# New Drugs Plus Chemotherapy for Plasmablastic Lymphoma: What a Major Analysis Found

This meta-analysis combined 12 studies and 410 patients with plasmablastic lymphoma (PBL), a rare and aggressive blood cancer. Researchers found that adding newer drugs — especially bortezomib — to standard chemotherapy improved the objective response rate (56.8% vs. 70.2%) and progression-free survival compared with traditional treatment. Overall survival and rates of serious side effects were similar between the two approaches, but the authors caution that the small sample size means the results should be interpreted carefully.

# New Drugs Plus Chemotherapy for Plasmablastic Lymphoma: What a Major Analysis Found

## Table of Contents

- Key Points
- Background: Why This Research Matters
- How the Research Was Conducted
- How Study Quality Was Assessed
- Key Findings: Response Rates and Survival
- Side Effects and Safety
- Publication Bias and Study Limitations
- What the Results Mean in Context
- Emerging Treatments and Future Directions
- Clinical Implications for Patients
- Recommendations and Actionable Advice
- Limitations: What This Study Could Not Prove
- Conclusion
- Frequently Asked Questions
- Source Information

## Key Points

- In 410 newly diagnosed PBL patients across 12 studies, adding newer drugs — especially bortezomib — to standard chemotherapy improved objective response rate (70.2% vs. 56.8%).
- Progression-free survival was significantly better with new drug combinations (HR 2.22, P < 0.001), but overall survival was not significantly different (HR 1.81, P = 0.41).
- Serious side effects (grade 3–4) were similar between groups (HR 0.85, P = 0.78); adding new drugs did not increase their rate.
- The analysis included mostly retrospective studies and only 410 patients, with high heterogeneity (I² = 95% for objective response rate), so results should be interpreted carefully.
- The authors suggest bortezomib combined with EPOCH or CHOP, plus local radiotherapy as appropriate and ASCT for some high-risk patients, as a more appropriate option for newly diagnosed PBL.

## Background: Why This Research Matters

Plasmablastic lymphoma (PBL) is a rare and highly aggressive type of non-Hodgkin lymphoma (a cancer of the immune system's white blood cells). PBL is known for being resistant to standard drug treatments and for having poor survival rates.

Currently, there is no standard treatment for PBL. Doctors mainly rely on medium- to high-intensity combination chemotherapy (treatment using multiple cancer-killing drugs at once). The most commonly used regimens come from treatments developed for HIV-related non-Hodgkin lymphoma.

These traditional regimens include:

-
**CHOP** — cyclophosphamide, doxorubicin, vincristine, and prednisone
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**EPOCH** — etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin
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**hyper-CVAD-MA** — cyclophosphamide, vincristine, doxorubicin, dexamethasone, plus high-dose methotrexate and cytarabine
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**CODOX-M/IVAC** — a combination regimen used in aggressive lymphomas

The National Comprehensive Cancer Network (NCCN) Guidelines, version 2024.1, recommend using regimens stronger than CHOP for PBL. However, even with these stronger treatments, outcomes remain poor.

To improve treatment results and overcome drug resistance, researchers are urgently investigating newer drugs. These include **bortezomib**, **lenalidomide**, and **ixazomib**. However, randomized controlled trials (the gold-standard type of clinical study) for these drugs in PBL are very limited.

This is why the authors conducted a systematic review and meta-analysis. A meta-analysis combines data from multiple studies to produce a more powerful overall result. The goal was to compare the effectiveness, survival outcomes, and safety of combining new drugs (such as bortezomib) with traditional regimens. Traditional regimens include EPOCH, CHOP-like regimens, and/or radiation therapy. The comparison was in patients newly diagnosed with PBL.

## How the Research Was Conducted

The researchers followed strict, internationally recognized methods for conducting a systematic review. The study was registered with PROSPERO (an international database of systematic reviews) under registration number CRD42024578897.

**Which studies were included?** The researchers included studies that met all of the following criteria:

1. Prospective randomized controlled trials (RCTs) or retrospective analyses (studies looking back at patient records) from domestic and international sources
1. Patients newly diagnosed with PBL
1. All PBL diagnoses confirmed by histopathologic examination (microscopic tissue analysis) and immunohistochemistry (IHC) studies (tests that identify specific proteins on cells)
1. A minimum of 10 patients in the study
1. The study reported treatment outcomes such as response rate, progression-free survival, or overall survival

**Which studies were excluded?** The researchers excluded:

- Articles where the full text could not be obtained
- Literature reviews and conference papers
- Studies with incomplete information for data extraction
- Studies that had been published more than once (duplicate publications)

**Where did they search?** The researchers searched PubMed, Embase, Medline, Web of Science, the Cochrane Central Register of Controlled Trials, the Cochrane Library, the Science Citation Index, and conference abstracts. The search cut-off date was August 2024. Keywords included "plasma cell lymphoma," "plasmablastic lymphoma," "treatment," and "management." No language restrictions were applied.

**How was data collected?** Two reviewers (Guo and Quan) independently extracted data from each included study. They collected information on the first author, publication journal, year of publication, number of patients in each group, average age, treatment regimen, effectiveness, and adverse reactions. Any disagreements were resolved through discussion or third-party evaluation.

**How were patients grouped?** Based on whether treatment included new drugs, patients were divided into two subgroups:

-
**Subgroup 1:** Traditional treatment versus no treatment
-
**Subgroup 2:** Traditional treatment versus a combination of new drugs plus traditional treatment

**What outcomes were measured?** The study tracked four main outcomes:

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**Objective response rate (ORR)** — the proportion of patients who achieved complete remission (CR, no detectable cancer) or partial remission (PR, significant reduction in cancer) among all patients eligible for assessment. This was evaluated using the Lugano 2014 criteria.
-
**Progression-free survival (PFS)** — the time from starting treatment to the first recurrence, progression, death, or last follow-up for any reason
-
**Overall survival (OS)** — the time from starting treatment to death or last follow-up for any reason
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**Grade 3 or higher adverse events (AE)** — serious side effects, assessed according to the Common Terminology Criteria for Adverse Events (CTCAE)

**How was the statistical analysis performed?** The researchers used RevMan 5.4 software. When significant statistical heterogeneity existed among studies (I² > 50%, P < 0.1), they used a random-effects model. When studies were homogeneous (I² ≤ 50%, P ≥ 0.1), they used a fixed-effects model. Mean difference (MD) and its 95% confidence interval (CI) were used for quantitative data, and relative risk (RR) was used for count data. A P-value less than 0.05 indicated a statistically significant difference. Funnel plots were used to assess publication bias.

## How Study Quality Was Assessed

Two reviewers used the Newcastle–Ottawa Scale (NOS) to evaluate the quality of each included study. The NOS assesses three areas:

-
**Selection of study subjects** — scored 0 to 4 points
-
**Comparability** — scored 0 to 2 points
-
**Exposure or outcome assessment** — scored 0 to 3 points

The maximum NOS score was 9 points. Studies scoring 6 or higher were considered high quality, while scores below 4 were considered low quality. The two reviewers agreed on over 80% of the quality assessment items. When they disagreed, they held discussions or consulted with experts. All included studies scored between 6 and 8 points, meaning all were classified as high-quality studies.

The researchers also used the Cochrane bias risk assessment criteria to evaluate potential bias in the included studies.

## Key Findings: Response Rates and Survival

The researchers retrieved a total of 1,603 articles from their searches (PubMed: 664, Embase: 907, Cochrane Central Database: 20, Clinical Trials: 3, Wan Fang: 9). After removing duplicate articles, reviews, and conference abstracts, they screened titles and abstracts. Finally, they included 12 articles after reading the full text, covering a total of 410 patients with PBL.

Of the 12 included studies, 11 were retrospective studies and 1 was a randomized controlled trial.

**Patient groups:**

-
**Subgroup 1** included 152 patients who received traditional regimens (EPOCH, CHOP-like regimens, and/or local radiotherapy) and 30 patients in the control group who received no treatment. Patients who received only palliative (comfort-focused) care did so because of older age at diagnosis, poor performance status, co-morbidities (other health conditions), or because they could not tolerate chemotherapy. Some patients who were HIV-positive had received anti-retroviral therapy (ART) alone.
-
**Subgroup 2** included 115 patients who received traditional regimens and 44 patients who received traditional regimens combined with new drugs (bortezomib, lenalidomide, or CAR-T therapy).

**Objective response rate (ORR):** Among patients eligible for efficacy assessment, the ORR was higher in the combined new drug group than in the traditional treatment group. The rates were **56.8% (25 out of 44 patients)** in the traditional treatment group versus **70.2% (66 out of 94 patients)** in the combined new drug group. The odds ratio (OR) was 2.18, with a 95% confidence interval of 1.58 to 2.78, and P = 0.002. Because this P-value is less than 0.05, the difference was statistically significant. However, heterogeneity among study results was very high at I² = 95%, meaning the studies varied considerably in their results.

**Progression-free survival (PFS):** Four studies used hazard ratios (HR) to assess OS and PFS. The progression-free survival rate was better in the combined new drug group compared with the traditional treatment group. The hazard ratio was 2.22, with a 95% confidence interval of 1.71 to 2.90, and P < 0.001. This result was statistically highly significant.

**Overall survival (OS):** There was no statistically significant difference between the two groups in overall survival. The hazard ratio was 1.81, with a 95% confidence interval of 0.44 to 7.46, and P = 0.41. Because the P-value is greater than 0.05, this difference was not statistically significant.

**Follow-up and outcomes across studies:** The included studies reported varying follow-up periods and outcomes:

- Jorge Castillo (2008): 112 patients, 19-month follow-up, overall survival 15 months, mortality rate 29 out of 55 patients (53%)
- Yusuke Koizumi (2016): 24 patients, 15-month follow-up, PFS 13 months, OS 15 months
- Ariela Noy (2016): 12 patients, 73-week follow-up (range 40–165 weeks), OS 11.6 months (range 2–63 months)
- Brenda Mai (2020): 21 patients, 19-month follow-up (range less than 1 to 112 months), OS 4.7 months, mortality rate 9 out of 16 patients (75%)
- A. H. Rudresha (2020): 13 patients, 33-month follow-up, OS 9 months, mortality rate 6 out of 13 patients (46%)
- Jayachandran Perumal Kalaiyarasi (2020): 25 patients, 26.9-month follow-up (range 0.3–34.1 months), PFS 5.9 months, OS 12.4 months
- Nadine Rapiti (2022): 26 patients, 78-month follow-up, PFS 8 months (range 1–97 months), OS 16 months (range 1–111 months)
- Christopher Dittus (2018): 8 patients, 48-month follow-up, PFS 10.8 months (range 0.73–77.8 months), OS 10.8 months (range 0.73–77.8 months)
- Fu Weijia (2020): 15 patients, 30.3-month follow-up (range 4.8–61.1 months), PFS 6.8 months (range 2.5–11.1 months), OS 17.9 months (range 5.6–30.2 months), mortality rate 8 out of 15 patients (53%)
- Rehan Jessa (2022): 42 patients, 96-month follow-up, PFS 8 months, OS 15 months
- Brian T. Hess (2023): 80 patients, 34-month follow-up (range 1–196 months), PFS rate 72% (95% CI 62–83%), OS rate 79% (95% CI 70–89%)
- Ning Dong (2023): 32 patients, 77.6-month follow-up, PFS 6.7 months (range 3.4–8.3 months) versus not reached, OS 14.7 months (range 10.2–33.7 months) versus 89.1 months (range 56.7 months to not available)

## Side Effects and Safety

Among 159 patients eligible for safety assessment, there was no significant difference in grade 3–4 adverse events (serious side effects) between the two groups. The hazard ratio was 0.85, with a 95% confidence interval of 0.27 to 2.71, and P = 0.78. Because the P-value is greater than 0.05, this difference was not statistically significant.

This means that adding new drugs to traditional treatment did not increase the rate of serious side effects. The authors noted that combination treatment for PBL can cause adverse reactions such as neurotoxicity (nerve damage). However, the results of this meta-analysis are consistent with known reports about adverse reactions, and the new drugs did not increase the incidence of adverse events.

## Publication Bias and Study Limitations

The researchers used funnel plots to assess publication bias (the tendency for studies with positive results to be published more often than studies with negative results). They concluded that the included studies may have publication bias due to the nature of the original data. The local areas on the funnel plot may be irregular, but overall there was no significant publication bias.

The risk of bias assessment used the Cochrane criteria and the Newcastle–Ottawa Scale. All included studies scored between 6 and 8 points on the NOS. This classified all included studies as high-quality studies.

## What the Results Mean in Context

This meta-analysis included 11 retrospective studies and 1 randomized controlled trial. It compared the efficacy, survival, and safety of new drug combinations with traditional regimens in 410 newly diagnosed PBL patients. According to the authors, no systematic reviews had previously compared new and traditional therapies for PBL, making this analysis important for clinical practice.

The results showed that compared with traditional regimens, new drug combination regimens significantly improved ORR and PFS in newly diagnosed PBL. Overall survival and adverse reactions were similar between the two groups.

The new drugs studied include bortezomib, rituximab, lenalidomide, hematopoietic stem cell transplantation (autologous and allogeneic), and CAR-T therapy. Among these, **bortezomib** is the most widely used and has shown significant efficacy.

**What is PBL?** PBL was first discovered in 1997 by Delecluse and colleagues. The exact cause of PBL is currently unclear, but it may be related to viral infection. PBL originates from plasmablasts, which are activated B cells (a type of immune cell). These activated B cells have undergone somatic hypermutation and class switch recombination. Somatic hypermutation and class switch recombination are genetic changes that occur as B cells mature.

According to relevant literature, the median overall survival of PBL patients is 15 months, and the 3-year overall survival rate is 25%.

**Supporting evidence from other studies:**

- Barta and colleagues studied 93 cases of HIV-related PBL and found that the EPOCH regimen showed significant advantages in complete remission, PFS, and OS compared to the CHOP regimen.
- Castillo and colleagues used EPOCH combined with bortezomib in 16 newly diagnosed PBL patients. Fifteen patients achieved complete remission and 1 achieved partial remission.
- A multicenter study in the United States showed that consolidation radiotherapy (radiation given after chemotherapy to prevent recurrence) in early PBL can improve outcomes. Chemotherapy combined with radiotherapy showed significantly improved 3-year PFS (85% vs. 65%) and OS (96% vs. 71%) compared to chemotherapy alone.
- Cattaneo and colleagues followed 24 newly diagnosed PBL patients for 10 years. Of these, 67% underwent autologous hematopoietic stem cell transplantation (ASCT, using the patient's own stem cells) after first-line therapy. Fifty percent achieved complete remission, 17% achieved partial remission, and the 2-year recurrence rate was 30%.

In 2024, Ramirez-Gamero and colleagues reviewed the diagnosis, risk stratification, and treatment of plasma cell lymphoma. They recommended EPOCH with or without bortezomib for PBL patients, with the option of combining local radiotherapy and ASCT for high-risk patients.

This meta-analysis systematically analyzed the data and concluded that chemotherapy regimens combining bortezomib — such as V-EPOCH or V-CHOP — are effective for newly diagnosed PBL. In the study by Fu Weijia and colleagues, 1 case achieved complete remission with combined bortezomib and lenalidomide in first-line treatment. When the disease recurred, 1 case achieved remission again with bortezomib combined with ixazomib.

Compared with traditional treatment regimens, bortezomib-based combination chemotherapy significantly improved ORR and PFS in newly diagnosed PBL. This is consistent with previous reports.

Additionally, patients who underwent ASCT included 1 patient in the study by Fu Weijia and colleagues, 8 patients in the study by Brian T. Hess and colleagues, 9 patients in the study by Ning Dong and colleagues, and 3 patients in the study by Rehan Jessa and colleagues. Patients who underwent local radiotherapy included 29 patients in the study by Brian T. Hess and colleagues and 10 patients in the study by Ning Dong and colleagues. These additional treatments further improved efficacy.

Based on these findings, the authors suggest a treatment regimen of bortezomib combined with EPOCH or CHOP regimens. The regimen should be combined with local radiotherapy as appropriate. The regimen should include ASCT for some high-risk patients. This regimen is a more appropriate option for newly diagnosed PBL.

## Emerging Treatments and Future Directions

Among the included studies, only one study compared outcomes of PBL patients who were HIV-positive versus HIV-negative. Other studies included only HIV-positive patients, only HIV-negative patients, or did not provide comparative descriptions. This means the meta-analysis lacks a comparison of efficacy between HIV-positive and HIV-negative patients, which may add bias to the results.

About 30% of PBL cases express CD30 (a protein found on certain cancer cells). Brentuximab vedotin is a drug that targets CD30. Some researchers have explored targeted therapy for PBL using this drug. Holderness and colleagues reported 1 case of a patient with chronic lymphocytic leukemia (CLL) whose disease partially transformed to PBL. The disease progressed after chemotherapy and radiotherapy. The patient received brentuximab vedotin treatment, and the tumor size significantly reduced.

Studies have shown that PD-1 and PD-L1 (proteins that help cancer cells evade the immune system) are also overexpressed and have biological activity in PBL. One case of an early relapsed elderly PBL patient achieved complete remission with pembrolizumab (an immunotherapy drug) plus radiotherapy.

CAR-T therapy (a treatment that genetically modifies a patient's own immune cells to attack cancer) for PBL is another research direction. Raghunandan and colleagues reported a case of a young patient who developed PBL after receiving immunotherapy and anti-CD19 CAR-T therapy for acute lymphoblastic leukemia. For PBL, the patient received bortezomib and chemotherapy, followed by allogeneic stem cell transplantation (using donor stem cells). When PBL relapsed, combined chemotherapy regimens containing daratumumab were ineffective. The patient remained in complete remission for 14 months after CAR-T therapy.

Other exploration directions for PBL include newly developed drugs for diffuse large B-cell lymphoma (DLBCL) or multiple myeloma. These include venetoclax, selinexor, elotuzumab, CELMODS, and PGRCD5 bispecific antibodies.

## Clinical Implications for Patients

This meta-analysis provides important information for patients and their families facing a PBL diagnosis. The key takeaway is that adding newer drugs — especially bortezomib — to standard chemotherapy may improve the chance of responding to treatment and extend the time before the cancer progresses.

Specifically, the study found that:

- Patients receiving new drug combinations had a higher objective response rate (70.2% vs. 56.8%)
- Progression-free survival was significantly better with new drug combinations (HR = 2.22, P < 0.001)
- Overall survival was not significantly different between the two groups (HR = 1.81, P = 0.41)
- Serious side effects (grade 3–4) were not significantly different between the two groups (HR = 0.85, P = 0.78)

These findings suggest that bortezomib-based combination regimens, such as V-EPOCH or V-CHOP, may be a better first-line treatment option for newly diagnosed PBL. Adding local radiotherapy when appropriate and considering ASCT for high-risk patients may further improve outcomes.

## Recommendations and Actionable Advice

Based on the findings of this meta-analysis, the following recommendations may be relevant for patients and their care teams:

1.
**Discuss bortezomib-based regimens with your oncologist.** The study found that combining bortezomib with EPOCH or CHOP regimens improved response rates and progression-free survival compared with traditional chemotherapy alone.
1.
**Ask about local radiotherapy.** For patients with early-stage PBL, adding radiotherapy after chemotherapy may improve outcomes. One study showed 3-year PFS of 85% with combined treatment versus 65% with chemotherapy alone.
1.
**Consider stem cell transplantation if you are high-risk.** Autologous hematopoietic stem cell transplantation (ASCT) may be an option for some high-risk patients after first-line therapy.
1.
**Be aware that serious side effects were similar.** The study found no significant increase in grade 3–4 adverse events when new drugs were added to traditional treatment.
1.
**Understand the limitations.** The small sample size of this study increases the possibility of bias. Discuss the results with your medical team and consider them alongside your individual situation.

## Limitations: What This Study Could Not Prove

The authors identified several important limitations of their study:

-
**Small sample size:** The analysis included only 410 patients across 12 studies. This increases the possibility of bias, and the results need to be treated with caution.
-
**Mostly retrospective studies:** Eleven of the 12 included studies were retrospective (looking back at existing records), with only 1 randomized controlled trial. Retrospective studies are generally considered weaker evidence than prospective randomized trials.
-
**High heterogeneity:** The heterogeneity among study results was very high (I² = 95% for ORR), meaning the studies varied considerably in their findings.
-
**Lack of HIV comparison:** Only one study compared outcomes between HIV-positive and HIV-negative patients. This may add bias to the results.
-
**Insufficient data for finer classification:** There was not enough data to analyze newly diagnosed versus relapsed/refractory patients, different age groups, or different disease stages separately.
-
**No standard treatment exists:** Because there is no standard treatment for PBL, comparing different regimens across studies is challenging.

The authors concluded that further analysis is needed for newly diagnosed, relapsed/refractory, age, and stage subgroups. The impact of these treatments on the prognosis of PBL patients still needs further exploration.

## Conclusion

The results of this meta-analysis suggest that using new drugs — especially bortezomib — in the treatment of newly diagnosed PBL may improve patient response rates and survival. The adverse reactions were similar to those of traditional regimens.

However, the study has certain limitations. All included patients were newly diagnosed with PBL, most studies were retrospective case analyses, and there was not enough data for finer classification. Further analysis is needed for newly diagnosed, relapsed/refractory, age, and stage subgroups. The impact on the prognosis of PBL patients still needs further exploration.

Despite these limitations, this meta-analysis represents the first systematic comparison of new drug combinations versus traditional regimens for PBL. It provides valuable guidance for clinical practice and highlights the potential of bortezomib-based regimens as a more effective treatment option for this rare and aggressive cancer.

## Frequently Asked Questions

### What is plasmablastic lymphoma (PBL)?

PBL is a rare and highly aggressive type of non-Hodgkin lymphoma, a cancer of the immune system's white blood cells. It is known for being resistant to standard drug treatments and for poor survival rates. There is currently no standard treatment for PBL, so doctors rely on medium- to high-intensity combination chemotherapy regimens.

### What did this analysis find about adding new drugs to chemotherapy for PBL?

In 410 newly diagnosed PBL patients across 12 studies, adding newer drugs — especially bortezomib — to standard chemotherapy improved the objective response rate (70.2% vs. 56.8%) and progression-free survival compared with traditional treatment. Overall survival and rates of serious side effects were similar between the two approaches.

### What does objective response rate mean in this context?

Objective response rate is the proportion of patients who achieved complete remission (no detectable cancer) or partial remission (significant reduction in cancer) among all patients eligible for assessment. In this analysis, it was 70.2% with new drug combinations versus 56.8% with traditional treatment.

### Did adding new drugs increase serious side effects?

Among 159 patients eligible for safety assessment, there was no significant difference in grade 3–4 adverse events between the two groups (HR 0.85, P = 0.78). Adding new drugs to traditional treatment did not increase the rate of serious side effects. Combination treatment for PBL can cause neurotoxicity, but the new drugs did not increase adverse events.

### What are the limitations of this analysis?

The analysis included only 410 patients across 12 studies, mostly retrospective, which increases the possibility of bias. Heterogeneity was very high (I² = 95% for objective response rate). Only one study compared HIV-positive and HIV-negative patients, and there was not enough data to analyze subgroups by age, stage, or relapsed/refractory status.

### What treatment options does this analysis suggest for newly diagnosed PBL?

The authors suggest bortezomib combined with EPOCH or CHOP regimens (such as V-EPOCH or V-CHOP) as a more appropriate option for newly diagnosed PBL. They also note that local radiotherapy may be added as appropriate, and autologous stem cell transplantation may be considered for some high-risk patients after first-line therapy.

### What is the typical outlook for PBL?

According to relevant literature cited in the analysis, the median overall survival of PBL patients is 15 months, and the 3-year overall survival rate is 25%. However, the analysis found that adding newer drugs, especially bortezomib, to standard chemotherapy improved response rates and progression-free survival in newly diagnosed patients.

### When should a patient with newly diagnosed plasmablastic lymphoma seek a second opinion?

Plasmablastic lymphoma has no standard treatment, and this analysis of 410 patients found that adding bortezomib to regimens such as EPOCH or CHOP improved response rates (70.2% vs. 56.8%) and progression-free survival, while overall survival and serious side effects were similar. Because most included studies were retrospective, the sample was small, and heterogeneity was high, a second opinion can help confirm the diagnosis and weigh bortezomib-based regimens, radiotherapy, or stem cell transplantation for high-risk disease. Diagnostic Detectives Network provides independent expert second opinions.

## Source Information

**Original article title:** Meta-analysis of the comparative efficacy and safety of new drugs in combination with chemotherapy in primary plasmoblastic lymphoma.

**Authors:** Bingling Guo, Xi Quan, Zailin Yang, Jieping Li, Yao Liu

**Affiliation:** Department of Hematology-Oncology, Chongqing University Cancer Hospital, No. 181 HanYu Road, Chongqing 400030, China

**Journal:** Clinical and Experimental Medicine (2025) 25:103

**DOI:** https://doi.org/10.1007/s10238-025-01636-9

**Publication dates:** Received 25 September 2024; Accepted 14 March 2025; Published online 1 April 2025

**Funding:** Natural Science Foundation of Chongqing, China (2023NSCQ-MSX3180); Key Project of Chongqing Technology Innovation and Application Development Special Project (CSTB2024TIAD-KPX0031); and 2025 Chongqing Science and Health Joint Medical Research (2025DBXM002)

**PROSPERO registration number:** CRD42024578897

*This patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and should not replace consultation with a qualified healthcare professional. Patients should discuss their individual treatment options with their medical team.*


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