Optimal infused CD34+ cell dose in multiple myeloma patients undergoing upfront autologous hematopoietic stem cell transplantation.

Autologous transplantation remains the standard of care for eligible multiple myeloma (MM) patients, yet optimal CD34+ cell dose remains unclear. We conducted a retrospective study on MM patients undergoing upfront transplant between 2005 and 2021 and divided them into low (≤2.5 × 106 cells/kg) and high (>2.5 × 106 cells/kg) CD34+ dose groups. We included 2479 patients, 95 in the low CD34+ group and 2384 in the high CD34+ group. Patients in the low CD34+ group were older (63.2 vs 61.1 years, p = 0.013), more often had R-ISS III (19% vs 9%, p = 0.014), received plerixafor (60% vs 35%, p < 0.001) and transplanted after 2009 (88% vs 80%, p = 0.047). Time to neutrophil and platelet recovery was longer in the low CD34+ group. Median PFS and OS were lower in the low CD34+ group (31.6 vs. 43.6 months, p = 0.011 and 76.4 vs. 108.2 months, p < 0.001, respectively). Evaluation of incrementally higher CD34+ dose did not show significant improvement in survival at thresholds >2.5 × 106 cells/kg. Multivariable analysis affirmed that CD34+ >2.5 × 106 cells/kg was associated with better PFS (HR 0.71, p = 0.008) and OS (0.59, p < 0.001). After propensity score matching, a CD34+ dose >2.5 × 106 cells/kg remained a predictor of better OS (0.42, p < 0.001). In conclusion, CD34+ dose >2.5 × 106 cells/kg was associated with improved survival, without any additional benefit at incrementally higher doses.

Improving Health Outcomes Through Treatment Sequencing Optimization in Multiple Myeloma: A Simulation Model in Transplant-Ineligible Patients.

OBJECTIVES: Patients with multiple myeloma often require multiple treatment lines. The order in which treatments are sequenced has impact on clinical outcomes. This study aimed to estimate progression-free survival (PFS) and overall survival (OS) with common treatment sequences used in Portugal and the incremental benefit of an optimal sequence in transplant-ineligible patients with multiple myeloma. METHODS: A state-transition sequential model with a five-health state conceptual structure was developed to simulate and compare survival outcomes between treatment sequences up to four lines of treatments. Data sources included randomized clinical trials and indirect treatment comparisons. A panel of Portuguese hematologists listed four most common treatment sequences and optimal sequence of choice in transplant-ineligible patients. RESULTS: Our simulation estimated an OS between 6.1 and 7.8 years using the most common sequences, with VMP + DRd + Pd + Kd as the most effective (7.8 years). Optimal sequence of choice (DRd + PVd + Kd + Vd) achieved OS of 9.8 years and may extend OS in 2.0-3.7 years vs. most common sequences (26%-61% increase). This benefit was mostly explained by extended PFS in the first line of treatment. CONCLUSION: Model results demonstrate that choosing the most effective treatment upfront is crucial in delaying disease progression thus yielding better survival outcomes in transplant-ineligible patients. There was a clear survival benefit in using daratumumab-based regimens in first line. This modelling exercise highlights the need to raise awareness around the impact of sequencing strategies to improve patient's outcomes.

Analysis of Correlation between Blood Inflammation Indicators in Peripheral Blood and Prognosis of Patients with Multiple Myeloma.

BACKGROUND: This study aimed to investigate the value of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) in the prognosis of patients with multiple myeloma (MM). METHODS: Before treatment, the NLR and LMR and all clinical indicators of 168 patients, diagnosed with MM at the Affiliated Hospital of Southwest Medical University from April 2013 to April 2022, were retrospectively analyzed, and the patients were grouped according to their median NLR counts and median LMR counts. Differences between the groups were compared by using the chi-squared (χ²) test, the Kaplan-Meier survival curve and Log-rank test were used for survival analysis and difference comparison, and the COX proportional risk model was constructed to analyze the factors affecting the prognosis of the MM patients. The test level was α = 0.05. RESULTS: The groups were divided into high NLR group (> 2.19) and low NLR group (≤ 2.19) and high LMR group (> 3.45) and low LMR group (≤ 3.45), according to the median NLR and LMR values. The clinical stage, blood ß2 microglobulin, and serum creatinine levels in the high NLR group were higher than in the low NLR group, and the differences between the groups were statistically significant (p < 0.05). The clinical stage and blood ß2 microglobulin in the low LMR group were higher than in the high LMR group, and the differences between the groups were statistically significant (p < 0.05). The Cox univariate and multivariate analyses showed that peripheral blood NLR < 2.19 and LMR ≤ 3.45 were independent risk factors for the prognosis in patients with MM (p < 0.05). CONCLUSIONS: High NLR and low LMR counts of peripheral blood suggest a poor prognosis; NLR and LMR may be prognostic indicators in MM patients.

Clinical Outcome of Induction Treatment in the Era of Novel Agents and the Impact of the Number of High-Risk Cytogenetic Abnormalities (HRA) on Prognosis of Patients With Newly Diagnosed Multiple Myeloma (NDMM): Insights From a Multicenter Study.

BACKGROUND: In the era of novel agents, the clinical outcomes of induction treatment and the impact of the number of high-risk cytogenetic abnormalities (HRA) in newly diagnosed multiple myeloma (NDMM) need to be explored. OBJECTIVE: Through this study, we aim to analyze the effectiveness of different induction treatments and explore the survival outcomes of patients with varying numbers of HRA. METHODS: A total of 734 patients from seven medical centers were included in our study. RESULTS: Patients in the CD38 monoclonal antibody or IMiDs plus proteasome inhibitors (PI) groups had significantly superior overall survival (OS) and progression-free survival (PFS) compared to those receiving IMiDs or PI alone. Additionally, the CD38 monoclonal antibody conferred a PFS advantage over IMiDs plus PI. Patients with ≥ 2 high-risk cytogenetic abnormalities (HRA) exhibited an extremely poor prognosis and should be considered ultra-high-risk individuals in multiple myeloma (MM). The CD38 monoclonal antibody, transplantation, and achieving minimal residual disease (MRD) negativity only partly mitigated the poor prognosis in patients with HRA. Furthermore, patients with 1q21 gain/amplification (1q21+) only had a significantly worse prognosis compared to patients without HRA, and those with 1q21+ plus del17p or t(4;14) exhibited an inferior prognosis compared to those with 1q21+ alone. CONCLUSION: Our results suggested that double-hit multiple myeloma was associated with extremely poor survival outcomes, and more effective treatments needed to be explored for this particular subtype of MM.

Progression of disease within 24 months (POD24) in multiple myeloma implicates poor prognosis and limitations of current prediction models for POD24.

Multiple myeloma (MM) is a common hematological malignancy, and its prognostic factors have been extensively studied. Progression of disease within 24 months (POD24) suggests a poor prognosis in many malignancies, but is rarely mentioned in MM. This study aimed to investigate the prognostic value of POD24 in MM and risk factors of POD24, and to evaluate the predictive value of existing MM prognostic models for POD24. The research retrospectively analyzed the clinical data of MM patients and found that the occurrence of POD24 is an independent prognostic factor affecting overall survival in MM, while non-transplantion and genetic abnormality are independent risk factors for the occurrence of POD24. The existing prognostic models are not effective in predicting POD24. Therefore, it's still necessary to explore a prognostic model that can predict POD24 more accurately.

Comparative analysis of single versus tandem autologous stem cell transplantation in patients with multiple myeloma in Korea: the KMM2102 study.

Tandem autologous stem cell transplantation can improve the prognosis of patients with multiple myeloma. However, the precise role of tandem transplantation remains debatable. We evaluated the clinical benefits of tandem transplantation retrospectively. Of the 655 included patients, 117 underwent tandem transplantation; the remaining were assigned to the control group. After a single transplantation, the tandem group achieved a complete remission (CR) rate of 24.8%, which increased to 46.2% after a second transplantation. The tandem group had a significantly longer median PFS than the control group in patients with International Staging System (ISS) III and high-risk cytogenetics (23.1 vs. 14.7 months, p = 0.007 for ISS III; 21.7 vs. 13.2 months, p = 0.042 for high-risk cytogenetics). The tandem group exhibited significantly superior PFS to the control group (20.3 vs. 12.6 months, p = 0.003) among patients who failed to achieve CR after a single transplantation. Tandem transplantation was associated with significantly improved PFS after adjusting for maintenance therapy in patients with ISS III, those with high-risk cytogenetics, and those who did not achieve CR after a single transplantation. Following propensity score matching, the tandem group exhibited significantly longer PFS than the control group (30.3 vs. 13.5 months, p = 0.028). Tandem transplantation should be considered in high-risk patients.

Challenges in the treatment of soft-tissue plasmacytoma: a retrospective analysis of 120 patients with extramedullary multiple myeloma.

PURPOSE: Despite the development of novel drugs and the widespread use of hematopoietic cell transplantation, the prognosis of patients (pts) with multiple myeloma and extramedullary involvement (soft-tissue plasmacytoma, STP) is rather unfavorable. METHODS: A retrospective analysis of 120 pts with STP treated between 2007 and 2022 was performed. The effects of demographic and clinical characteristics on treatment response, progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS: The rate of serological response to first-line STP treatment (at least partial remission) was 67%, and the rate of imaging response was 59%. With a median follow-up of 84.2 months, the median PFS was 10.5 months (primary STP: 20.2 months; secondary STP: 5.8 months), and the median OS was 24.5 months (primary STP: 34.5 months; secondary STP: 12.4 months). Based on the multivariate regression analysis, secondary STP (HRPFS 2.75; HROS 2.63) and organ involvement (HRPFS 1.45; HROS 1.68) were found to be negative prognostic factors of both PFS and OS. In a prognostic model, pts with at least one of these factors had a significantly worse PFS (HRPFS 3.31) and OS (HROS 3.45) than those with none risk factor. CONCLUSION: In pts with STP, risk-adapted treatment strategies including immunotherapies and cell therapies are urgently required.

Angiogenesis and multiple myeloma: Exploring prognostic potential of adrenomedullin.

BACKGROUND: Adrenomedullin (AM) is a multifunctional peptide which under basal conditions mainly regulates vasodilation and maintains vascular integrity but is also implicated in the pathogenesis of several malignancies, including multiple myeloma (MM). It has been shown that adrenomedullin is expressed by human myeloma cell lines and that it enhances MM-driven angiogenesis. However, the clinical impact of AM remains unknown. MATERIALS AND METHODS: On that basis, we enrolled 32 newly diagnosed multiple myeloma patients (NDMM) and studied the potential of AM as a prognostic biomarker. RESULTS: We report that elevated levels of AM trend with suboptimal treatment response and inferior survival of NDMM patients.

Chromosome 1q21 Aberrations Are Poor Prognostic Factors for Newly Diagnosed Multiple Myeloma Patients.

BACKGROUND: Chromosome 1q21 aberrations are one of the most common cytogenetic abnormalities in patients with multiple myeloma (MM). However, the prognostic value remains controversial. This study aimed to determine the prognostic value of numerical abnormalities of chromosome 1q21 for newly diagnosed patients with MM patients in Chinese population. METHODS: We retrospectively analyzed 629 patients with newly diagnosed MM who received the detection of chromosome 1q21 by fluorescence in situ hybridization in China. RESULTS: Among 629 patients, 309 (49.1%) had 1q21 abnormalities, of which 187 (29.7%) had three copies and 122 (19.4%) had four or more copies. Patients with two copies of 1q21 had a significantly longer median overall survival (OS) than those with three copies or ≥4 copies and also had longer progression-free survival (PFS). However, patients with three or ≥4 copies had similar OS and PFS. Univariate Cox proportional hazards regression analyses determined that 1q21 aberrations are associated with shorter OS and PFS. 1q21 aberrations are also independent poor prognostic factors for OS and PFS in multivariable analyses. Del(17p), t(4;14), and t(14;16) are common high-risk cytogenetic abnormalities (HRCAs) in patients with MM. Patients with 1q21+ alone or 1q21+ combined with HRCAs had shorter OS and PFS than patients without cytogenetic abnormalities. Patients with 1q21+ and t(11;14) also had shorter PFS but had similar OS than patients without cytogenetic abnormalities. CONCLUSION: Our study showed that chromosome 1q21 aberrations are poor prognostic factors for newly diagnosed patients with MM.

Leukaemia, lymphoma, and multiple myeloma mortality after low-level exposure to ionising radiation in nuclear workers (INWORKS): updated findings from an international cohort study.

BACKGROUND: A major update to the International Nuclear Workers Study (INWORKS) was undertaken to strengthen understanding of associations between low-dose exposure to penetrating forms of ionising radiation and mortality. Here, we report on associations between radiation dose and mortality due to haematological malignancies. METHODS: We assembled a cohort of 309 932 radiation-monitored workers (269 487 [87%] males and 40 445 [13%] females) employed for at least 1 year by a nuclear facility in France (60 697 workers), the UK (147 872 workers), and the USA (101 363 workers). Workers were individually monitored for external radiation exposure and followed-up from Jan 1, 1944, to Dec 31, 2016, accruing 10·72 million person-years of follow-up. Radiation-mortality associations were quantified in terms of the excess relative rate (ERR) per Gy of radiation dose to red bone marrow for leukaemia excluding chronic lymphocytic leukaemia (CLL), as well as subtypes of leukaemia, myelodysplastic syndromes, non-Hodgkin and Hodgkin lymphomas, and multiple myeloma. Estimates of association were obtained using Poisson regression methods. FINDINGS: The association between cumulative dose to red bone marrow, lagged 2 years, and leukaemia (excluding CLL) mortality was well described by a linear model (ERR per Gy 2·68, 90% CI 1·13 to 4·55, n=771) and was not modified by neutron exposure, internal contamination monitoring status, or period of hire. Positive associations were also observed for chronic myeloid leukaemia (9·57, 4·00 to 17·91, n=122) and myelodysplastic syndromes alone (3·19, 0·35 to 7·33, n=163) or combined with acute myeloid leukaemia (1·55, 0·05 to 3·42, n=598). No significant association was observed for acute lymphoblastic leukaemia (4·25, -4·19 to 19·32, n=49) or CLL (0·20, -1·81 to 2·21, n=242). A positive association was observed between radiation dose and multiple myeloma (1·62, 0·06 to 3·64, n=527) whereas minimal evidence of association was observed between radiation dose and non-Hodgkin lymphoma (0·27, -0·61 to 1·39, n=1146) or Hodgkin lymphoma (0·60, -3·64 to 4·83, n=122) mortality. INTERPRETATION: This study reports a positive association between protracted low dose exposure to ionising radiation and mortality due to some haematological malignancies. Given the relatively low doses typically accrued by workers in this study (16 mGy average cumulative red bone marrow dose) the radiation attributable absolute risk of leukaemia mortality in this population is low (one excess death in 10 000 workers over a 35-year period). These results can inform radiation protection standards and will provide input for discussions on the radiation protection system. FUNDING: National Cancer Institute, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Institut de Radioprotection et de Sûreté Nucléaire, Orano, Electricité de France, UK Health Security Agency. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Enhanced platelet function through CAR-T cell therapy in relapsed/refractory multiple myeloma.

The influence of chimeric antigen receptor T (CAR-T) cell therapy on platelet function in relapsed/refractory (R/R) multiple myeloma (MM) has not been thoroughly investigated. Our cohort comprised fifty MM patients treated with CAR-T cells. The mean platelet closure time (PCT) induced by collagen/adenosine diphosphate (CADP) in peripheral blood was significantly prolonged before lymphodepletion (195.24 ± 11.740 s) and notably reduced post-CAR-T cell therapy (128.02 ± 5.60 s), with a statistically significant improvement (67.22, 95% CI 46.91-87.53, P < 0.001). This post-treatment PCT was not significantly different from that of healthy controls (10.64, 95% CI 1.11-22.40, P > 0.05). Furthermore, a pronounced enhancement in PCT was observed in patients with a response greater than partial remission (PR) following CAR-T cell infusion compared to pre-treatment values (P < 0.001). An extended PCT was also associated with a less favorable remission status. In patients with cytokine release syndrome (CRS) grades 0-2, those with a PCT over 240.5 s exhibited a shorter progression-free survival (PFS), with median PFS times of 10.2 months for the PCT > 240.5 s group versus 22.0 months for the PCT ≤ 240.5 s group. Multivariate analysis revealed that a PCT value exceeding 240.5 s is an independent prognostic factor for overall survival (OS) in R/R MM patients after CAR-T cell therapy. The study demonstrates that CAR-T cell therapy enhances platelet function in R/R MM patients, and PCT emerges as a potential prognostic biomarker for the efficacy of CAR-T cell therapy.

A predictive risk-scoring model for survival prognosis of multiple myeloma based on gain/amplification of 1q21: Experience in a tertiary hospital in South-Western China.

BACKGROUND: Chromosomal 1q gains and amplifications (+1q21) are frequently observed in patients with newly diagnosed multiple myeloma (NDMM). However, the interpretation of the high-risk (HR) prognostic implications stemming from 1q21 abnormalities remain challenging to implement effectively. METHODS: In a comprehensive analysis of 367 consecutive patients with symptomatic MM, we assessed the prognostic significance of +1q21 using FISH with a threshold of 7.4%. The patient cohort was randomly divided into a training set (66.5%, n = 244) and a validation set (33.5%, n = 133). A multivariate Cox regression analysis was conducted to identify significant prognostic factors associated with PFS. Weight scores were assigned to each risk factor based on the ß-value of the corresponding regression coefficient. A predictive risk-scoring model involving +1q21 was then developed, utilizing the total score derived from these weight scores. The model's discriminative ability was evaluated using the AUC in both the training and validation sets. Finally, we compared the performance of the +1q21-involved risk with the established R-ISS and R2-ISS models. RESULTS: Upon initial diagnosis, 159 patients (43.32%) exhibited +1q21, with 94 (59.11%) having three copies, referred to as Gain(1q21), and 65 (40.89%) possessing four or more copies, referred to as Amp (1q21). Both were significantly linked to a reduced PFS in myeloma (p < 0.05), which could be effectively mitigated by ASCT. The +1q21-involved risk model, with an AUC of 0.697 in the training set and 0.725 in the validation set, was constructed including Gain(1q21), Amp(1q21), no-ASCT, and TP53 deletion. This model, termed the ultra-high-risk (UHR) model, demonstrated superior performance in predicting shorter PFS compared to the R-ISS stage 3 and R2-ISS stage 4. CONCLUSION: The UHR model, which integrates the presence of +1q21 with no-ASCT and TP53 deletion, is designed to identify the early relapse subgroup among patients with +1q21 in NDMM.

The correlation between serum bone metabolism indexes and bone disease and survival in newly diagnosed multiple myeloma patients.

Objective Myeloma-related bone disease (MBD) is one of the most common complications of multiple myeloma (MM). This study aims to investigate the correlation between serum bone metabolism indexes (BMIs), the clinical characteristics and prognosis of newly diagnosed MM (NDMM) patients. METHODS: The serum BMIs of 148 patients with NDMM in a single hematological disease treatment center from April 2014 to December 2019 were analyzed retrospectively, including type I collagen amino terminal elongation peptide (PINP), ß-C-terminal telopeptide of type I collagen (ß-CTX) and N-terminal osteocalcin (N-MID). Other clinical indexes were simultaneously collected and the degree of bone damage in patients was evaluated. We explored the effect of serum BMIs on the prognosis and identified independent prognostic factors. Another 77 NDMM patients from April 2018 to February 2021 served as the validation cohort. RESULTS: The area under the curve (AUC) predicted by ß-C-terminal telopeptide of type I collagen (ß-CTX), type I collagen amino terminal elongation peptide (PINP), and N-terminal osteocalcin (N-MID) for overall survival (OS) were 0.708, 0.613, and 0.538, respectively. Patients with high serum levels had shorter OS (p < .001, p = .004, p = .027, respectively). Cox multivariate analysis indicated that serum ß- CTX、lactic dehydrogenase、hemoglobin and the degree of bone injury were independent prognostic factors. A COX regression model was established with a C-index of 0.782 and validated with a C-index of 0.711. CONCLUSION: The serum BMIs are correlated with the patients' OS, and ß- CTX can be an independent prognostic factor.

Bortezomib, lenalidomide, and dexamethasone versus bortezomib, doxorubicin, and dexamethasone in newly diagnosed multiple myeloma.

Bortezomib, lenalidomide, and dexamethasone (VRD), and bortezomib, doxorubicin, and dexamethasone (PAD), are commonly used in induction regimens for patients with newly diagnosed multiple myeloma (NDMM) in China. This real-world study enrolled 390 patients, 195 receiving VRD and 195 receiving PAD induction. The primary endpoint was progression-free survival (PFS) and stringent complete remission/complete remission. Across the entire cohort, VRD demonstrated significantly improved five-year overall survival (OS) (74% vs. 59%, p = 0.0024) and five-year PFS (67% vs. 37%, p = 0.0018) compared to PAD. Notably, the median OS and PFS were not reached for VRD-treated patients, while they were 77 months (60-not reached [NR]) and 46 months (36-NR), respectively, for PAD. In patients with standard-risk cytogenetics, VRD showed superior five-year OS (83% vs. 58%, p = 0.0038) and PFS (78% vs. 48%, p = 0.0091) compared to PAD. However, these differences were not statistically significant in high-risk patients. For transplanted patients, VRD was associated with superior five-year OS (91% vs. 67%, p = 0.014) and PFS (79% vs. 47%, p = 0.015) compared to PAD. In non-transplanted patients, VRD showed a trend towards improved five-year OS (p = 0.085) and PFS (p = 0.073) compared to the PAD group. In conclusion, VRD displayed superior OS and PFS outcomes in standard-risk patients and those who underwent transplantation. These findings suggest potential advantages of VRD over PAD in real-world clinical settings for NDMM treatment. However, due to the imbalance in transplantation rates between the VRD and PAD groups, limitations in testing for high-risk cytogenetic abnormalities (HRA), and the difference between the received cycles and salvage therapies, the conclusions of this study should be interpreted with caution.

Risk assessment and clinical implications of COVID-19 in multiple myeloma patients: A systematic review and meta-analysis.

INTRODUCTION: Patients with multiple myeloma (MM) face heightened infection susceptibility, particularly severe risks from COVID-19. This study, the first systematic review in its domain, seeks to assess the impacts of COVID-19 on MM patients. METHOD: Adhering to PRISMA guidelines and PROSPERO registration (ID: CRD42023407784), this study conducted an exhaustive literature search from January 1, 2020, to April 12, 2024, using specified search terms in major databases (PubMed, EMBASE, and Web of Science). Quality assessment utilized the JBI Critical checklist, while publication bias was assessed using Egger's test and funnel plot. The leave-one-out sensitivity analyses were performed to assess the robustness of the results by excluding one study at a time to identify studies with a high risk of bias or those that significantly influenced the overall effect size. Data synthesis involved fitting a random-effects model and estimating meta-regression coefficients. RESULTS: A total of 14 studies, encompassing a sample size of 3214 yielded pooled estimates indicating a hospitalization rate of 53% (95% CI: 40.81, 65.93) with considerable heterogeneity across studies (I2 = 99%). The ICU admission rate was 17% (95% CI: 11.74, 21.37), also with significant heterogeneity (I2 = 94%). The pooled mortality rate was 22% (95% CI: 15.33, 28.93), showing high heterogeneity (I2 = 97%). The pooled survival rate stood at 78% (95% CI: 71.07, 84.67), again exhibiting substantial heterogeneity (I2 = 97%). Subgroup analysis and meta-regression highlighted that study types, demographic factors, and patient comorbidities significantly contributed to the observed outcome heterogeneity, revealing distinct patterns. Mortality rates increased by 15% for participants with a median age above 67 years. ICU admission rates were positively correlated with obesity, with a 20% increase for groups with at least 19% obesity. Mortality rates rose by 33% for the group of patients with at least 19% obesity, while survival rates decreased by 33% in the same group. CONCLUSION: Our meta-analysis sheds light on diverse COVID-19 outcomes in multiple myeloma. Heterogeneity underscores complexities, and study types, demographics, and co-morbidities significantly influence results, emphasizing the nuanced interplay of factors.

Efficacy of daratumumab on multiple myeloma patients with renal insufficiency: a systematic review and meta-analysis.

BACKGROUND: Renal insufficiency (RI) is a key factor affecting the prognosis of multiple myeloma (MM) patients. Because the benefit of daratumumab for treating MM patients with RI remains unclear, our objective was to evaluate the efficacy of daratumumab on MM patients with RI. METHODS: We conducted a systematic search of the PubMed, EMBASE, and Cochrane Library databases as of October 24, 2023. Two independent reviewers screened the article titles, abstracts, and full text to identify the randomized controlled trials (RCTs) meeting the inclusion and exclusion criteria. Meta-analyses were performed using RevMan version 5.4. Outcomes of interest were progression-free survival (PFS), overall survival (OS), complete response or better (≥CR), and minimal residual disease (MRD) negativity, all calculated as hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: A total of 10 RCTs with 5003 patients were included. Add-on daratumumab improved PFS and OS among newly diagnosed MM (NDMM) patients with RI (HR 0.48 [95% CI: 0.36, 0.64, I2 = 65%] and HR 0.63 [95% CI: 0.48, 0.82, I2 = 0%]) as well as relapsed/refractory MM (RRMM)-RI patients, compared with the control group (HR 0.46 [95% CI: 0.37, 0.58, I2 = 0%] and HR 0.68 [95% CI: 0.51, 0.92, I2 = 0%]). In terms of the renal status, the efficacy of add-on daratumumab for MMRI patients was similar to that for MM patients with normal renal function. A prolonged PFS benefit for add-on daratumumab treatment versus the control was evident across all RRMM-RI subgroups, and the benefits tended to increase with the follow-up time. CONCLUSIONS: Our results indicate that MM patients with RI could benefit from a daratumumab-added regimen regardless of MM status. Additional high-quality RCTs are still warranted to confirm our findings.

Modest survival benefits of autologous stem cell transplantation in multiple myeloma with renal impairment: a critical appraisal of the pre-antibody era.

The benefit of high-dose melphalan followed by autologous hematopoietic stem cell transplantation (HDM-ASCT) for multiple myeloma (MM) patients with renal insufficiency (RI) is debated. A systematic review and meta-analysis were conducted to assess the safety and efficacy of HDM-ASCT in MM patients with RIs, and the findings were compared with real-world data. The study included 26 articles, 13 of which were pooled for meta-analysis. We compared three different types of MM patients with RI against MM patients with normal renal function (NRF). These patients were: MM patients with RI at the time of transplantation; MM patients with RI at the time of diagnosis; MM patients with RI at diagnosis but with NRF at transplantation. The meta-analysis indicated that MM patients with RIs conditioned with melphalan ≤ 140 mg/m2 followed by ASCT had transplant-related mortality rates comparable to those without RIs. The complete response rates post-ASCT were similar between MM patients with RIs and those with NRF. Although progression-free survival (PFS) was statistically similar between the groups, MM patients with RIs had significantly poorer overall survival (OS) than those with NRF. The real-world data supported these findings. With a reduced dose of melphalan, ASCT is safe and effective for MM patients with RI. MM patients with RI have similar complete response rates and PFS after ASCT compared to MM patients with NRF. The lower OS in MM patients with RI indicates the need for further research to improve OS in these patients.