing renal recovery in patients with newly diagnosed multiple myeloma-related renal impairment

To determine risk factors affecting renal recovery in newly diagnosed multiple myeloma (NDMM) patients with renal impairment (RI) and establish a risk nomogram. This multi-center, retrospective cohort study included 187 NDMM patients with RI, 127 of whom were admitted to Huashan Hospital and assigned to the training cohort and 60 were admitted to Changzheng Hospital and assigned to the external validation cohort. The baseline data of the 2 cohorts were compared, and survival and renal recovery rates were analyzed. Independent risk factors affecting renal recovery were determined by binary logistic regression analysis, and a risk nomogram was established and subsequently tested in the external validation cohort. Results: The median overall survival (OS) improved in patients who achieved renal recovery etc within 6 courses of MM directed treatment compared with patients without renal recovery. Median time to renal recovery was 2.65 courses, and the cumulative renal recovery rate during the first 3 courses was 75.05%. Involved serum free light chain (sFLC) ratio of >120 at diagnosis, time from renal impairment to treatment > 60 days, and a hematologic response without a very good partial remission (VGPR) or better resulted as independent risk factors for renal recovery during the first 3 courses. The established risk nomogram had good discriminative ability and accuracy. Involved sFLC was a key factor affecting renal recovery. Starting treatment as soon as possible after detecting RI and achieving deep hematologic remission during the first 3 courses of treatment helped achieve renal recovery and improve prognosis.

ML-based sequential analysis to assist selection between VMP and RD for newly diagnosed multiple myeloma

Optimal first-line treatment that enables deeper and longer remission is crucially important for newly diagnosed multiple myeloma (NDMM). In this study, we developed the machine learning (ML) models predicting overall survival (OS) or response of the transplant-ineligible NDMM patients when treated by one of the two regimens—bortezomib plus melphalan plus prednisone (VMP) or lenalidomide plus dexamethasone (RD). Demographic and clinical characteristics obtained during diagnosis were used to train the ML models, which enabled treatment-specific risk stratification. Survival was superior when the patients were treated with the regimen to which they were low risk. The largest difference in OS was observed in the VMP-low risk & RD-high risk group, who recorded a hazard ratio of 0.15 (95% CI: 0.04–0.55) when treated with VMP vs. RD regimen. Retrospective analysis showed that the use of the ML models might have helped to improve the survival and/or response of up to 202 (39%) patients among the entire cohort (N = 514). In this manner, we believe that the ML models trained on clinical data available at diagnosis can assist the individualized selection of optimal first-line treatment for transplant-ineligible NDMM patients.

Vitamin D deficiency linked to abnormal bone and lipid metabolism predicts high-risk multiple myeloma with poorer prognosis.

Vitamin D deficiency is frequent in patients with multiple myeloma (MM), however, its prognostic relevance in MM was rather inconclusive. We first investigated the association of vitamin D deficiency with abnormal bone and lipid metabolism in newly diagnosed multiple myeloma (NDMM), and next assessed the impact of serum ratio of vitamin D to carboxy-terminal telopeptide of type I collagen (β-CTX) on progression-free survival (PFS) and overall free survival (OS) in patients with NDMM. The data of 431 consecutive patients with NDMM at Beijing Jishuitan Hospital from September 2013 to December 2022 were collected and retrospectively reviewed through our electronic medical record system. The measurement of 25-hydroxyvitamin D in the blood is an indicator of an individual's overall vitamin D status. The serum levels of vitamin D were negatively correlated with β-CTX in NDMM patients. Of note, positive correlation between vitamin D and cholesterol levels in the serum was found in this study. The cohort (n = 431) was divided into two groups based on the serum ratio of vitamin D to β-CTX. Compared to the group with a higher vitamin D to β-CTX ratio, the group with a lower vitamin D to β-CTX ratio (n = 257, 60%) exhibited hypocholesterolemia, inferior PFS and OS, along with increased cases of ISS stage-III and R-ISS stage-III, a higher number of plasma cells in the bone marrow, and elevated serum calcium levels. Consistent with this, multivariate analysis confirmed that the vitamin D to β-CTX ratio was an independent unfavorable indicator for survival in NDMM patients. Our data demonstrated the ratio of vitamin D to β-CTX in the serum is a unique biomarker for NDMM patients to identify the high-risk cases with poor prognosis, which is superior to vitamin D itself for predicting PFS and OS in NDMM. Also, it is worth mentioning that our data on the connection between vitamin D deficiency and hypocholesterolemia might help clarify novel mechanistic aspects of myeloma development.

Thrombosis events in Chinese patients with newly diagnosed multiple myeloma.

A high risk of thrombosis is seen in patients with newly diagnosed multiple myeloma (NDMM), particularly those treated with immunomodulatory drugs (IMiDs). Large cohorts addressing the thrombosis issue of NDMM patients in Asia are lacking. We retrospectively analyzed the clinical information of NDMM patients diagnosed in Zhongshan Hospital Fudan University, a national medical center, from January 2013 to June 2021. Death and thrombotic events (TEs) were the endpoints. To investigate risk factors for TEs, the Fine and Gray competing risk regression models were created, in which unrelated deaths were labeled as competing risk events. A total of 931 NDMM patients were recruited in our study. The median follow-up was 23months [interquartile range (IQR): 9-43months]. Forty-two patients (4.51%) developed TEs, including 40 cases (4.30%) of venous thrombosis and 2 cases (0.21%) of arterial thrombosis. The median time from taking first-line treatment to TEs occurrence was 2.03months (IQR: 0.52-5.70months). The cumulative incidence of TEs was higher in patients treated with IMiDs than in those without IMiDs (8.25 vs. 4.32%, p = 0.038). There was no difference in the incidence of TEs between lenalidomide-based and thalidomide-based groups (7.80 vs. 8.84%, p = 0.886). Besides, TEs occurrence did not adversely affectOS (p = 0.150) or PFS (p = 0.210) in MM patients. Chinese NDMM patients have a lower incidence of thrombosis than those in western countries. The risk of thrombosis was particularly increased in patients treated with IMiDs. TEs were not associated with inferior progression-free survival or overall survival.

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

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. 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. 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. 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.

The R2-ISS in a Multicenter Cohort of Chinese Patients With Newly Diagnosed Multiple Myeloma.

The R2-ISS in a Multicenter Cohort of Chinese Patients With Newly Diagnosed Multiple Myeloma.

Clinical Characteristics and Nomogram Model of Nosocomial Infection in Patients with Newly Diagnosed Multiple Myeloma

To explore the clinical characteristics of nosocomial infection in newly diagnosed multiple myeloma(NDMM) patients, and establish a predictive nomogram model. The clinical data of 164 patients with MM who were treated in Shanxi Bethune Hospital from January 2017 to December 2021 were retrospectively analyzed. The clinical characteristics of infection were analyzed. Infections were grouped as microbiologically defined infections and clinically defined infections. Univariate and multivariate regression models were used to analyze the risk factors of infection. A nomogram was established. 164 patients with NDMM were included in this study, and 122 patients (74.4%) were infected. The incidence of clinically defined infection was the highest (89 cases, 73.0%), followed by microbial infection (33 cases, 27.0%). Among 122 cases of infection, 89 cases (73.0%) had CTCAE grade 3 or above. The most common site of infection was lower respiratory in 52 cases (39.4%), upper respiratory tract in 45 cases (34.1%), and urinary system in 13 cases (9.8%). Bacteria(73.1%) were the main pathogens of infection. Univariate analysis showed that ECOG ≥2, ISS stage Ⅲ, C-reactive protein ≥10 mg/L, serum Creatinine ≥177 μmol/L had higher correlation with nosocomial infection in patients with NDMM. Multivariate regression analysis showed that C-reactive protein ≥10 mg/L (P＜0.001), ECOG ≥2 (P=0.011) and ISS stage Ⅲ （P=0.024） were independent risk factors for infection in patients with NDMM. The nomogram model established based on this has good accuracy and discrimination. The C-index of the nomogram was 0.779（95%CI: 0.682-0.875）. Median follow-up time was 17.5 months, the median OS of the two groups was not reached (P=0.285). Patients with NDMM are prone to bacterial infection during hospitalization. C-reactive protein ≥10 mg/L, ECOG ≥2 and ISS stage Ⅲ are the risk factors of nosocomial infection in NDMM patients. The nomogram prediction model established based on this has great prediction value.