Global trends in CAR-T cell therapy for multiple myeloma: A bibliometric analysis, 2013-2025.

Introduction

Multiple myeloma (MM) is the second most common hematological malignancy globally. In 2022, there were approximately 188,000 new cases and 121,000 deaths attributed to MM worldwide. Projections indicate that by 2045, the incidence and mortality rates will increase by 71% and 79%, respectively, compared to 2022, posing a substantial burden on the global healthcare system. 1 Despite advancements in treatment – such as proteasome inhibitors, immunomodulatory drugs, anti-CD38 monoclonal antibodies, and autologous stem cell transplantation – that have significantly extended the median survival of MM patients, relapse and drug resistance remain critical clinical challenges that ultimately contribute to patient mortality. 2 , 3 CAR-T cell therapy, representing an innovative immunotherapeutic approach, involves the genetic modification of T cells to express receptors that specifically target and recognize tumor cells, thereby facilitating precise tumor cell eradication. This therapy offers renewed hope for patients with relapsed or refractory MM (R/R MM).

Recent advancements in the treatment of MM using CAR-T cells have seen a significant surge in research activity. It is crucial to elucidate global research trends and identify core hotspots within this domain to address clinical treatment challenges and facilitate the translation of research into clinical practice. Given the rapid expansion of publications, clinical research, and emerging targets in recent years, a timely bibliometric map is needed to quantitatively clarify the evolving research landscape of CAR-T therapy in MM. This method, in contrast to narrative reviews, offers an objective means to identify publication trends, collaborative networks, research hotspots, and emerging topics within this rapidly advancing field. By quantitatively examining publication trends, key authors, research institutions, keyword clustering, and other relevant metrics, bibliometrics provides a scientific foundation for researchers to select pertinent topics, gain a comprehensive understanding of the field, identify emerging directions, and optimize resource allocation. 4

Although bibliometric studies have explored CAR-T cell therapy in solid tumors and hematological malignancies broadly, 5 , 6 these analyses encompassed diverse disease entities – such as solid tumors, leukemia, lymphoma, and MM – without disease-specific stratification. In particular, the seminal bibliometric study by Huang et al. 6 aggregated all subtypes of hematological malignancies, including leukemia, lymphoma, and myeloma, into a single analysis, which precluded the extraction of research trends and evolutionary patterns specific to MM. In contrast, our study rigorously confines the scope of analysis to CAR-T cell therapy specifically for MM, thereby eliminating confounding influences from other hematologic malignancies. Furthermore, we extend the dataset timeline to the end of 2025 and identify two novel, cutting-edge research directions – GPRC5D-CAR-T and off-the-shelf allogeneic CAR-T – that were not addressed in previous comprehensive hematology bibliometric studies. These methodological enhancements provide precise and up-to-date quantitative insights that are not available in earlier broad-spectrum analyses. This MM-specialized bibliometric analysis is underpinned by three fundamental rationales. Firstly, MM possesses unique CAR-T targets, toxicity profiles, and mechanisms of antigen escape resistance that are distinct from those observed in leukemia and lymphoma, and thus cannot be adequately distinguished within generalized pan-hematology bibliometric studies. Secondly, the recent landmark approvals of BCMA-CAR-T therapies necessitate a comprehensive and updated quantitative analysis. Thirdly, bibliometric visualization provides an objective mapping of collaborative networks and emerging trends, offering insights that traditional reviews are unable to quantify. This study concentrates on CAR-T cell therapy for MM, aiming to systematically analyze trends in research output, identify principal contributors and collaborative networks, uncover research hotspots along with their temporal evolution, and discuss potential breakthroughs and future directions. The ultimate aim is to furnish quantifiable evidence and targeted research guidance for future basic and clinical investigations in this rapidly evolving field.

Materials and methods

Data collection and search strategies

This study sourced literature data from the Web of Science Core Collection (WoSCC) database. The search was performed on January 26, 2026 (retrospective coverage from January 1, 2013 to December 31, 2025). The search formula was constructed as follows:

#1 : TS = (CAR-T OR “chimeric antigen receptor T*” OR “chimeric antigen receptor modified T” OR “chimeric antigen receptor transduced T” OR “chimeric antigen receptor engineered T” OR “chimeric antigen receptor redirected T”);

#2 : TS = (“multiple myeloma*” OR “plasma cell myeloma*” OR “Kahler Disease”);

#3 : #1 AND #2.

The inclusion criteria were: (a) studies addressing the intersection of CAR-T cell therapy and MM; (b) publications within the predefined time span from January 1, 2013, to December 31, 2025; (c) English-language publications; and (d) publication types limited to articles and reviews. The exclusion criteria were: (a) literature with irrelevant topics, specifically those addressing only a single aspect of CAR-T cell therapy or MM, and those not encompassing both; and (b) non-target publication types, including conference abstracts, books, letters, editorials, and other non-article or non-review records. The process of duplicate removal was executed utilizing the deduplication module of CiteSpace 6.2.R1. The criteria for identifying duplicates included the complete title, the full name of the first author, the year of publication, and the source journal title. Records sharing identical criteria were identified as duplicates, with only one original record retained. Following a thorough software inspection, no duplicate documents were detected.

The specific parameters used for bibliometric analysis were as follows. CiteSpace 6.2.R1 was employed with the following settings: time slicing from 2013 to 2025 with 1‑year increments; node types including countries, institutions, authors, keywords, and cited references; selection criteria based on the g‑index (k = 25); LRF = 2.5; L/N = 10; LBY = 5; e = 1.0; Pruning: Pathfinder. VOSviewer 1.6.17 was used for co‑authorship, co‑occurrence, and journal density visualization, with default parameters: full counting method; minimum number of occurrences for keywords set to 20; the minimum number of documents per author was set to 7; visualization type: density map for journals and keywords; visualization weights: occurrences; Max. length: 30; and Font: open scans.

In cases of discrepancies during the screening process, consensus was reached through consultation with a third researcher. Following de-duplication using bibliometric software, a total of 1,661 eligible documents, comprising 874 articles and 787 reviews, were identified. The literature search process is illustrated in Figure 1 . Detailed step-by-step retrieval counts are also provided in Supplementary Table S1 for reference. It should be noted that all bibliometric analyses were conducted using the entire dataset of 1,661 documents, including both articles and reviews.

The literature search process of this study.

A total of 1,661 documents (including 874 articles and 787 reviews) were finally included based on the retrieval strategy.

Data analysis and visualization

This study employed CiteSpace 6.2.R1 and VOSviewer 1.6.17 to conduct bibliometric and visual analysis of the data. CiteSpace facilitates an in-depth exploration of latent information within the literature and provides precise analyses of research hotspots and developmental trends in this field; VOSviewer is capable of effectively building domain knowledge maps and visually displaying the comprehensive research landscape. 7 , 8

Results

The analysis of annual publication volume trends

The analysis included a total of 1,661 documents (including 874 articles and 787 reviews) based on the retrieval strategy. As illustrated in Figure 2 , the annual publication volume within this field exhibits a significant upward trend, which can be categorized into three distinct phases: the period from 2013 to 2015 represents a steady inception phase, characterized by the publication of only 2 to 7 documents per year, indicating an initial exploratory stage of research; the years 2016 to 2019 mark a phase of gradual growth, with annual publication numbers rising from 22 to 67, reflecting increasing attention to the field; and the period from 2020 to 2025 signifies a phase of rapid expansion, with annual publication numbers escalating from 111 to 377, reflecting a marked increase in academic output during this period. The linear regression analysis (Figure S1) reveals a strong linear correlation between the number of published documents and time (Y = 32.31X − 65,113, R 2  = 0.8989, p  < .0001), demonstrating a high goodness of fit. Based on this linear regression model, the historical data show an average annual increase of approximately 32 documents over the study period (2013–2025). Furthermore, the citation frequency has exhibited exponential growth, escalating from 7 citations in 2013 to an estimated 16,998 in 2025, culminating in a total of 53,482 citations.

Annual publication trends in CAR-T cell therapy for MM from 2013 to 2025.

The blue dashed line and bars indicate the number of publications per year, showing exponential growth from 2 documents in 2013 to 377 in 2025. The red solid line represents total annual citations, increasing dramatically from 7 to 16,998, demonstrating rising academic impact.

The analysis of countries and institutions

At the national level, as illustrated in Table 1 , the United States holds a predominant position, with 802 published documents, substantially surpassing other countries. China ranks second with 372 documents, indicating high research activity within this field. Germany (n = 171), Italy (n = 131), and Spain (n = 129) follow in succession. Notably, Russia (centrality = 0.78), Saudi Arabia (centrality = 0.66), and Croatia (centrality = 0.45) exhibit high intermediary centrality, suggesting that these countries play a crucial role as bridges within the international collaboration network. However, it should be noted that high centrality reflects network connectivity rather than scientific leadership or direct clinical impact.

Table 1. The top 10 countries and institutions in terms of publishing volume. Rank country Documents Centrality Institution Documents Centrality 1 United States 802 0 Harvard University 129 0 2 China 372 0.05 Mayo Clinic 105 0.06 3 Germany 171 0.1 Memorial Sloan Kettering Cancer Center 105 0.21 4 Italy 131 0 University of California System 92 0.01 5 Spain 129 0.05 Dana-Farber Cancer Institute 85 0 6 France 85 0.1 University of Pennsylvania 78 0.01 7 United Kingdom 76 0.16 University of Texas System 78 0.2 8 Netherlands 59 0.2 Icahn School of Medicine at Mount Sinai 67 0.2 9 Belgium 56 0 UTMD Anderson Cancer Center 63 0 10 Canada 56 0.1 Fred Hutchinson Cancer Center 61 0.04         University of Wurzburg 61 0.01

The top 10 countries and institutions in terms of publishing volume.

At the institutional level, as presented in Table 1 , Harvard University is ranked first with 129 documents, whereas both Mayo Clinic and Memorial Sloan Kettering Cancer Center are tied for second place with 105 documents each. This underscores the prominent role of leading scientific research institutions in this domain. Furthermore, Figure 3 corroborates the extensive and close collaboration between countries and institutions, highlighting the highly internationalized nature of research activities in this field.

Co-occurrence network visualization of countries (A) and institutions (B) in CAR-T cell therapy for MM.

The country collaboration network shows the USA (802 documents) and China (372) as the leading contributors, with node size representing publication volume and colors indicating temporal evolution from 2013 (purple) to 2025 (red). (B) The institutional network highlights Harvard University (129), Mayo Clinic (105), and Memorial Sloan Kettering Cancer Center (105) as the most productive institutions.

The analysis of journals

As illustrated in Table 2 , Frontiers in Immunology emerged as the leading journal with 87 documents, followed by Cancers with 68 documents. Figure 4(A) shows these high-volume journals intuitively and reveals that they are mainly concentrated in the core research directions such as immunotherapy, hematology, and oncology. In terms of citation frequency, the New England Journal of Medicine ranked first with 5,037 citations. It is followed by Nature Reviews Clinical Oncology (n = 2,754) and Blood (n = 2,725) (see Table 2 ).

Table 2. The top 10 journals in terms of publication volume or citation frequency. Rank Journals Documents Journals Citations 1 Frontiers in Immunology 87 New England Journal of Medicine 5037 2 Cancers 68 Nature Reviews Clinical Oncology 2754 3 Blood Advances 49 Blood 2725 4 Frontiers in Oncology 46 Frontiers in Immunology 2475 5 Transplantation and Cellular Therapy 44 Journal of Clinical Oncology 1802 6 Clinical Lymphoma Myeloma & Leukemia 34 Journal of Hematology & Oncology 1774 7 International Journal of Molecular Sciences 34 Blood Advances 1687 8 Blood 31 Nature Medicine 1482 9 Blood Cancer Journal 29 Molecular Therapy 1310 10 Journal for Immunotherapy of Cancer 25 Signal Transduction and Targeted Therapy 1303

The top 10 journals in terms of publication volume or citation frequency.

Density visualization of journals (A) and co-authorship network of authors (B) in CAR-T cell therapy for MM.

(A) The density visualization map of journals that have published literature on CAR-T cell therapy for MM. Areas with higher density indicate journals with a greater volume of publications in this field. (B) The collaboration network map of authors involved in CAR-T cell therapy for multiple myeloma research. Each node represents an author, with node size reflecting the number of publications. Lines between nodes indicate collaborative relationships, and different colors represent distinct research clusters.

The analysis of authors

The literature encompassed in this study was collaboratively produced by 8,169 researchers worldwide. Analysis of the publication frequency reveals that Hermann Einsele leads with 38 documents, followed by Sundar Jagannath with 30 documents, and Saad Z. Usmani with 27 documents ( Table 3 ). The visualization of the collaborative network in Figure 4(B) illustrates the formation of several closely coordinated research clusters within this field. These clusters predominantly comprise international research teams centered in Europe and the United States, as well as local research teams characterized by Chinese attributes.

Table 3. The top 10 authors ranked by the number of documents or citation count. Rank Author Documents Rank Cited author Citations 1 Hermann Einsele 38 1 James N. Kochenderfer 5445 2 Sundar Jagannath 30 2 Marcela V. Maus 2365 3 Saad Z. Usmani 27 3 Sundar Jagannath 2266 3 Kailin Xu 27 4 Carl H. June 2082 4 He Huang 26 5 Adam D. Cohen 2048 5 Zhenyu Li 25 6 Yi Lin 2024 5 Niels W. C. J. Van De Donk 25 7 Deepu Madduri 1980 6 Yongxian Hu 24 8 Kristen Hege 1784 7 Hai Cheng 22 9 Noopur Raje 1779 7 Adam D. Cohen 22 10 Michaela Liedtke 1665 7 Nina Shah 22       8 Jiang Cao 20       9 Wei Chen 19       9 Yi Lin 19       9 Sham Mailankody 19       10 Binod Dhakal 18

The top 10 authors ranked by the number of documents or citation count.

A detailed examination of citation frequency reveals that James N. Kochenderfer is the most frequently cited author, followed by Marcela V. Maus (n = 2,365), Sundar Jagannath (n = 2,266), and Carl H. June (n = 2,082) ( Table 3 ). These authors accumulate the highest citation counts in the co-citation analysis, reflecting that their published works are frequently referenced by subsequent studies in this domain.

The analysis of keywords

Following data cleaning, synonym consolidation, and standardization processes, a total of 3,788 keywords pertinent to CAR-T cell therapy for MM were identified in this study. Figure 5(A) offers an intuitive depiction of high-frequency keywords, specifically those appearing more than 50 times. Table 4 presents the top 20 high-frequency keywords, with “MM” (n = 856) ranking first, thereby clearly defining the core research focus. “CAR-T” (n = 668) and “immunotherapy” (n = 522) form the foundational technological framework, underscoring the primary trajectory of research in this field. “BCMA” (n = 225) emerges as a significant target, while keywords such as “dexamethasone,” “CRS,” “efficacy,” “management,” “bispecific antibody,” “bortezomib,” “lenalidomide,” and “daratumumab” frequently appear. This suggests that clinical efficacy evaluation, adverse reaction management, and combination therapy strategies constitute frequently addressed themes in the current literature.

The co-occurrence density map (A) and network map (B) of keywords in the field of CAR-T cell therapy for MM.

(A) Density visualization of keyword co-occurrence. Areas with higher density represent higher frequency and stronger co-occurrence relationships among keywords, indicating core research themes. (B) Network visualization of keyword co-occurrence. Each node represents a keyword, with node size proportional to its occurrence frequency. Different colors denote distinct keyword clusters, reflecting major research directions and thematic structures within the field.

Table 4. Top 20 keywords related to this research field. Rank Keyword Counts Rank Keyword Counts 1 MM 856 11 CRS 164 2 CAR-T 668 12 expression 153 3 immunotherapy 522 13 management 145 4 CAR 281 14 lymphoma 143 5 open-label 234 15 T-cells 133 6 BCMA 225 16 cancer 130 7 dexamethasone 185 17 BMT 129 8 efficacy 179 18 lenalidomide 126 9 maturation antigen 174 19 bortezomib 121 10 bispecific antibody 169 20 adoptive cell therapy 115       20 daratumumab 115 MM: multiple myeloma. BCMA: B-cell maturation antigen. CRS: cytokine release syndrome. BMT: bone marrow transplantation.

Top 20 keywords related to this research field.

MM: multiple myeloma.

BCMA: B-cell maturation antigen.

CRS: cytokine release syndrome.

BMT: bone marrow transplantation.

Following the cluster analysis of keywords, four principal clusters were identified, as depicted in Figure 5(B) . The core keyword for Cluster 1 (red) is “MM,” while “CAR-T” serves as the key term for Cluster 2 (green). Cluster 3 (blue) is characterized by the keyword “immunotherapy,” and “BCMA” is the core keyword for Cluster 4 (yellow). Furthermore, Figure 6 utilizes the period from 2013 to 2025 as a temporal framework to visually illustrate the distribution, frequency, and co-occurrence dynamics of keywords within the domain of the field, thereby providing a clear outline of the research evolution in this field (further details will be elaborated upon).

The timeline of keywords in the field of CAR-T cell therapy for MM.

Overall, the chronological distribution of keywords distinctly illustrates the developmental trajectory of this field, transitioning from foundational technological exploration to clinical application, and subsequently to detailed, in-depth research. The horizontal axis represents publication years, with node colors indicating temporal progression from 2013 (purple) to 2025 (red). Node size corresponds to keyword frequency, and connecting lines denote co-occurrence relationships. The right panel displays 12 identified keyword clusters. Analysis parameters: g-index (k = 25), LRF = 2.5, L/N = 10, LBY = 5, e = 1.0; Network N = 535, E = 1986; Modularity Q = 0.4765; Weighted Mean Silhouette S = 0.76.

Co-cited documents and reference burst

A co-citation literature analysis elucidates the academic significance and domain impact by examining the frequency with which multiple documents are concurrently cited. This study identified ten highly co-cited papers ( Table 5 ), with the pivotal phase II study of Ide-cel (bb2121) by Munshi et al. 9 ranking first (n = 699), highlighting the substantial academic influence and high co-citation frequency of this BCMA-targeted CAR-T clinical trial within the bibliometric network. The CARTITUDE-1 study concerning Cilta-cel, reported by Berdeja et al. 10 (n = 483), and the early clinical trial study by Raje et al. 11 (n = 402) closely followed, collectively representing the most frequently co-cited clinical studies within this research domain.

Table 5. The top 10 cited documents in this research field. Rank Author Title Journal Year Co-citations Centrality 1 Munshi et al. 9 Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma N Engl J Med 2021 699 0.11 2 Berdeja et al. 10 Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study Lancet 2021 483 0.02 3 Raje et al. 11 Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma N Engl J Med 2019 402 0.04 4 Cohen et al. 12 B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma J Clin Invest 2019 271 0.02 5 Rodriguez-Otero et al. 13 Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma N Engl J Med 2023 264 0.01 6 Brudno et al. 14 T Cells Genetically Modified to Express an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma J Clin Oncol 2018 255 0.02 7 Lee et al. 15 ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells Biol Blood Marrow Transplant 2019 253 0.03 8 San-Miguel et al. 16 Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma N Engl J Med 2023 246 0.01 9 Moreau et al. 17 Teclistamab in Relapsed or Refractory Multiple Myeloma N Engl J Med 2022 227 0.03 10 Martin et al. 18 Ciltacabtagene Autoleucel, an Anti-B-cell Maturation Antigen Chimeric Antigen Receptor T-Cell Therapy, for Relapsed/Refractory Multiple Myeloma: CARTITUDE-1 2 y Follow-Up J Clin Oncol 2023 221 0

The top 10 cited documents in this research field.

Citation burst analysis serves as an effective tool for identifying documents that have received significant attention within a specific timeframe, often acting as key indicators of emerging research trends within their respective fields. This study successfully employed this analytical technique to identify relevant documents exhibiting sudden increases in citation frequency, as depicted in Figure 7 . Five documents display obvious citation burst values in the bibliometric calculation, which means these works have undergone sharp citation growth during the study period from a quantitative perspective.

Top 50 documents with the strongest citation bursts.

This visualization was generated using CiteSpace. The left panel lists the complete bibliographic information for each reference, including first author, publication year, journal abbreviation, volume, page, and Digital Object Identifier (DOI). The right panel presents four quantitative metrics for each reference: Year, the calendar year of publication; Strength, reflecting the magnitude of the citation surge; Begin, the start year of the citation burst; and End, the end year of the burst. The horizontal timeline spanning 2013 to 2025 illustrates the post-publication citation history of each reference: blue bars represent the baseline period during which the reference received citations at a standard rate following publication, whereas red bars denote the specific interval of citation burst. The length of the red bar corresponds to the burst duration, and the numerical strength value indicates the intensity of the citation surge. References with red bars extending to 2025 represent ongoing bursts, signifying that these works are currently receiving high attention and thus indicate the most recently emerging research fronts.

Discussion

General information

The analysis indicates a significant upward trend in publications from 2013 to 2025. The number of documents published has surged from the early single digits to several hundred in recent years, particularly since 2020. This trend not only underscores the rapid expansion of academic output in this domain but also illustrates the comprehensive evolution of CAR-T cell therapy in MM treatment, from initial concept validation to clinical breakthroughs. Consistent with the annual trend shown in Figure 2 , the increase in publications appears to coincide chronologically with key milestones, such as the FDA approvals of ide-cel (2021) and cilta-cel (2022).

The distribution pattern of scientific research strength identified in this study significantly reflects the developmental characteristics and competitive landscape within the field of MM treatment utilizing CAR-T cell therapy. The United States demonstrates a pronounced advantage in the volume of published research, indicative of its substantial investment in the research and development of CAR-T cell technology, clinical trial infrastructure, and translational medical resources. China closely follows, showcasing a robust trajectory of increased investment in this emerging domain and its swift ascent in research output. Notably, countries such as Russia and Saudi Arabia serve a pivotal “bridge” role within the international cooperation network, leveraging their status as high intermediary centers to facilitate the cross-border exchange of knowledge, technology, and resources. It is important to emphasize that this intermediary role reflects network connectivity and collaborative bridging function rather than direct scientific leadership, research excellence, or clinical impact.

At the institutional level ( Table 1 and Figure 3(B) ), Harvard University, Mayo Clinic, and Memorial Sloan Kettering Cancer Center are ranked among the top three, underscoring the pivotal role that leading academic centers play in driving technological innovation and clinical transformation. At the periodical level ( Table 2 and Figure 4(A) ), although 422 journals are extensively covered, the core achievements are predominantly concentrated in journals specializing in immunotherapy, hematology, and oncology, reflecting the interdisciplinary nature of the research. The author’s citation analysis elucidates the trajectory of knowledge production and dissemination within the field. Foundational contributions by highly cited scholars, including James N. Kochenderfer, Marcela V. Maus, Sundar Jagannath, and Carl H. June, have established the bedrock of domain knowledge ( Table 3 ). Meanwhile, prolific researchers continue to advance the frontiers of knowledge.

The analysis of research directions and research hotspots in this research field

The keyword cluster analysis provides an objective means of identifying the primary research directions and scope within this field. Through the clustering analysis algorithm, the keywords in this field are divided into four clusters ( Figure 5(B) ). Each cluster probably represents the main research direction related to this research field.

The keywords associated with the first cluster (red) pertain to both the established standard treatments and the evolving therapeutic approaches for MM. These keywords encompass fundamental treatment modalities, including proteasome inhibitors, immunomodulators, stem cell transplantation, and bispecific antibodies. The second cluster (green) focuses on the principal themes related to the clinical application of CAR-T cells in MM. This includes the assessment of efficacy and safety, the management of adverse reactions such as CRS and ICANS, and the investigation of biomarkers for efficacy prediction and risk stratification. The third cluster (blue) addresses the fundamental and translational research on adoptive cell therapies, such as CAR-T, in hematological malignancies. The core research directions involve elucidating the mechanisms underlying anti-tumor activity, developing strategies to overcome the TME and drug resistance, and optimizing therapeutic outcomes through combination therapies. The primary keyword of the fourth cluster (yellow) elucidates the relationship between target biology and therapeutic efficacy in CAR-T therapy. The central focus is to elucidate the mechanisms of the antigen-ligand system, particularly involving BAFF/APRIL/TACI with BCMA as a pivotal element, in the context of disease diagnosis and treatment response.

The co-citation analysis of scholarly documents serves to identify the research focus within a specific academic domain by evaluating the interrelationships among multiple documents that are concurrently cited in subsequent studies. To explore the research hotspots within the field, this study conducted a co-citation analysis of the relevant literature, identifying the ten most frequently co-cited documents ( Table 5 ). 9–18 Following a thorough analysis of these documents, it has been determined that the primary research focal points in this field are concentrated on the following four aspects:

a) Investigations into the efficacy and safety of CAR-T cell therapies targeting BCMA, such as ide-cel and cilta-cel, in the treatment of R/R MM. 9–12 , 14 , 18

Bibliometric co-citation analysis ( Table 5 ) identifies the pivotal phase II studies of ide-cel (Munshi et al., rank 1) and cilta-cel (Berdeja et al., rank 2) as the most frequently co-cited clinical investigations. Their high centrality and co-citation counts quantitatively confirm that the efficacy and safety validation of anti-BCMA CAR-T products constitute the research hotspots of this research field. The KarMMa trial has established the efficacy of ide-cel in patients who have undergone multiple lines of therapy (median of six lines), demonstrating an overall response rate (ORR) of 73% and a median progression-free survival (PFS) of 8.8 months. 9 Notably, the subsequent CARTITUDE-1 study highlights the remarkable performance of cilta-cel, which incorporates a dual epitope binding domain design. This design not only enhances binding affinity to BCMA but also elevates the ORR to 97%, with 67% of patients achieving stringent complete remission (sCR). 10

b) Contrasting the effectiveness of BCMA-CAR-T cell therapy with traditional standard treatment regimens in treating R/R MM. 13 , 16

The prominent co-citation frequency and strategic positioning of the KarMMa-3 (Rodriguez-Otero et al., 13 rank 5) and CARTITUDE-4 (San-Miguel et al., 16 rank 8) trials within the bibliometric network highlight a significant paradigm shift documented in the literature. Quantitatively, these frequently co-cited comparative effectiveness studies illustrate the field’s evolving focus: transitioning CAR-T cell therapy from a ‘last-line rescue’ intervention to integration into earlier lines of treatment. Importantly, the bibliometric data indicate that comparative trials against standard-of-care regimens have formed a distinct research cluster, thereby affirming the translational maturity of this therapeutic approach.

c) To establish a consensus on the standardized grading of CAR-T cell therapy-related toxicities (CRS, ICANS), clarify the mechanism of occurrence, and optimize the management strategy. 9–11 , 15

With the extensive application of CAR-T cells in hematological malignancies, associated toxicities, particularly CRS and ICANS, have emerged as significant concerns limiting its clinical safety. 19 , 20 This study shows that the American Society for Transplantation and Cell Therapy (ASTCT) consensus grading standard for CRS and ICANS 15 has emerged as a pivotal document, extensively cited (citation counts n = 253; Table 5 ). A notable increase in citations is observed from 2023 to 2025 ( Figure 7 ), underscoring the standard’s critical role in establishing a globally unified framework for assessing adverse events. The co-occurrence of “CRS,” “management,” and “ICANS” within the same keyword cluster (Cluster 2, green; Figure 5(B) ) quantitatively affirms that the optimization of safety is inherently linked to the evaluation of clinical efficacy within this research domain. The establishment of the classification system by the ASTCT has introduced a standardized terminology for global research, significantly facilitating the comparison of data across studies.

d) Application of bispecific antibodies (e.g., Teclistamab) in the treatment of MM and exploration of complementary strategies with CAR-T cell therapy. 17

Bispecific antibodies (BsAbs) and CAR-T cell therapy have emerged as two key pillars of immunotherapy for R/R MM. Teclistamab, the first approved BCMA×CD3 bispecific antibody, has demonstrated remarkable efficacy in heavily pretreated patients. 21 , 22 Moreover, compared with BCMA-targeted CAR-T cell therapy, BsAbs offer the advantage of being an “off-the-shelf” therapy, thereby providing better accessibility. Teclistamab exerts its antitumor effects by recruiting and activating T cells to eliminate BCMA-expressing multiple myeloma cells, a mechanism that has been validated in both preclinical and clinical studies. 23 In summary, BsAbs possess extensive potential applications in the management of R/R MM and may produce synergistic effects when combined with CAR-T cell therapy. 24 , 25 Nevertheless, the extent to which these preclinical or early-phase findings translate into clinically significant enhancements in efficacy, safety, or optimal sequencing necessitates further dedicated prospective research.

The evolution of research hotspots and the exploration of emerging topics

Between 2013 and 2025, the research focus on the field has undergone significant evolution, encapsulating the transition from foundational exploration to advanced clinical research in this domain ( Figure 6 ). The period from 2013 to 2016 represents the initial exploration phase, during which research primarily concentrated on the basic classification of hematological malignancies and the development of adoptive cell therapy technologies. In 2015, “CAR-T” emerged as the most frequently cited keyword of the year, signifying the establishment of this technology as a central research focus in the field. Concurrently, preliminary attention was directed toward the safety and anti-tumor efficacy of the treatment, thereby laying the groundwork for future investigations.

Between 2017 and 2021, the field experienced a significant phase of clinical expansion and product development, with research trends characterized by three main features: integration, precision, and commercialization. The integration strategy involving immunomodulatory drugs (such as lenalidomide and pomalidomide), CD38 monoclonal antibodies (such as daratumumab), and CAR-T cell therapies emerged as the predominant approach. The standardized assessment of minimal residual disease (MRD) has facilitated advancements in evaluating therapeutic efficacy. Furthermore, the concentrated dissemination of clinical trial data for commercial products like ide-cel and cilta-cel from 2019 to 2021 signifies a transition from academic research to industrial application. Concurrently, BsAbs have gained prominence, establishing a competitive yet complementary dynamic with CAR-T cell therapies.

Between 2022 and 2025, the field experienced a significant phase of advancement in addressing drug resistance and expanding real-world applications. Following the FDA’s approval of the first BCMA-CAR-T product, research priorities transitioned toward the management of long-term survival. This included a focus on infection complications, immune reconstitution kinetics, and the mechanisms of T cell depletion, which emerged as distinct areas of interest. The development of novel targets, such as GPRC5D, became imperative to counteract BCMA antigen escape. Additionally, the approval of bispecific antibodies like Teclistamab and Talquetamab facilitated the integration of the “immunotherapy puzzle.” Post-2023, there was a notable increase in the prominence of terms such as “real-world,” “quality of life,” and “guidelines,” indicating a shift toward standardization within the field. This shift reflects a transition in focus from “maximizing curative effect” to “minimizing toxicity” while balancing cost and benefit.

Citation burst analysis ( Figure 7 ) identified five documents with ongoing bursts. Upon examining these five studies, it was observed that three align with previously identified research hotspots, 15 , 17 , 18 indicating that the research directions represented by these studies are both research hotspots and emerging topics. The remaining two emerging research topics are as follows:

a) Application and efficacy evaluation of CAR-T cell therapy targeting GPRC5D in BCMA targeted therapy for patients with MM recurrence. 26

The investigation into the application and therapeutic efficacy of CAR-T cell therapy targeting GPRC5D in patients experiencing relapse following BCMA-targeted therapy has emerged as a significant area of research within the treatment of MM. Despite the notable success of BCMA-targeted CAR-T cell therapy in treating R/R MM, the recurrence rate remains substantial, primarily due to antigen escape. 27 Consequently, the identification and exploration of novel targets, such as GPRC5D, have become focal points of ongoing research. The citation burst analysis depicted in Figure 7 highlights the study on GPRC5D-targeted CAR-T therapy by Mailankody et al. 26 as a document exhibiting significant ongoing citation bursts. This analysis provides objective bibliometric evidence, indicating that GPRC5D has become an important target to deal with the escape of BCMA antigen. These findings indicate that GPRC5D may be a viable and safe target, particularly for patients who experience relapse following BCMA-targeted therapy. 28 , 29

b) Feasibility, safety, and preliminary efficacy evaluation of allogeneic BCMA-CAR-T cells in R/R MM. 30

The UNIVERSAL trial interim results (Mailankody et al. 30 ) register a prominent citation burst ( Figure 7 ), reflecting a marked rise in the academic community’s interest in “off-the-shelf” allogeneic BCMA-CAR-T products in recent years. The investigation into the feasibility, safety, and preliminary efficacy of allogeneic BCMA-CAR-T cells for the treatment of R/R MM represents a significant research trajectory within the domain of tumor immunotherapy. In comparison to autologous CAR-T cell therapy, allogeneic CAR-T cell therapy offers advantages such as a reduced production timeline and lower manufacturing costs. Furthermore, through the application of gene editing technologies, allogeneic CAR-T cells can mitigate the risk of graft-versus-host disease (GvHD) while demonstrating promising anti-tumor activity in preclinical studies. 31 Notably, CAR-T cells derived from healthy donors exhibit enhanced cytotoxicity and greater proliferative capacity both in vitro and in vivo, thereby providing a theoretical foundation for their clinical application. 32

Although the present bibliometric analysis identified rapidly expanding research interest in CAR-T cell therapy for MM, particularly in areas related to BCMA-targeted therapies, relapse mechanisms, antigen escape, dual-targeting strategies, and combination approaches, these findings should be interpreted with caution. It is critical to emphasize that bibliometric data reflect publication volume, citation patterns, and thematic evolution within the academic literature; they do not, by themselves, establish comparative clinical superiority, optimal treatment sequencing, formal therapeutic indications, or clinical practice recommendations. Decisions regarding treatment selection, sequencing, and future clinical application require validation through well-designed prospective clinical trials, real-world evidence, long-term follow-up data, and guideline-level consensus. In this context, our findings are intended to provide a macroscopic overview of the evolving research landscape and to help identify areas requiring further clinical investigation, rather than to recommend specific therapeutic strategies.

Limitations

This study has several limitations. Firstly, the literature retrieval process was confined to the WoSCC database. Although this database contains most of the literature in this field, it still misses a few related publications. Secondly, the search strategy was restricted to English-language literature, potentially introducing language bias and failing to adequately represent the research contributions from non-English-speaking countries. Thirdly, bibliometric analysis primarily focuses on quantitative indices, which, while useful for illustrating research trends and the overall knowledge structure, do not allow for a comprehensive evaluation of the methodological quality, innovation, and clinical applicability of individual studies. Future research should consider integrating systematic reviews and Meta-analyses to provide a more thorough synthesis of evidence and quality assessment of the key areas identified in this study.

Conclusion

This bibliometric analysis (2013–2025) quantitatively mapped the global research landscape of CAR-T cell therapy for MM. The United States, Harvard University, Frontiers in Immunology , and Hermann Einsele were the leading contributors by country, institution, journal, and author, respectively. Research hotspots center on BCMA-targeted CAR-T efficacy and safety, comparative effectiveness against standard regimens, toxicity management, and combinatorial strategies with bispecific antibodies. Citation burst analysis further indicates that GPRC5D-targeted CAR-T cell therapy, allogeneic “off-the-shelf” products, toxicity optimization, and earlier-line integration represent active research directions that require further clinical validation through prospective trials and real-world evidence.

Supplementary Material

Supplementary materials.docx

Acknowledgments

T.Z.: Writing-Original draft, data curation, investigation, and visualization. S.W.: Writing-Original draft, investigation, and visualization. X.L.: Investigation and visualization. X.L.: Writing – review & editing, Methodology, Supervision. Y.W.: Writing – review & editing, Conceptualization, Methodology, Supervision.

Biography

Yamei Wu , PhD, is an associate chief physician. She has a proficient command of advanced techniques such as hematopoietic stem cell transplantation and offers unique insights into the treatment of refractory and relapsed hematological malignancies. She has long been engaged in basic and clinical research, focusing on the mechanisms of drug resistance in hematological tumors and strategies to overcome them, as well as research related to CAR-T cells.

Funding Statement

The author(s) reported there is no funding associated with the work featured in this article.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.

Supplementary Information

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21645515.2026.2711554

References

Associated Data

Supplementary Materials

Supplementary materials.docx

Data Availability Statement

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.