Outcomes of patients with systemic light chain amyloidosis treated with DVD front-line therapy

Abstract

A substantial proportion of patients are unsuitable candidates for the Dara-CyBorD regimen (daratumumab-cyclophosphamide-bortezomib-dexamethasone), the standard frontline treatment for systemic amyloid light-chain (AL) amyloidosis as established in the ANDROMEDA clinical trial. This is primarily due to their severe organ dysfunction and limited treatment tolerance. In this work, we evaluated an alternative frontline regimen of DVD (daratumumab-bortezomib-dexamethasone) in 64 newly diagnosed patients with AL amyloidosis, including those with advanced cardiac disease. The best hematologic response achieved was a complete response (CR) in 56.3% of patients, with very good partial response (VGPR) or better observed in 68.8%, not inferior to the hematologic responses reported in the ANDROMEDA trial. At 6 months, 13 (48.1%) achieved a cardiac response and 17 (85.0%) achieved a renal response, compared favourably to the data in ANDROMEDA. Notably, the incidence of grade ≥ 3 infections was 1.6%, significantly lower than the 7.8% reported in ANDROMEDA. The estimated 1- and 2-year overall survival (OS) rates were 84.4% and 82.8%, respectively. The profound hematologic response rates (VGPR/CR) in mayo stage IIIB patients were comparable to those in mayo stage I-IIIA patients, while the median OS of stage IIIB patients was significantly shorter than that of stage I-IIIA patients. No therapy-related deaths or permanent treatment discontinuation due to toxicity were observed. Overall, our findings demonstrate that the DVD regimen is both effective and well-tolerated, even in patients with advanced cardiac involvement.

Supplementary Information

The online version contains supplementary material available at 10.1186/s40959-026-00446-6.

Introduction

Systemic amyloid light chain (AL) amyloidosis is a plasma cell dyscrasia characterized by the deposition of monoclonal immunoglobulin light chain (LC) in tissues, leading to progressive multiorgan dysfunction and failure [1]. The primary therapeutic objective is to eradicate the clonal plasma cells to improve organ function and enhance survival. In the bortezomib-era prior to 2020, unsatisfactory hematologic response and early mortality have remained substantial challenges [2].

In the last several years, the human IgG-κ monoclonal antibody daratumumab, which targets the CD38 glycoprotein of plasma cells, has been introduced for the treatment of AL amyloidosis. In terms of mechanisms, daratumumab has both direct anti-tumor [3, 4] and immunomodulatory [5] functions. Its efficacy was initially confirmed in the treatment of relapsed or refractory AL amyloidosis [6–8], and then demonstrated in the frontline treatment through the phase 3 ANDROMEDA clinical trial. In this trial, the addition of daratumumab to cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) significantly improved hematologic and organ response rates compared to CyBorD alone [9]. Thereafter, Dara-CyBorD became the first ever-approved regimen for AL amyloidosis by the FDA and EMA. However, a considerable proportion of patients are inadequate for Dara-CyBorD due to severe organ dysfunction and poor tolerance, and patients with Mayo stage IIIB disease were therefore excluded from the ANDROMEDA study. But it is important to realize that at least 30% of AL amyloidosis patients have already progressed to advanced stage at the time of diagnosis, due to the complexity and rarity of this disease [10]. Given the efficacy of daratumumab in treating AL amyloidosis, alternative and potentially less toxic daratumumab-based regimens may be needed.

Here, we retrospectively studied the efficacy and safety of frontline daratumumab plus bortezomib and dexamethasone (DVD) treatment in newly diagnosed patients with primary systemic AL amyloidosis, including Mayo stage IIIB.

Results

Patient characteristics

Baseline demographic and clinical characteristics at diagnosis are shown in Table 1. The median age was 61 years (range, 44–83) and 70.3% were male, 73.4% had λ subtype. Patients in our cohort had a high clone burden at diagnosis, as evidenced by 21.9% with ≥ 10% bone marrow plasma cells, and 65.6% with difference between involved and uninvolved free light chain (dFLC) > 180 mg/L. At diagnosis, 22 patients (34.4%) presented with multiple myeloma defining events (MDEs): anemia in 14 (21.9%), involved/uninvolved serum free light chain ratio ≥ 100 in 10 (15.6%), and bone marrow plasma cell infiltration ≥ 60% in 5 (7.8%). One patient had more than 1 MDEs. Fluorescence in situ hybridization (FISH) analysis was available in 62 (96.9%) subjects. Amongst them, 40.6% had t(11;14) and 17.2% had 1q21 gain. At the time of treatment initiation, 82.8% of patients had ≧ 2 organs involved, including 85.9% with heart involvement and 59.4% with kidney involvement. Notably, a majority of our patients had modified Mayo 2004 stage IIIA (46.9%) or IIIB (20.3%).

Table 1.

Clinical characteristics of patients (n = 64)

Characteristics	Number of patients, n (%) or median (range)
Age, years, median (range)	61 (44–83)
Male gender, n (%)	45 (70.3)
NT-proBNP, ng/L, median (range)	6736.5 (46.8−34948.0)
hs-cTnT, pg/mL, median (range)	93.1 (12.8−408.6)
24-h UP, mg, median (range)	2348.9 (22.0−17914.5)
24-h UA, mg, median (range)	1294.7 (2.0−13392.0)
eGFR, mL/min/1.73 m2, median (range)	61.2 (16.0−102.7)
ALP, U/L, median (range)	132.5 (42.0−880.0)
dFLC, mg/L, median (range)	726.7 (14.5−6133.1)
BMPCs, %, median (range)	15.4 (1.0–38.0)
LC isotype, n (%)κλ	17 (26.6) 47 (73.4)
Mayo 2004 stage, n (%)
I	6 (9.4)
II	15 (23.4)
IIIA	30 (46.9)
IIIB	13 (20.3)
Mayo 2012 stage, n (%)
I	6 (9.4)
II	11 (17.2)
III	31 (48.4)
IV	16 (25.0)
Involved organs, n (%)
Heart	55 (85.9)
Kidney	38 (59.4)
Nervous system	22 (34.4)
Gastrointestinal tract	8 (12.5)
Liver	10 (15.6)
Soft tissue	27 (42.2)
Number of organs involved, n (%)
1	11 (17.2)
2	21 (32.8)
3	23 (35.9)
≥4	9 (14.1)
Cytogenetic abnormalities, n (%)
t(11;14)	26 (40.6)
1q21 gain	11 (17.2)
del(17p)	1 (1.6)
t(6;14)	1 (1.6)

NT-proBNP N-terminal pro-B-type natriuretic peptide, hs-cTnT high-sensitivity cardiac Troponin T, 24-h UP 24-hour urine protein, 24-h UA 24-hour urine albumin, eGFR estimated glomerular filtration rate, ALP alkaline phosphatase, dFLC difference between involved and uninvolved free light chain, BMPCs bone marrow plasma cells

Hematologic responses

The median number of cycles administered for induction therapy was 5 (1–6), and 11 patients continued to receive maintenance therapy with daratumumab after completing the first six treatment cycles. Two patients changed their treatment due to not achieving partial response (PR) at 2 months. Three patients experienced hematologic progression and discontinued treatment. None of the patients in this cohort received autologous haematopoietic cell transplantation thus far. The hematologic response data are summarized in Table 2; Fig. 1A. The percentages of patients achieving very good partial response (VGPR) or better at 1, 3 and 6 months were 43.8% (95% confidence interval [CI]: 31.4–56.7, 45.3% (95% CI: 32.8–58.3), and 48.4% (95% CI: 35.8–61.3), respectively. Considering the best hematologic response at any time point, the complete response (CR) rate was 56.3%. The study population included a subset of 43 (67.2%) patients with advanced stage (stage IIIA/IIIB), the best hematologic response rates of ≧ VGPR were 70.0% for stage IIIA and 53.8% for stage IIIB, respectively. Notably, no statistically significant differences in terms of profound hematologic response were observed between the patients with stage I-IIIA and those with stage IIIB (≧ VGPR: 70.6% for stage I-IIIA versus 53.8% for stage IIIB, p = 0.324; CR: 58.8% for stage I-IIIA versus 38.5% for stage IIIB, p = 0.224). In addition, patients with concomitant MDEs were compared with the remaining subjects. The presence of MDEs did not affect overall hematologic response rates (≧ VGPR: 42.2% for with MDEs versus 57.8% for without MDEs, p = 0.577; CR: 36.1% for with MDEs versus 63.9% for without MDEs, p = 0.374). Moreover, no differences in hematologic response rates were observed between patients with or without t (11; 14) abnormality [≧ VGPR: 40.0% for with t (11; 14) versus 60.0% for without t (11; 14), p = 1.000; CR: 36.1% for with t (11; 14) versus 63.9% for without t (11; 14), p = 0.450].

Table 2.

Summary of overall confirmed hematologic responses (n = 64)

All the patients	1 month, n (%)	3 months, n (%)	6 months, n (%)	Best hematologic response, n (%)
CR	16 (25.0)	20 (31.3)	25 (39.1)	36 (56.3)
VGPR	12 (18.8)	9 (14.1)	6 (9.4)	8 (12.5)
≧VGPR	28 (43.8)	29 (45.3)	31 (48.4)	44 (68.8)
PR	17 (26.6)	11 (17.2)	3 (4.7)	10 (15.6)
SD	7 (10.9)	2 (3.1)	0	6 (9.4)
Mayo stage IIIA (N = 30)
CR	7 (23.3)	9 (30.0)	11 (36.7)	19 (63.3)
VGPR	4 (13.3)	3 (10.0)	2 (6.7)	2 (6.7)
≧VGPR	11 (36.7)	12 (40.0)	13 (43.3)	21 (70.0)
PR	11 (36.7)	7 (23.3)	1 (3.3)	6 (20.0)
SD	3 (10.0)	2 (6.7)	0	2 (6.7)
Mayo stage IIIB (N = 13)
CR	3 (23.1)	5 (38.5)	5 (38.5)	5 (38.5)
VGPR	3 (23.1)	2 (15.4)	1 (7.7)	2 (15.4)
≧VGPR	6 (46.2)	7 (53.8)	6 (46.2)	7 (53.8)
PR	0	0	0	1 (7.7)
SD	2 (15.4)	0	0	2 (15.4)

CR complete response, VGPR very good partial response, PR partial response, SD stable disease

Fig. 1.

A Hematologic response rates at different times; B Organ response rates at 3 and 6 months

Organ responses

The organ responses are presented in Table 3; Fig. 1B. The patients with baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) < 650 pg/mL, progressive deterioration of renal function, or missing follow-up data were not assessed in the statistical analyses. At 6 months from treatment initiation, there were 27 patients evaluable for cardiac response, 20 patients evaluable for renal response, and 8 patients evaluable for hepatic response. Of the evaluable patients, 13 (48.1%) achieved a cardiac response, 11 (40.7%) had no cardiac response, 3 (11.1%) had cardiac progression; 17 (85.0%) achieved a renal response, 2 (10.0%) had no renal response, 1 (5.0%) had renal progression; 5 (62.5%) achieved a hepatic response, 3 (37.5%) had no hepatic response. We found that among the patients who achieved organ responses at 6 months, 61.5% of patients achieving cardiac response, 47.1% of patients achieving renal response, and 80.0% of patients achieving hepatic response achieved hematological responses of ≧ VGPR within 1 month, respectively, while the proportion of the entire cohort was 43.8%. This indicates that rapid hematological response may affect subsequent organ response, but further research using greater patient numbers is required for validation.

Table 3.

Summary of overall confirmed organ responses

All the patients	3 months, n (%)	6 months, n (%)	12 months, n (%)
Cardiac response CR VGPR PR ORR	1 (3.1) 1 (3.1) 13 (50.0) 15 (46.9)	0 6 (22.2) 7 (25.9) 13 (48.1)	3 (21.4) 4 (28.6) 4 (28.6) 11 (78.6)
Renal response	18 (72.0)	17 (85.0)	-
Mayo stage IIIA/IIIB
Cardiac response Renal response	11 (50.0) 11 (78.6)	10 (52.6) 8 (72.7)	- -

CR complete response, VGPR very good partial response, PR partial response, ORR overall response rate

Overall survival

After a median follow-up of 16.5 months (range, 1–46), 11 (17.2%) deaths were observed; all occurred in patients with stage III disease (5 stage IIIA; 6 stage IIIB). Amongst them, five patients died of cardiac sudden, two patients died of COVID-19, two patients died of acute liver failure, one patient died of cerebral hemorrhage, and one patient died because of heart failure exacerbation from infection. For the entire cohort, the early mortality rates (within 1 month and 3 months from treatment initiation) were 6.3% and 15.6%, respectively. The median overall survival (OS) was not reached, and the estimated 1- and 2-year OS rates were 84.4% and 82.8%, respectively (Fig. 2A). Notably, cardiac stage IIIB significantly affected OS (p = 0.004; Fig. 2B). Regarding the patients with advanced stage, the estimated 2-year OS rate was 76.7% for all stage IIIA/IIIB disease. The early mortality rate within 3 month was higher in the IIIB subgroup than in the IIIA subgroup (38.5% and 16.7%, respectively), although not statistically significant. However, the 2-year OS rate was higher in the IIIA subgroup than in the IIIB subgroup (86.7% versus 53.8%, p = 0.024). Our study also confirmed the crucial importance of achieving deep hematologic responses following treatment in AL amyloidosis. Patients achieving hematologic VGPR or better had prolonged OS in comparison to those achieving PR or stable disease (p = 0.017, data not shown). We further analyzed the impact of the most frequent cytogenetic alteration on the survivals, and we found that the presence of t(11;14) (p = 0.503; Supplementary Fig. 1) did not impact OS.

Fig. 2.

A Kaplan–Meier curve for overall survival in the entire cohort; B Kaplan–Meier survival curve showing early mortality in patients with Mayo 2004 stage IV versus stage I–III

Toxicity

The most common any grade and grade 3/4 treatment-related adverse events (AEs) are summarized in Table 4. Three patients experienced grade 1–2 infusion related reactions, solely arose with the first dosage. Grade 3/4 AEs occurred in 30 (46.9%) patients. The most common AE of any grade and grade 3/4 was lymphopenia (50.0% and 26.6%, respectively). The most common site of infection was respiratory tract (n = 18). There were no therapy-related deaths or permanent treatment discontinuation due to toxicity. Notably, the incidence rates of any grade and grade 3/4 AEs in the Mayo stage IIIB cohort were similar to those in the entire cohort, confirming that the DVD regimen was well tolerated also in subjects with advanced stage disease or severe compromised heart function.

Table 4.

Most common adverse events during treatment

Event, n (%)	All the patients (n = 64)		Mayo stage IIIB (n = 13)
	Any grade	Grade 3/4	Any grade	Grade 3/4
Hematologic
Leukopenia	18 (28.1)	0	5 (38.5)	0
Neutropenia	11 (17.2)	1 (1.6)	4 (30.8)	0
Lymphopenia	32 (50.0)	17 (26.6)	7 (53.8)	5 (38.5)
Anemia	19 (29.7)	6 (9.4)	3 (23.1)	1 (7.7)
Thrombocytopenia	21 (32.8)	4 (6.2)	5 (38.5)	1 (7.7)
Infections
Upper respiratory infection	9 (14.1)	0	1 (7.7)	0
Pneumonia	9 (14.1)	1 (1.6)	0	0
Herpes zoster	3 (4.7)	0	0	0
Diarrhea	4 (6.2)	0	0	0
Peripheral edema	2 (3.1)	0	1 (7.7)	0
Peripheral sensory neuropathy	3 (4.7)	0	0	0
Intestinal obstruction	11 (17.2)	1 (1.6)	1 (7.7)	1 (7.7)

Discussion

The ANDROMEDA clinical trial led Dara-CyBorD to be the first ever-approved regimen for AL amyloidosis, but the patients with severe cardiovascular conditions, such as NT-proBNP ≧ 8500 ng/L, were excluded from this study. Of note, stage IIIB cardiac involvement was present in approximately 17% of AL amyloidosis patients at the time of diagnosis [11], and several studies have further validated the superiority of daratumumab-based regimens in stage IIIB AL amyloidosis [12–14]. Additionally, the efficacy of the 4-drug regimen in the ANDROMEDA study comes with increased toxicity, and serious adverse events occurred in 43.0% of the patients in the daratumumab group [9]. Hence, in the past two years, we chose the triplet therapy of DVD regimen for patients with newly diagnosed AL amyloidosis, regardless of baseline tumor stage.

In the present study, the best hematologic response to DVD was a CR rate in 56.3% and ≧ VGPR rate in 68.8%, not inferior to the 53.3% CR and 78.5% ≧VGPR rates observed in ANDROMEDA. In addition, with DVD, the evaluable cardiac and renal response rates at 6 months were 48.1% and 85.0%, respectively, compared not inferior to 41.5% and 53.0% in ANDROMEDA. Meanwhile, we need to point out that the evaluable numbers may reduce statistical power. Importantly, a lower percentage of grade ≥ 3 infections (1.6%) than that in ANDROMEDA (7.8%) was observed. There was a similar study published by Kennedy et al. recently, in which 21 newly diagnosed patients treated upfront with DVD regimen achieved a hematological responses of ≧ VGPR in 81% of cases and cardiac responses in 67% of subjects, and the 1-year OS rate was 76% [15]. Taken together, these results indicate that the triplet therapy of DVD regimen abandoning cyclophosphamide in untreated systemic AL amyloidosis was effective and well tolerated, not inferior to the 4-drug regimen of Dara-CyBorD. Most importantly, the DVD regimen spared toxicities associated with cyclophosphamide, which was particularly beneficial for patients with severe cardiac dysfunction. Moreover, there have been retrospective studies to compare the outcomes of upfront bortezomib and dexamethasone with or without cyclophosphamide (VD vs. VCd) in newly diagnosed AL amyloidosis, and the results suggested that the addition of cyclophosphamide did not improve the outcomes [16, 17]. However, prospective studies are needed to evaluate the role of alkylating drugs in first-line therapy to balance the toxicity and the potential clinical benefit.

The outcome of patients with AL amyloidosis is strongly associated with cardiac stage, and the average survival time of patients with advanced stage is ≦ 6 months [10], posing an enormous challenge to treatment. In the present study, there were 43 (67.2%) patients with severe heart involvement, IIIA/IIIB cardiac stage. The results showed that the best hematologic ≧ VGPR rates were 70.0% in stage IIIA AL and 53.8% in stage IIIB AL, and the 2-year OS rates were 86.7% and 53.8% in the IIIA and IIIB subgroups, respectively. Next, we investigated hematologic response rates and survival in our cohort in comparison with previous studies. Early data from a phase 2 study on DVD in Mayo stage IIIA and IIIB showed a hematologic ≧ VGPR rate of 70.0% and 85.0% in the IIIA (n = 20) and IIIB (n = 20) subgroups, respectively. The 2-year OS rates were 74.3% and 65.0% in the IIIA and IIIB subgroups, respectively [14]. Compared with their data, the hematologic response rate and 2-year OS rate in stage IIIA patients were comparable, while stage IIIB patients had inferior outcomes in our study. Another multicenter retrospective study testing daratumumab-bortezomib-cyclophosphamide-dexamethasone in stage IIIB AL (n = 19) showed a 6-month hematologic ≧ VGPR rate of 86.7% and 1-year OS rate of 67.5%, respectively [13], all compared favorably with data in our study (53.8% for hematologic ≧ VGPR rate and 53.8% for 1-year OS rate). In our view, these discrepancies may be linked to the higher tumour burden of dFLC and higher early mortality rate of 46.2% within 6 months (2 COVID-19; 4 sudden cardiac arrests) in our study, which also affected the evaluation of therapeutic efficacy in stage IIIB AL. Also be noted that, the incidence of grade 3 or higher infections was higher in the 4-drug regimen. Overall, our findings suggest that the DVD regimen may also be an effective and tolerable treatment option for patients with Mayo stage IIIB in the first-line setting, potentially representing a step forward in treating this hitherto underserved group of patients.

There is consensus that AL amyloidosis with multiple myeloma has a worse prognosis [18]. Our cohort included 22 patients presented with MDEs, but we found that the presence of MDEs did not affect overall hematologic response rates, likely reflecting high hematologic response rates of DVD therapy. Further studies with a larger patient group are needed to assess the efficacy and safety of the DVD regimen in treating patients with AL amyloidosis and underlying multiple myeloma.

The predominant cytogenetic abnormality t(11;14) is detected in 40–60% of patients with AL amyloidosis [19, 20] and has been shown to negatively impact responses and OS to bortezomib and immunomodulatory-based regimens [19]. In this study, the rates of hematologic CR and ≧ VGPR were unaffected by the presence or absence of t(11;14), and the presence of t(11;14) did not impact OS. These findings are in line with the results of other daratumumab-based frontline therapies [20, 21], suggesting that the use of daratumumab may overcome the adverse impact of t(11;14).

In conclusion, our study demonstrated that the DVD regimen exhibited favorable efficacy and safety in patients with newly diagnosed AL amyloidosis, including those with advanced cardiac involvement. To our knowledge, the present study describes the largest real-world cohort of patients with AL amyloidosis treated upfront with DVD regimen reported so far. The limitations of this study include its retrospective design, relatively short follow-up period, and the lack of response data for some patients. Additionally, some p-values are non-significant but may be underpowered. Further evaluation in prospective clinical trials are warranted to identify which patients benefit most from DVd.

Methods

From January 2022 to October 2025, 64 consecutive patients with newly diagnosed AL amyloidosis who received DVD frontline therapy at Guangdong Provincial People’s Hospital, the First Affiliated Hospital of Jinan University, and Shantou People’s Hospital were included in this retrospectively study. Diagnosis of AL amyloidosis was based on the presence of amyloid-related systemic syndromes, amyloid deposition detected histopathologically in any tissue, restricted LC deposition, and evidence of plasma cell clonality. The amyloid subtype was confirmed by immunoelectron microscopy or by laser capture microdissection and tandem mass spectrometry. The patients were staged according to the 2004 Mayo staging system and 2012 Mayo staging system [22, 23]. Organ involvement was based on the consensus criteria of the International Society of Amyloidosis [24]. Cytogenetics abnormalities were assessed with FISH. The treatment scheme was as follows: intravenous daratumumab at 16 mg/kg weekly in cycles 1–2, every 2 weeks in cycles 3–4, and every 4 weeks in cycles 5–6, then every 4 weeks for up to 2 years, as appropriate; subcutaneous bortezomib at 1.3 mg/m² and dexamethasone at 10–20 mg once weekly for 6 cycles of 28 days each. The hematologic and organ responses to chemotherapy were defined using consensus criteria [24, 25]. Toxicity was assessed and graded according to the Common Terminology Criteria for Adverse Events version 5.0 (NIH, Stapleton, NY). This study was approved by the Ethics Committee of the Guangdong Provincial People’s Hospital (approval no.: KY-Q-2022-063−02) and informed consent was obtained from all patients in accordance with the Declaration of Helsinki.

Continuous variables were summarized using medians and ranges and binary outcomes using proportions. Categorical variables were compared using Chi-squared test or Fisher’s exact. OS was defined as time from treatment initiation to death or last follow-up. Patients who were alive at the time of analysis were censored on the date of the last follow-up. Survival was analyzed using the Kaplan-Meier method and compared between groups using the log-rank test. Statistical tests were performed using SPSS version 27. Two sided p < 0.05 was considered statistically significant.

Abbreviations

AEs

Adverse events

AL

Amyloid light chain

CR

Complete response

Dara-CyBorD

Daratumumab-cyclophosphamide-bortezomib-dexamethasone

DVD

Daratumumab-bortezomib-dexamethasone

dFLC

Difference between involved and uninvolved free light chain

EMA

European Medicines Agency

FDA

Food and Drug Administration

PR

Fluorescence in situ hybridization

LC

Light chain

MDEs

Multiple myeloma defining events

NT-proBNP

N-terminal pro-B-type natriuretic peptide

OS

Overall survival

PR

Partial response

VGPR

Very good partial response

Authors’ contributions

PLL, LYZ, JYW, XD and JHW designed the research; PJL, MYL and SCL participated in the design of the study and performed the research; JHW, PJL and LJZ analyzed the data; JHW, LYZ and PLL performed the statistical analysis; MYL, JQT, PW and PRZ helped to analyze the data; JHW critically assessed the manuscript; PLL revised the manuscript and approved the final version, and all authors read and approved the final manuscript.

Funding

This work was supported by the National Natural Science Foundation of China [Nos. 82100238, 82270161, 82200148]; the Guangdong Basic and Applied Basic Research Foundation [Nos. 2024A1515011063, 2024B1515020054]; Science and Technology Planning Project of Guangdong Province, China (No. 2023B1111050004); the Science and Technology Program of Guangzhou [No. 202201011046]; the High-level Hospital Construction Project of Guangdong Provincial People’s Hospital [Nos. DFJH201923, DFJHBF202107] and the Medical Scientific Research Foundation of Guangdong Province [No.A2019063].

Data availability

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

Declarations

Ethics approval and consent to participate

Informed consent was obtained from all subjects involved in the study.

Competing interests

The authors declare no competing interests.