Ранняя смертность у нескольких больных миеломой, страдающих почечными расстройствами: исследование по вопросам контроля за конкретными случаями.

Introduction

Multiple myeloma (MM) ranks as the second most prevalent blood cancer, representing approximately 10% of hematologic malignancies [ 1 ]. While still considered incurable, the prognosis of MM patients greatly improved in recent years due to advancements in treatment like proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies, and novel approaches like chimeric antigen receptor T cell therapy. These advances have substantially extended patient survival [ 2 , 3 ]. Nowadays, in real-world settings, the median overall survival (OS) for MM is reported to exceed 60 months [ 4 ]. Furthermore, with the introduction of anti-CD38 monoclonal antibody-based quadruplet regimens as frontline therapy, median OS has been projected to extend beyond 11 years [ 5 ].

Despite the notable advancements in the prognosis of MM, a certain proportion of MM patients still experience early death after diagnosis. Previous studies showed that prior to the availability of novel agents like PIs and IMiDs, 10% of newly diagnosed MM (NDMM) patients died within 2 months following their diagnosis, with infections being the main cause of early death [ 6 ]. Even in the era of novel agent treatments, the mortality rate within the first 12 months after diagnosis was as high as 13% [ 7 ]. Therefore, early mortality remains a clinical concern. Previous studies have identified three key categories of risk factors for early mortality in MM patients: disease-associated factors (e.g., elevated lactate dehydrogenase (LDH) [ 8 – 13 ], advanced international staging system (ISS) stage, increased beta 2-microglobin (β2-MG), renal impairment), patient-related factors (e.g., age, Eastern Cooperative Oncology Group (ECOG) performance status) [ 10 – 12 , 14 , 15 ], and treatment-related factors (e.g., use of novel agents) [ 11 ]. However, limited attention has been given to the specific cohort presenting with RI in the novel agent era.

Renal impairment (RI), also referred to as renal insufficiency or renal failure, is a common complication in MM, affecting approximately 20–40% of NDMM patients [ 16 ]. Substantial evidence indicates that MM patients with RI experience reduced survival, limited treatment options, and an increased risk of complications [ 16 – 19 ]. Consequently, proactive management of RI is essential for improving the prognosis in these patients. Additionally, some studies have reported an elevated risk of early death in MM patients with RI [ 11 , 12 , 20 , 21 ]. However, the contributing factors of early mortality specifically in NDMM patients with RI remain poorly understood. Furthermore, given the ethnic differences in renal function and obesity-related kidney disease between Chinese and Western populations, findings from Western-dominated studies may not be directly applicable to Chinese patients, highlighting the need for region-specific insights [ 22 , 23 ].

Characterized by its hybrid design that combines the advantages of cohort and case-control studies, the nested case-control study achieves minimal selection bias, making it a highly effective method for exploring disease risk factors. For these reasons, we adopted a nested case-control study design to investigate risk factors and identify clinical predictors for early mortality in MM patients with RI in novel agent era. Given that anti-CD38 monoclonal antibodies for newly diagnosed MM were only approved in China starting from May 2023, were not included in the national reimbursement list until January 2024, and coverage was initially limited to transplant-ineligible patients, this study specifically targeted MM patients with RI from the era preceding monoclonal antibody therapy. A comprehensive analysis of patient demographics, laboratory parameters and comorbidity at diagnosis was conducted to evaluate their association with early mortality.

Methods

Study population and study design

A retrospective nested case-control study was conducted to investigate risk factors associated with early mortality in NDMM patients with RI at West China Hospital of Sichuan University. As a retrospective study, the Ethics Committee approved a waiver of informed consent. The study included NDMM patients with RI over 18 years of age, diagnosed between June 2016 and November 2022, who had not received monoclonal antibody treatment. Risk factors were identified through a comprehensive literature review, available data, and expert knowledge. Baseline characteristics collected from the study cohort included gender, age, ECOG performance status, Mayo-frail score, hemoglobin levels, platelet counts, renal function, serum calcium, albumin, LDH, β2-MG, N-terminal pro-brain natriuretic peptide (NT-proBNP), type of monoclonal immunoglobulin, ISS stage, R-ISS stage, chromosomal abnormalities, fluorescence in situ hybridization (FISH) results, dialysis dependency, and comorbidities at diagnosis. Patients were followed up to gather clinical data on mortality, disease progression, and other relevant outcomes through review of medical records and routine telephone follow-up calls conducted by clinical staff. This was a retrospective analysis based on anonymized clinical data.

This study focused on identifying early mortality risk factors using baseline demographic, laboratory, and comorbidity data available at diagnosis to enable rapid risk stratification before treatment initiation. Therefore, post-treatment factors such as treatment regimens, hematologic response, and renal response were not included in the analysis. A flowchart summarizing the study cohort and patient selection process is provided in Supplementary Fig. 1 .

Definitions

All diagnoses of MM were made in accordance with the guidelines established by the International Myeloma Working Group [ 24 ]. In this study, RI referred to Durie–Salmon (DS) substage B, that was, serum creatinine ≥ 177 μmol/L or estimated glomerular filtration rate (eGFR) ≤ 40 ml/min at the time of initial diagnosis. Early mortality has been defined inconsistently in the literature, with timeframes ranging from 60 days to 6 and 12 months. In this study, we defined early mortality as death from any cause occurring within 12 months of diagnosis to ensure comparability with recent publications. OS was determined by the time span from diagnosis to either death or the most recent follow-up.

Case and control selection

All eligible NDMM patients with RI constituted the study cohort. Those who experienced early mortality within one year after diagnosis in the study cohort were considered as the case group. For each case, four controls were selected from study cohort, matched on age (+/- 5 years), sex, and date of diagnosis (+/- 1 year). All patients in the control group were followed for more than one year to ensure that none of them died within one year after diagnosis. The selected cases and matched controls collectively constituted the case-control cohort.

Statistical analysis

Frequencies and percentages were used to describe categorical variables based on the available data, whereas quantitative variables were characterized by their median and range. To assess differences in nominal variables, Fisher’s exact test was conducted. The Mann-Whitney U test was used to compare continuous variables across groups. Conditional logistic regression was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the relationship between clinical variables and the risk of early mortality in NDMM patients with renal impairment. Variables with a p value < 0.1 in univariable conditional logistic regression were further included in the multivariable logistic regression analysis. Risk factors for early mortality were identified using multivariate logistic regression analysis. Following this, we evaluated differences in OS between MM patients with and without these risk factors across the case-control cohort and the study cohort. Additionally, the impact of the number of risk factors on OS was further analyzed. The OS estimates were obtained using the Kaplan-Meier method, and the comparisons were conducted using the log-rank test. A p -value of less than 0.05 was considered statistically significant, with all p -values being two-sided. The statistical analysis was carried out using SPSS Statistics Version 26 (IBM Corp., Armonk, NY).

Results

Patients’ characteristics

The study cohort comprised a total of 199 NDMM patients with RI, including 105 males (52.8%) and 94 females (47.2%). The median age at diagnosis was 65 years, with a range of 38 to 89 years. The median serum creatinine at initial diagnosis was 267 (range 128–2015) umol/L, and the median eGFR was 18.8 (range 2–40) ml/min. The median follow-up period was 22.5 months, ranging from 0.5 to 80 months. Among the 199 MM patients with RI, 19 patients experienced early mortality, resulting in an early death incidence rate of 9.5%. Among them, 14 deaths occurred within six months of diagnosis, with 7 of these occurring within two months of diagnosis. According to the matching criteria, a control group was matched at a ratio of 1:4, resulting in 76 cases in the control group from study cohort. Table 1 illustrates the baseline characteristics of the cases and controls. Both the case group and the control group had a median age of 63 years. The case group exhibited a higher prevalence of elevated LDH levels and pneumonia compared to the control group. The median LDH levels were 308 (range 95.4–1564) IU/L for the case group and 190 (range 77–411) IU/L for the control group. The incidence of pneumonia was 9/17 (52.9%) in the case group and 16/74 (21.6%) in the control group. No appreciable differences in ECOG performance status, Mayo-frail score, hemoglobin level, platelet count, creatinine, eGFR, blood calcium, serum albumin, β2-MG, NT-proBNP, light chain type, ISS stage, R-ISS stage, chromosomal changes, 1q21 or del(17p) status, dialysis dependency, or presence of heart failure, hypertension and diabetes were observed between groups (Table 1 ).

Table 1 Baseline characteristics of cases and controls [median (range) – number (%)] Variable Overall ( N = 95) Cases ( N = 19) Matched controls ( N = 76) p -value Age, years 63 (42–84) 63 (42–84) 63 (46–84) 0.566 Hemoglobin, g/L 82 (56–158) 79 (62–117) 84.5 (56–158) 0.546 Platelet, *10 9 135 (35–681) 122 (35–681) 135 (46–345) 0.165 Creatinine, umol/L 268.5 (132–1174) 362 (136–930) 240 (132–1174) 0.571 eGFR, ml/min 18.41 (2.57-40) 14.9 (4.8-37.01) 18.69 (2.57-40) 0.449 Calcium, mmol/L, n = 84 2.37 (1.68–4.71) 2.55 (2.04–3.88) 2.36 (1.68–4.71) 0.365 Albumin, g/dL 37.5 (18.4–49.8) 34.7 (22.6–49) 37.7 (18.4–49.8) 0.351 β2-MG, mg/dL 12.2 (3.15–105) 11.7 (3.15–105) 12.6 (3.29–60.1) 0.285 Elevated LDH 34 (35.8) 13 (68.4) 21 (27.6) 0.002 NT-proBNP, ng/L, n = 63 2955 (41-35000) 4708 (127-35000) 2327 (41-24341) 0.143 Light chain, n = 93 0.304 Kappa 39 (41.9) 9 (50) 30 (40) Lambda 54 (58.1) 9 (50) 45 (60) ISS stage, n = 86 0.151 1–2 12 (14.0) 1 (5.9) 11 (15.9) 3 74 (86.0) 16 (94.1) 58 (84.1) R-ISS stage, n = 72 0.130 2 29 (40.3) 4 (25) 25 (44.6) 3 43 (59.7) 12 (75) 31 (55.4) Chromosome abnormality, n = 58 9/58 (15.5) 3/11 (27.3) 6/47 (12.8) 0.350 FISH, n = 65 Del 17p 8/65 (12.3) 2/12 (16.7) 6/53 (11.3) 0.458 IgH rearrangement 15/65 (23.1) 2/12 (16.7) 13/53 (24.5) 0.437 1q21 amplification 33/65 (50.8) 7/12 (58.3) 26/53 (53.8) 0.398 ECOG, n = 71 0.587 0–1 34/71 (47.9) 8 (47.1) 26 (48.1) 2–4 37/71 (52.1) 9 (52.8) 28 (51.9) Mayo-frail score, n = 48 0.965 0–1 19/48 (39.6) 6 (42.9) 13 (38.2) 2–3 29/48 (60.4) 8 (57.1) 21 (61.8) Dialysis dependent, n = 79 18/79 (22.8) 3/16 (18.8) 15/63 (23.8) 0.476 Comorbidity at diagnosis, n = 91 Pneumonia 25/91 (27.5) 9/17 (52.9) 16/74 (21.6) 0.013 Heart failure 13/91 (14.3) 5/17 (29.4) 8/74 (10.8) 0.062 Hypertension 28/91 (30.8) 3/17 (17.6) 25/74 (33.8) 0.157 Diabetes 17/91 (18.7) 3/17 (17.6) 14/74 (18.9) 0.605 β2-MG, beta 2-microglobin; ECOG, Eastern Cooperative Oncology Group; eGFR, estimated glomerular filtration rate; FISH, fluorescence in situ hybridization; ISS, international staging system; LDH, lactate dehydrogenase; NT-proBNP, N‐amino terminal prohormone brain natriuretic peptide; R-ISS, revised international staging system

Causes of death

Causes of early death were identified in 17 (89.5%) of the patients. Among these, infection was the most prevalent cause, accounting for 58.8% (10/17) of the cases. Within this group, pneumonia—whether present at diagnosis or developing during treatment—was the leading infection-related cause of death, affecting 7 out of 10 patients (70%). The majority of patients who succumbed to pneumonia died within three months of diagnosis. Notably, only one patient died due to disease progression, suggesting that non-relapse mortality (NRM) constitutes a significant portion of early death causes. Other reported causes of death included heart disease ( N = 2), renal failure ( N = 2), multiple organ dysfunction syndrome ( N = 1), and trauma ( N = 1).

Risk factors analysis for early death

Odds ratios (ORs) were calculated to assess the relationships between clinical variables and early mortality (Table 2 ). By univariable conditional logistic regression, elevated serum LDH levels (OR 1.011, 95% CI 1.003–1.020, p = 0.007), and presence of pneumonia (OR 3.992, 95% CI 1.267–12.579, p = 0.018) and heart failure at diagnosis (OR 2.791, 95% CI 0.834–9.340, p = 0.096) were significantly associated with a greater risk of early mortality. Conversely, other factors such as the levels of serum calcium, serum creatinine, β2-MG, hemoglobin, ECOG performance status, stage of the patient’s disease, and FISH results did not exhibit a significant correlation with early death (Table 2 ). To further validate these findings, a multivariable conditional logistic regression was conducted. This analysis confirmed that elevated LDH levels (OR 1.009, 95% CI 1.001–1.018, p = 0.023) and the presence of pneumonia (OR 5.885, 95%CI 1.097–30.342, p = 0.044) were significantly associated with increased risks of early mortality, whereas heart failure was not (OR 1.025, 95%CI 0.141–7.444, p = 0.981) (Table 2 ).

Table 2 Univariable and multivariable conditional logistic regression model for early death in MM patients with RI Variables Univariable Multivariable OR (95%CI) p -value OR (95%CI) p -value Hemoglobin, n = 95 0.988 (0.959–1.019) 0.458 Platelet, n = 95 1.001 (0.997–1.006) 0.550 Creatinine, n = 95 1.000 (0.998–1.002) 0.738 eGFR, n = 95 0.991 (0.948–1.036) 0.697 Calcium, n = 84 1.731 (0.711–4.217) 0.227 Albumin, n = 95 0.953 (0.883–1.030) 0.223 β2-MG, n = 95 1.012 (0.982–1.043) 0.442 LDH, n = 95 1.011 (1.003–1.020) 0.007 1.009 (1.001–1.018) 0.023 NT-proBNP, n = 63 1.990 (0.590–6.710) 0.267 Light chain, n = 94 0.627 (0.233–1.689) 0.356 ISS stage, n = 86 1.163 (0.207–6.522) 0.864 R-ISS stage, n = 72 1.771 (0.506–6.195) 0.371 Chromosome abnormality, n = 58 1.695 (0.360–7.989) 0.504 Del 17p, n = 65 1.160 (0.203–6.637) 0.867 IgH rearrangement, n = 65 0.841 (0.161–4.409) 0.838 1q21 amplification, n = 65 1.150 (0.300-4.407) 0.839 ECOG, n = 71 1.108 (0.315–3.288) 0.976 Mayo-frail score, n = 48 0.851 (0.217–3.329) 0.816 Dialysis dependent, n = 79 0.790 (0.191–3.268) 0.745 Pneumonia, n = 91 3.992 (1.267–12.579) 0.018 5.885 (1.097–30.342) 0.044 Heart failure, n = 91 2.791 (0.834–9.340) 0.096 1.025 (0.141–7.444) 0.981 Hypertension, n = 91 0.298 (0.056–1.586) 0.156 Diabetes, n = 91 0.950 (0.232–3.887) 0.943 β2-MG, beta 2-microglobin; ECOG, Eastern Cooperative Oncology Group; eGFR, estimated glomerular filtration rate; ISS, International Staging System; LDH, lactate dehydrogenase; NT‐proBNP, N‐amino terminal prohormone brain natriuretic peptide; R-ISS, revised international staging system

Survival outcome

In the case-control cohort ( N = 95), the 1-year OS rate was 61.8% for patients with elevated LDH levels, compared to 90% for those with normal LDH levels (HR = 2.76, 95% CI 1.54–6.55, p = 0.0016) (Fig. 1 A). For patients diagnosed with pneumonia, the 1-year OS rate was 65.4%, as opposed to 87.7% for those without pneumonia (HR = 1.88, 95% CI 0.92–4.67, p = 0.08) (Fig. 1 B). Subsequently, we assessed the impact of these two risk factors—elevated LDH and pneumonia at diagnosis—on OS within the study cohort ( N = 199), and examined how the number of risk factors influenced survival. Data from 161 patients in the study cohort were analyzed. Figure 2 A displays the OS of the study cohort, with OS rates of 96.2%, 91.3%, and 87.5% at 2 months, 6 months, and 1 year, respectively. Patients with elevated LDH exhibited a 1-year OS rate of 77.1%, in contrast to 93.6% for those without elevated LDH (HR = 2.68, 95%CI 1.9–5.9, p < 0.001, Fig. 2 B). The 1-year OS rate for patients with pneumonia at diagnosis was 77.6%, compared to 92.4% for those without pneumonia (HR = 2.16, 95%CI 1.35–4.68, p = 0.0062, Fig. 2 C). When considering pneumonia and elevated LDH at diagnosis as risk factors, the 1-year OS rates for MM patients with RI were 95.3% for those with no risk factors, 85.2% for those with one risk factor, and 68.8% for those with two risk factors ( p < 0.001) (Fig. 2 D).

Fig. 1 Comparison of overall survival between patients in the case-control cohort with elevated LDH vs. normal LDH ( A ), and with pneumonia vs. without pneumonia ( B )

Fig. 2 Overall survival of the study cohort ( A ). Comparison of overall survival in the study cohort between patients with elevated LDH vs. normal LDH ( B ), and with pneumonia vs. without pneumonia ( C ). Comparison of overall survival in the study cohort based on the number of risk factors ( D )

Discussion

With the advent of novel therapeutic approaches, the long-term prognosis for patients with MM has markedly improved [ 2 , 3 ]. However, early mortality remains a significant clinical concern, as some patients succumb early in the disease course, thus missing the potential benefits of these advancements. Many studies have explored early mortality in MM patients, highlighting factors such as age, beta-2 microglobulin, ECOG performance status, albumin levels, and LDH levels as significant predictors. However, these studies did not concentrate on MM patients with RI, a condition that is prevalent in this population and closely associated with their prognosis and treatment outcomes [ 16 , 17 ]. Unlike other research on early mortality in MM, this nested case-control study specifically targets NDMM patients with RI. The study found that the one-year mortality rate among MM patients with RI was approximately 9.5%. Infections emerged as the primary contributor to early mortality, with pulmonary infections being the most prevalent. Multivariate conditional logistic regression analysis indicated that elevated LDH levels at diagnosis and concurrent pulmonary infections significantly increased the risk of early mortality, thereby reducing the overall survival of NDMM patients with RI. These findings underscore the importance of monitoring LDH levels and assessing for concurrent pulmonary infections in NDMM patients with RI.

Previous studies have suggested that RI may increase early mortality in MM patients. However, in our cohort, the early mortality rate in NDMM patients with RI was 9.5%, which is comparable to rates reported for unselected NDMM populations [ 7 , 10 ]. When compared with the 6.9% (52/754) early mortality rate observed in all MM patients at our center during the same period, the difference was not statistically significant ( p = 0.099). These findings suggest that RI may not independently elevate early mortality risk, highlighting the need for further research to clarify the complex relationship between renal function and survival outcomes in this population.

Patients with MM exhibit profound immune dysfunction arising from multiple interrelated factors: disease-related immunosuppression (including hypogammaglobulinemia, T-cell dysfunction, and impaired phagocyte function), host-related factors (advanced age, comorbidities, and frailty), and treatment-related effects (such as proteasome inhibitors and IMiDs). Consequently, MM patients have a significantly higher risk of infections compared to healthy controls. In this study, 27.5% (25 out of 91) of patients were found to have pulmonary infections at the time of MM diagnosis, with this proportion increasing to nearly 50% among those who experienced early mortality. The study revealed that concurrent pulmonary infections not only heightened the risk of early death in MM patients with RI but also constituted the leading cause of death in these cases, accounting for approximately half of the early mortality causes. These findings align with previous research [ 6 , 25 ]. Earlier investigations, conducted before the introduction of new therapeutic agents, identified infections as the primary cause of nearly 50% of early deaths (defined as death occurring within two months of diagnosis) [ 6 ]. Similarly, data from the Danish MM registry, involving patients ineligible for transplantation, indicated that infections were responsible for about half of all early mortality instances [ 25 ]. Given that infection is the primary cause of early mortality in MM patients, patients presenting with infection should be closely monitored, and treatment strategies should be promptly adjusted to mitigate the risk of early death. Regarding preventive strategies, current guidelines recommend: (1) levofloxacin prophylaxis during the first 12 weeks for high-risk NDMM patients; (2) antiviral prophylaxis (acyclovir/valacyclovir) for herpes simplex virus (HSV) and varicella zoster virus (VZV), particularly in patients receiving proteasome inhibitors; (3) universal Pneumocystis jirovecii pneumonia (PJP) prophylaxis with trimethoprim-sulfamethoxazole; (4) Intravenous immunoglobulin (IVIG) for patients with recurrent severe infections and hypogammaglobulinemia (IgG < 400 mg/dL); and (5) vaccination against influenza and pneumococcus [ 26 ]. Although our study was not designed to evaluate these strategies, these findings highlight the need for individualized infection prevention approaches in NDMM patients with RI.

We further examined disease control status in patients who died early. Among the 17 patients with identifiable causes of death, most died within six months of diagnosis and had received only limited anti-myeloma therapy. At the time of death, most had achieved only stable disease or partial response, and two patients died before any treatment could be initiated. Poor disease control may further increase the risk of infection in these already immunocompromised patients. These findings indicate that early death in this cohort occurred in the context of inadequately controlled myeloma.

LDH is a critical marker for the ISS and serves as an important prognostic indicator in MM. Consistent with prior studies on early mortality risk in MM patients [ 8 , 13 , 25 ], our research demonstrated that elevated LDH levels significantly increased the risk of early mortality among MM patients with RI. A study by Xia J et al., which focused on identifying early mortality risk factors in elderly MM patients undergoing treatment in a clinical setting, found a significant and independent association between high LDH levels and early mortality [ 13 ]. However, some studies have not established a connection between elevated LDH levels and early mortality [ 20 , 21 ].

Although advanced age is well-established as a poor prognostic factor for both early mortality and overall survival in MM [ 10 – 14 ], cases and controls in our study were matched for age, resulting in similar age distributions between the two groups. Therefore, the independent effect of age on early mortality could not be further evaluated in this matched analysis. Additionally, other potential risk factors, including creatinine levels, β2-MG, serum albumin, ISS stage, light chain disease, and ECOG performance status, were analyzed but did not show statistically significant associations with early mortality in our study (as shown in Table 2 ).

NT-proBNP is a biomarker reflecting both cardiac and renal function [ 27 , 28 ]. Its dual role makes it a potential prognostic indicator for patients with MM. In this study, we examined whether NT-proBNP elevation and the Mayo-frailty score—which incorporates NT-proBNP along with age and ECOG performance status [ 29 ] —were associated with early mortality in NDMM patients with RI. Our analysis did not reveal significant differences in either NT-proBNP levels or Mayo-frailty score between patients who experienced early death and those who did not (Table 1 ). Although more than half of our patients scored 2–3 points on the Mayo-frailty scale—likely due to elevated NT-proBNP from reduced renal clearance in our RI cohort—neither factor was identified as an independent risk factor for early mortality in our multivariable analysis.

Relapse continues to pose a significant challenge in the management of MM, particularly for patients with extended survival times. With the introduction of novel therapeutic agents, most MM patients can achieve effective disease control during the early stages of treatment. Consequently, mortality due to disease progression in the early period after diagnosis is relatively uncommon. Consistent with this observation, our study found that only one patient succumbed to disease progression within the first year following diagnosis. Nonetheless, early-stage mortality from non-relapse-related causes, such as infections, heart failure, and renal failure, warrants increased attention and proactive management.

Other factors that may influence early mortality, such as post-treatment hematologic and renal response, and whether the patient undergoes hematopoietic stem cell transplantation, were considered but not addressed in this study, as our analysis focused on baseline predictors available at diagnosis. Our findings indicate that the peak of early mortality in MM patients occurs within the first 6 months (14/19), emphasizing the importance of baseline clinical and laboratory parameters when investigating early mortality. In contrast, long-term management of MM patients should place a greater focus on assessing treatment efficacy.

This study employed a nested case-control design to examine the risk factors associated with early mortality in MM patients with RI. This methodological approach helps mitigate selection and recall biases. Furthermore, the study reflects real-world clinical conditions, enhancing its applicability to actual patient populations. This study has several limitations. It was retrospective and conducted at a single center, which may limit generalizability. The sample size was modest, with incomplete data for some variables. Additionally, the impacts of hematologic and organ response to treatment were not evaluated in this study. Moreover, pathogen data from bronchoalveolar lavage were not available for most patients, limiting our understanding of the microbiological etiology of pulmonary infections in this cohort. Given the variability in reported risk factors for early mortality across different studies, larger multicenter prospective studies are warranted to provide a more comprehensive understanding of these risk factors.

Based on our findings, we offer the following clinical recommendations for managing NDMM patients with RI. First, clinicians should maintain a high index of suspicion for pneumonia at diagnosis, as its presence independently predicts early mortality and warrants prompt anti-infective therapy. Second, elevated LDH at diagnosis should alert physicians to a higher risk of early death, enabling early risk stratification and more vigilant supportive care, and risk-adapted treatment strategies. Third, for high-risk patients, consider prophylactic antibiotics (levofloxacin) during the first 12 weeks of treatment, antiviral prophylaxis for HSV/VZV, and IVIG for those with recurrent severe infections and hypogammaglobulinemia (IgG < 400 mg/dL). When discussing prognosis with patients and families, physicians should communicate that while the overall early mortality rate is 9.5%, the presence of pneumonia at diagnosis or elevated LDH significantly increases this risk, whereas patients without these risk factors have a 1-year survival rate of 95.3%.

Conclusions

In conclusion, this study focused on NDMM patients with RI. The findings revealed an early mortality rate of 9.5%, with infection identified as the leading cause of early death. Elevated LDH levels and the presence of pneumonia at diagnosis were significantly associated with an increased risk of early mortality. These results were corroborated by data from the overall cohort of MM patients with RI, demonstrating that individuals with more risk factors had reduced survival times. However, further research is required to validate these findings.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Material 1: Supplementary Fig. 1 Flowchart of the study cohort and patient selection process. NDMM, newly diagnosed multiple myeloma; RI, renal impairment

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Acknowledgements

Not applicable.

Author contributions

Yan Li: design, literature search, data acquisition, data analysis, statistical analysis, manuscript preparation. Wenjiao Tang: literature search, data acquisition, data analysis, manuscript editing. Bing Xiang: data acquisition, manuscript editing. Ling Pan: data acquisition, manuscript editing. Yuhuan Zheng: concept, manuscript review. Li Zhang: concept, design, manuscript editing, manuscript review. Ting Niu: concept, manuscript review. All authors read and approved the final manuscript.

Funding

This work was supported by Sichuan Medical Science and Technology Innovation Research Association (Grant No. YCH-KY-YCZD2024-106) and Key Research Project of Sichuan Anti-Cancer Association Clinical Research (Grant No. XH2023 5008).

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The study was approved by the Ethical Review Committee of West China Hospital, Sichuan University, with the need for written informed consent waived. All methods used in this study follow the principles of the Declaration of Helsinki.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Abbreviations

Beta 2-microglobin

Confidence intervals

Eastern cooperative oncology group

Immunomodulatory drugs

International staging system

lactate dehydrogenase

Multiple myeloma

Newly diagnosed MM

Non-relapse mortality

N-terminal pro-brain natriuretic peptide

Odds ratios

Overall survival

Proteasome inhibitor

Renal impairment

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