Visualizing immunotherapy for multiple myeloma worldwide from 2013 to 2023: A bibliometric analysis.

Introduction

Multiple myeloma (MM) is a heterogeneous and incurable tumor characterized by monoclonal plasma cells accumulating in the bone marrow and producing M protein. The main clinical manifestations include bone destruction, renal injury, anemia and hypercalcemia. 1 , 2 It is the second most common hematological malignancy worldwide. Currently, proteasome inhibitors, immunomodulators, and steroids are the first-line treatments for MM, significantly improving patient prognosis. 3 , 4 However, MM remains incurable, highlighting the urgent need for new treatment strategies.

MM is characterized by progressive immune dysfunction, 5 , 6 leading to a significant focus on immunotherapy in MM research over the past two decades. The first immunotherapy was hematopoietic stem cell transplantation. This was followed by immunomodulators (such as Thalidomide, Lenalidomide) and monoclonal antibodies (such as Daratumumab). More recent advancements in immunotherapy for MM include chimeric antigen receptor T cells (CAR-T), bispecific antibodies, antibody-drug conjugates, and checkpoint inhibitors. 7 Patients have achieved deeper responses and longer survival with the use of immunotherapy. Therefore, a systematic analysis and discussion of the literature and research trends in immunotherapy for MM is essential.

Bibliometrics is a method used for analyzing the characteristics and development trends of literature. 8 A comprehensive analysis of various indicators, including the number of documents, countries, institutions, authors, citations, and keywords, enables researchers to efficiently process extensive literature. This analysis facilitates the visualization of relationships such as citation patterns, collaborations, and co-occurrences within the literature. Consequently, it aids in understanding the current development status and trends within specific fields, identifying research hotspots, enhancing the efficiency of scientific inquiry, and supporting academic research and discipline development. 9 , 10 As a quantitative analysis method, bibliometrics provides an intuitive and objective assessment of past academic research activities and achievements, thereby mitigating the bias in paper evaluations that may arise from human factors. This method has been extensively applied across various fields, including oncology, organ transplantation, vaccines, and immunotherapy. However, there is a lack of literature on bibliometric analysis of immunotherapy for MM.

In this study, we systematically searched relevant literature on immunotherapy for MM from 2013 to 2023 and applied bibliometric methods to analyze the research status and potential future trends in this area. Through bibliometric analysis, researchers can simultaneously assess the global research landscape of MM immunotherapy. This understanding aids in the formulation of clinical treatment plans and provides insights into emerging trends in MM immunotherapy, thereby establishing a foundation for the development of more innovative treatment strategies.

Materials and methods

Data sources and search strategies

The Web of Science (WoS) database is a widely used resource for bibliographic analysis of scientific literature. In this study, all publications related to immunotherapy for MM f from January 1, 2013, to December 31, 2023, were searched on January 17, 2024, within the WoS core collection database. The search formula was: TS = (“multiple myeloma”) AND TS = (“immunotherapy” OR “immune therapy” OR “immunization therapy” OR “immunotherapies” OR “immunity treatment” OR “immunotherapeutic”). For articles to be included in the study, the title, key words and abstract of the article should be related to the immunotherapy of MM.

Screening process

The study focused on immunotherapy for Multiple Myeloma (MM) with full text available, meeting the criteria of being published in Sciences Citation Index Expanded (SCI-E) and Social Sciences Citation Index (SSCI) of WoS. The publication types considered were limited to “article” and “review,” written in English, and falling within the time period of 1 January 2013 to 31 December 2023. Jinqiao Li and Wenyi Hou, as authors, independently assessed all publications full texts. Any discrepancies were resolved through negotiation between the two authors. The data was exported in plain text format.

Visualization and statistical analysis

Bibliometrics is utilized for analyzing the cutting-edge knowledge and research trends in a specific research field. The results of the analysis were visualized using the VOS viewer (1.6.19) and Citespace (6.2.R6). CiteSpace aids researchers in tracking the advancements and trends within the research domain, enhancing their comprehension of the field. 11 VOS viewer offers a straightforward method for analyzing and showcasing extensive literature data. 12 Furthermore, Microsoft Excel 365 was employed for data analysis.

The results are depicted in figures or tables, where nodes within the figures represent various elements such as keywords, institutions, countries, authors, and journals. The size of the nodes indicates the frequency of referencing or appearance, while the links between nodes depict relationships like cooperation, co-occurrence, and co-citation. Nodes and links of different colors symbolize different years, and the red dot represents the burst. The centrality index is utilized to assess the significance of each node, nodes with a centrality greater than 0.1 are highlighted by a purple outer ring. In a network diagram, a node with high centrality indicates that it is a connection hub between two sets of nodes, or is highly connected to other nodes. Furthermore, The analysis also included the 2022 Journal Citation Report (JCR) and the Impact Factor (IF).

Results

Trend of annual publication

Analysis revealed that a total of 1018 articles pertaining to MM immunotherapy were published on WoS between January 1, 2013 and December 31, 2023, comprising 570 articles (56.0%) and 448 reviews (44.0%). Figure 1 illustrates the publication trend on immunotherapy for MM over the specified period. Notably, as a classic area of research in MM, the field has experienced a steady growth in publications over the last decade, with a relatively stagnant trend observed prior to 2016. Subsequently, from 2016 to 2019, there was a slight increase in publications, followed by a rapid rise post-2019. In 2021, the number of publications on MM immunotherapy reached its peak in the past 10 years. Figure 1. Annual trends of MM immunotherapy related-articles from 2013 to 2023.

Countries/Regions analysis

The United States leads in the number of publications with 432 (42.44%), followed by China with 177 (17.39%), Italy and Germany with 108 each (10.61%) ( Figure 2a ). These countries have been actively researching MM immunotherapy from 2013 to 2023 ( Figure 2b ) and have shown close collaboration (Supplementary Figure S1A). Among the top ten countries, the United States stands out with 17,545 citations, far exceeding others ( Table 1 ). The United Kingdom has the highest citation/publication ratio at 57.24, showcasing the high quality of British publications. Japan has the lowest number of citations and citation/publication ratio. Russia exhibits the fastest growth in publications and the strongest citation burst intensity (Supplementary Figure S1B). The annual publication trends of the top ten countries are also visualized ( Figure 3 ). Figure 2a. Top 10 countries that published MM immunotherapy related-articles from 2013 to 2023. Figure 2b. Co-operation among countries that published MM immunotherapy related-articles. Figure 3. Annual trends of the top 10 countries that published MM immunotherapy related-articles from 2013 to 2023. Table 1. The top 10 most published countries/regions related to immunotherapy for MM from 2013–2023. Rank Country/Region Article counts Citation Citation per articles 1 USA 432 17545 40.61 2 CHINA 177 3681 20.80 3 ITALY 108 3639 33.69 4 GERMANY 108 3448 31.93 5 SPAIN 65 2606 40.09 6 NETHERLANDS 64 3278 51.22 7 FRANCE 56 2289 40.88 8 ENGLAND 46 2633 57.24 9 JAPAN 36 592 16.44 10 AUSTRALIA 32 1052 32.88

Institution analysis

Harvard University has the highest number of publications, with 85 publications, followed by Harvard Medical School (62 publications) and Dana-Farber Cancer Institute (60 publications) ( Figure 4a ). Over the past decade, institutions have shown dedication to the study of MM immunotherapy ( Figure 4b ). Additionally, a network diagram of institutional collaboration reveals that institutions with the most publications cooperate closely (Supplementary Figure S2A). Among the top 10 institutions with the most publications, seven are based in the United States ( Table 2 ), highlighting the active involvement of American research institutions in MM immunotherapy. The Dana-Farber Cancer Institute received the highest number of citations, with 2845 citations, while the Mayo Clinic had the highest citation/publication ratio (82.32). Among the 25 institutions with the strongest citation burst, there are still 6 institutions with explosive growth in the number of publications so far (Supplementary Figure S2B.), indicating that immunotherapy for MM is not only a classic topic, but also still has great research value. Figure 4a. Top 10 institution that published MM immunotherapy related-articles from 2013 to 2023. Figure 4b. Co-operation among institutions that published MM immunotherapy related-articles. Table 2. The top 10 most published institutions related to immunotherapy for MM from 2013–2023. Rank Institutions Country Article counts Citation Citation per articles 1 Harvard University USA 85 884 10.40 2 Harvard Medical School USA 62 2003 32.31 3 Dana-Farber Cancer Institute USA 60 2845 47.42 4 Memorial Sloan Kettering Cancer Center USA 45 2464 54.76 5 University of Texas System USA 32 1271 39.72 6 Mayo Clinic USA 31 2552 82.32 7 University of Wurzburg Germany 31 417 13.45 8 University of Pennsylvania USA 31 2060 66.45 9 Vrije Universiteit Amsterdam Netherlands 31 812 26.19 10 Institut National de la Sante et de la Recherche Medicale (Inserm) France 29 278 9.59

Research fields analysis

Oncology is the most published research field, with 468 publications, followed by hematology (296 publications) and immunology (225 publications) ( Figure 5 ). The research field encompasses various disciplines such as cell biology, pathology, pharmacology and pharmacy, biochemistry and molecular biology, chemistry, microbiology and others, highlighting the multidimensional nature of immunotherapy research for MM. Figure 5. Research areas of immunotherapy for MM-related studies.

Authors analysis

The authors with the highest number of citations were Lonial Sagar, Palumbo Antonio, and Kumar Shaji K, with 340, 331, and 282 citations respectively. In terms of productivity, Anderson Kenneth C had the most publications with 27, followed by Einsele Hermann with 25, and van de Donk Niels W C J with 22 publications ( Table 3 ). Most of these prolific authors collaborated closely with a consistent team ( Figure 6 ). Anderson Kenneth C and their team have made significant contributions to the field, particularly in the realm of novel targets and immune microenvironments for MM immunotherapy. Figure 6. Cooperative network of MM immunotherapy related-articles between authors. Table 3. The top 10 most published authors and cited authors related to immunotherapy for MM from 2013–2023. Rank Cited authors Frequency Author Article counts 1 Lonial, Sagar 340 Anderson, Kenneth C 27 2 Palumbo, Antonio 331 Einsele, Hermann 25 3 Kumar, Shaji K 282 van de Donk, Niels W C J 22 4 Tai, Yu-Tzu 268 Mutis, Tuna 17 5 Dimopoulos, Meletios A 263 Tai, Yu-Tzu 16 6 Moreau, Philippe 254 Avigan, David 14 7 Raje, Noopur 222 Rasche, Leo 13 8 Anonymous 222 Hudecek, Michael 11 9 Rajkumar, S Vincent 220 Danhof, Sophia 11 10 Mateos, Maria-Victoria 219 Rosenblatt, Jacalyn 11

Journals analysis

In the field of immunotherapy for MM, the most frequently published journals are CANCERS and FRONTIERS IN IMMUNOLOGY, with 60 publications respectively, followed by BLOOD (35 publications) and FRONTIERS IN ONCOLOGY (30 publications) (Supplementary Figure S3A). The most cited journals include BLOOD (991 times), LEUKEMIA (823 times) and CLINICAL CANCER RESEARCH (773 times) (Supplementary Figure S3B).

Among the top 10 journals, BLOOD had the highest Impact Factor (IF) in 2022 (20.3), followed by CLINICAL CANCER RESEARCH (11.5) and LEUKEMIA (11.4). Eight journals were classified as Q1, while one journal each was classified as Q2 and Q3. ( Table 4 ). Table 4. The top 10 most published journals related to immunotherapy for MM from 2013–2023. Rank Journals Article counts Citation Citation per articles JCR partition IF (2022) 1 CANCERS 60 239 3.98 Q1 6.2 2 FRONTIERS IN IMMUNOLOGY 60 462 7.70 Q1 7.3 3 BLOOD 35 991 28.31 Q1 20.3 4 FRONTIERS IN ONCOLOGY 30 198 6.60 Q2 4.7 5 JOURNAL FOR IMMUNOTHERAPY OF CANCER 28 187 6.68 Q1 10.9 6 BRITISH JOURNAL OF HAEMATOLOGY 24 653 27.21 Q1 6.5 7 CLINICAL CANCER RESEARCH 22 773 35.14 Q1 11.5 8 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 22 159 7.23 Q1 5.6 9 LEUKEMIA 22 823 37.41 Q1 11.4 10 CLINICAL LYMPHOMA MYELOMA&LEUKEMIA 21 231 11.00 Q3 2.7

Additionally, a double-map overlay of journals was created to illustrate the citation relationships. The citing journals are displayed on the left, while the cited journals are shown on the right ( Figure 7 ). The color lines represent the reference paths, the labels indicate the subject areas represented by the journals, and colors are used to represent the two main citation paths. The analysis revealed that journals publishing MM immunotherapy articles were predominantly focused on Molecular/Biology/Immunology and Medicine/Medical/Clinical, whereas journals influencing MM immunotherapy development were primarily concentrated in Molecular/Biology/Genetics and Health/Nursing/Medicine. Two main citation relationships were identified: the orange citation path indicates that the research of Molecular/Biology/Genetics is frequently cited by Molecular/Biology/Immunology journals, and the green citation path indicates that the research of Molecular/Biology/Genetics is frequently cited by Medicine/Medical/Clinical journals. Figure 7. The dual-map overlay of journals on MM immunotherapy-related studies.

Co-citation analysis

The co-cited reference was basically divided into 8 clusters (Supplementary Figure S4), including car t cell, checkpoint inhibition, monoclonal antibody therapy, bispecific antibodies, hematologic malignancies, etc. Cluster 0 is the cluster with the most keywords, indicating that it has been the most extensively studied in immunotherapy for MM.

The most frequently co-cited literature was Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma by Lonial S et al. in 2015 (188 times), followed by Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma by Raje N et al. in 2019 (183 times) and Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma by Palumbo A et al. in 2016 (150 times) (Table S1). Above three articles were published in NEW ENGL J MED. Of the top 10 co-cited articles, 60% were published in NEW ENGL J MED journal, which had an IF of 158.5 in 2022. In addition, the top co-cited literature tended to be more collaborative.

A timeline diagram of the co-cited references showed that different research hotspots emerged over time ( Figure 8 ), with older research focusing on #6 cancer-testis antigen and newer relatively new research on #3 bispecific antibodies which still being studied by many researchers. The common research hotspots included the search for drug targets, the clinical application of immune checkpoint inhibitors and monoclonal antibodies, such as #1 checkpoint inhibition and #2 monoclonal antibody therapy. Figure 8. Timeline view of co-cited references related to immunotherapy for MM.

Keywords analysis

After consolidating keywords with similar meanings, a keyword co-occurrence network was created ( Figure 9 ). The most frequently used keywords were Multiple myeloma (611 times), followed by expression (175 times) and immunotherapy (172 times) ( Table 5 ). Figure 9. Co-operation among keywords of MM immunotherapy related-article. Table 5. The top 10 keywords of immunotherapy for mm-related studies. Rank Frequency Keywords 1 611 Multiple myeloma 2 175 Expression 3 172 Immunotherapy 4 158 Therapy 5 153 Natural killer cell 6 143 Bone marrow 7 142 Open label 8 139 Monoclonal antibody 9 138 T cells 10 126 Lenalidomide

These keywords were categorized into 17 clusters, this article lists the top 10 clusters (Supplementary Figure S5), which mainly focus on target, drug resistance, daratumumab, autologous transplantation, adoptive cell therapy. It can be seen that in the immunotherapy of MM, targeted therapy, autologous transplantation and adoptive cell therapy are the most concerned treatment methods.

Burst keywords indicate that a keyword has been frequently cited over a period of time. Identifying burst keywords can help pinpoint research frontiers. The top 15 burst keywords have been enumerated ( Figure 10 ). Notably, the most recent burst keywords include bispecific antibody and preclinical activity, indicating that there are still many ongoing preclinical investigations in MM immunotherapy and the potential application of novel immunotherapies in clinical settings in the future. Figure 10. Top 15 keywords with the strongest citation bursts.

Discussion

Multiple myeloma (MM) is a malignant, proliferative disease of the plasma cells, with approximately 588,000 people worldwide being diagnosed with the disease each year. It ranks as the second most common hematological malignancy in adults. 2 , 13 Research indicates that over the past 20 years, the prognosis for patients with MM has markedly improved. Nowadays, the median overall survival (OS) for patients classified as standard-risk can extend to 7 to 10 years, whereas high-risk patients can expect a median OS of approximately 5 years. 14–17 This study delves into the research progress of immunotherapy for MM from 2013 to 2023, offering new insights into the future direction of research and development in this area.

Bibliometric methods were used to analyze the growth trend of MM immunotherapy related research in the past ten years. According to the annual number of publications, the growth of research related to immunotherapy for MM can be divided into three stages. Before 2016, the field was in a slow growth stage, with an annual volume of approximately 40 articles. From 2016 to 2019, the annual number of publications increased to around 80, effectively doubling from the previous stage. After 2019, the number of papers published each year exceeded 130, marking the onset of a rapid development phase. We speculate that this may be due to the fact that Daratumumab and Elotuzumab were approved for the treatment of MM in 2015; 18–20 Belantamab mafodotin, the world’s first approved B cell maturation antigen (BCMA) targeted therapy in 2020, also has propelled the field of MM immunotherapy to a new level. 21

Recent years have seen a surge in interest among researchers regarding the relationship between immunotherapy and MM, the US author ANDERSON KC ranked first in terms of the number of published papers. In the analysis of the number of national publications, the United States is far ahead in this field. Harvard University and its affiliated medical institutions stand out as the most prolific contributors to publications in this research domain. The findings confirm the significant contribution and leading position of the United States in the research of MM immunotherapy. This prominence may be attributed to the United States being a developed country, characterized by superior economic conditions, substantial medical investments, and more accessible clinical opportunities following drug approval. Developing countries could engage in extensive international research collaborations with developed nations to enhance their publication output and scientific research progress, thereby improving their clinical diagnostic and treatment capabilities.

The substantial number of published papers and the high frequency of citations offer valuable insights for researchers seeking to identify high-quality journals. Among the top ten journals, eight are classified as JCR Q1. The journal with the highest citation frequency was BLOOD, followed closely by LEUKEMIA, both of which are leading journals in the field of hematology. This not only underscores the authority of the aforementioned journals in the field of MM immunotherapy but also highlights the significant interest of leading scholars in this research area. Monitoring these journals will enable researchers to stay updated on new advancements and inform clinical treatment strategies.

The number of citations serves as one indicator for measuring the academic influence of a paper. Highly cited literature can reflect prevailing trends and foundational research within a specific field. This analysis focuses on the top ten most cited references and authors who have concentrated on the application of Daratumumab in MM, the use of BCMA CAR-T therapy, and the treatment of relapsed/refractory MM(RRMM).

In 2015, the study by Lokhorst HM et al. demonstrated that daratumumab, a humanized antibody targeting CD38, exhibits single-agent anti-tumor activity in patients with RRMM. Among patients who achieved complete remission and very good partial remission as a result of daratumumab monotherapy, 65% remained progression-free at 12 months. 20 In 2016, a study conducted by Palumbo A team and Dimopoulos MA team demonstrated that in patients with RRMM, the addition of daratumumab to treatment significantly prolongs progression-free survival compared to traditional therapies. Specifically, the risk of disease progression or death in patients receiving daratumumab, bortezomib, and dexamethasone was found to be 61.4% lower than in those treated with bortezomib and dexamethasone alone. 22 Furthermore, the incorporation of daratumumab into the regimen of lenalidomide and dexamethasone reduced the risk of disease progression or death by 63%. 23

In 2013, Carpenter RO et al. demonstrated that BCMA was exclusively expressed in MM cell lines, while not being expressed by hematopoietic stem cells or normal non-hematopoietic cells, as confirmed through immunohistochemistry, flow cytometry, and quantitative PCR. Additionally, they designed and tested emerging anti-BCMA CARs. 24 It is proposed that BCMA is a suitable target for CAR T cells, and adoptive transfer of anti-BCMA-CAR-expressing T cells is a promising new strategy for treating MM. In 2016, Ali SA and his team conducted the first human clinical trial of BCMA CAR-T cells, demonstrating that BCMA CAR-T therapy exhibits significant efficacy in patients with MM who are resistant to standard treatments. Furthermore, CAR-T cells targeting BCMA hold substantial promise as a novel and effective treatment option for MM. 25 In 2019, the Cohen AD team conducted a Phase I study on the transduction of autologous T cells using a human BCMA-specific CAR lentivirus in patients with RRMM. Among the 25 subjects, the median number of prior treatments before enrollment was seven lines. Notably, 96% of the participants were dually resistant to proteasome inhibitors (PIs) and immunomodulatory drugs (IMIDs), while 72% exhibited resistance to daratumumab. Additionally, 44% were resistant to bortezomib, lenalidomide, carfilzomib, pomalidomide, and daratumumab. Furthermore, 96% of the subjects had at least one high-risk cytogenetic abnormality, with 68% demonstrating either a 17p deletion or TP53 mutation. The median proportion of myeloma cells in bone marrow biopsies was 65%, and 28% of the subjects presented with extramedullary lesions. 26

The emergence of immunotherapy has led to significant advancements in the treatment of RRMM. A study conducted by Sagar Lonial, M.D., and his team in 2015 demonstrated that in patients with recurrent or refractory MM, the combination of the SLAM7 monoclonal antibody Elotuzumab with lenalidomide and dexamethasone resulted in improved outcomes. Specifically, compared to the administration of lenalidomide and dexamethasone alone, the median progression-free survival was extended by 4.5 months ( p < .001), and the overall response rate increased by 13% ( p < .001). 19 In the treatment of BCMA CAR therapy, a study involving 16 patients with refractory MM (median number of treatments: 9.5) demonstrated a median event-free survival of 7.1 months. However, 38% of patients experienced grade 3 or higher cytokine release syndrome. This study was modified to only treat myeloma patients with less than 30% of bone marrow plasma cells. 27 Two clinical trials investigating idecabtagene vicleucel, a B cell mature antigen-directed chimeric antigen receptor T cell therapy, have demonstrated its clinical efficacy in patients with RRMM. Among the 140 patients who had undergone at least three treatment regimens, 128 received ide-cel. The median duration of remission was 10.7 months, while the progression-free survival was recorded at 8.8 months. Notably, 26% of patients achieved minimal residual disease (MRD)-negative status. 28 , 29 Due to the incurable nature of MM, the treatment of RRMM will always be a research hotspot. Keywords can reflect the core content of the research. In this study, the top three keywords were ‘Multiple myeloma,’ ‘Expression’ and ‘Immunotherapy,’ of which ‘Expression’ appeared 175 times, indicating that researchers have more research on cell surface molecular phenotypes, which may provide help for further search for drug treatment targets. Keyword clustering analysis takes the words with significant characteristics in this field as the clustering object, and carries out aggregation and classification to present the focus of research in this field. In this study, after clustering the keywords, ‘drug resistance’ is the second-ranked cluster, reflecting that in the context of the rapid development of MM immunotherapy, the exploration of drug resistance is also a major concern of researchers. Current studies indicate that the resistance mechanisms of immunomodulators (thalidomide, lenalidomide, and pomalidomide) can be categorized into several key areas. First, mutations in the pons and pons pathways, specifically in the IFKF1 and KPNA2 genes, along with mutations in the RAS/RAF signaling pathway (notably KRAS G12D and BRAF V600E), lead to reduced expression of target genes. Additionally, mutations in the pons and pons pathway genes result in alterations in genetic and genomic profiles. Second, a stem cell-like phenotype is observed, characterized by increased levels of multidrug transporters (ABCG2/BCRP) and elevated ALDH1A1 enzyme activity. This is accompanied by the activation of the Hedgehog, WNT, and Notch pathways, as well as the upregulation of the BTK receptor and RARa2, which contribute to a sustained increase in cancer stem cells. Lastly, an increase in cell adhesion molecules, particularly CD44, influences the Wnt/β-catenin signaling pathway, thereby altering the bone marrow microenvironment. The resistance mechanisms of monoclonal antibodies can be categorized into four main types: 1. A decrease in the expression of CD38 and SLAM7, which results in antigen escape; 2. An increase in the expression of CD46, CD56, and CD59 due to complement-dependent cytotoxicity induced by blocking antibodies, leading to complement resistance; 3. The competition between extracellular soluble forms of CD38 and SLAM7, which alters the bone marrow microenvironment; and 4. The presence of anti-idiotypic antibodies that neutralize the activity of therapeutic monoclonal antibodies. 30 The resistance to CAR T cell therapy may be related to antigen escape, T cell dysfunction or depletion, and immunosuppressive bone marrow microenvironment. 31–36 Burst analysis can identify keywords that change significantly over time, and researchers can use emergent keywords to explore research hotspots. In the field of MM immunotherapy, the latest development trends are bispecific antibody and preclinical activity. Bispecific antibody is defined as a pharmaceutical compound constituted of two monoclonal antibodies. It comprises two binding domains, enabling it to bind simultaneously to two different antigens. This unique feature provides a significant advantage over other treatment options. I In MM therapy, bispecific antibodies target specific molecules on malignant plasma cells and CD3 on T cells, activating T cells independently of the major histocompatibility complex and T cell receptor specificity. 37 , 38 This innovative approach directly activates T cells and triggers tumor cell death, offering a promising strategy for refractory MM cases. Several MM cell targets showing efficacy in prior clinical trials (such as GPRC5D, FcRH5 et.al) are now in phase I/II clinical trials. 39–43

In recent decades, tumor immunotherapy has emerged as a promising treatment for various cancers, also has been extensively utilized in the treatment of MM. Targeted therapies, such as daratumumab, are not only indicated for patients with RRMM but have also received approval for first-line treatment. This allows patients to attain early deep remission, prolong the time to recurrence, and enhance their quality of life. Looking ahead, immunotherapy is poised to become the primary treatment modality for MM, particularly in RRMM cases. This study for the first time utilized bibliometric methods to systematically analyze the existing literature on immunotherapy for MM, providing researchers and clinicians with a comprehensive and objective understanding of the development trend and research frontiers in this field to guide the selection of clinical treatment options. At the same time, this study still has some limitations. This paper only retrieves the research in the WoS database, which may result in the omission of related research from other databases. Furthermore, this paper only includes articles published in English, neglecting research published in other languages. Future studies should explore articles from diverse databases and languages to enhance our comprehensive understanding of the application of immunotherapy in MM.

Supplementary Material

Supplementary.docx

Wenyi Hou , MD. While undertaking her PhD research, she worked on acute promyelocytic leukemia with a focus on coagulation-related early death. She is currently working in the Department of Hematology of the First Affiliated Hospital of Harbin Medical University, has gained considerable experience in the diagnosis and treatment of various hematological malignant diseases, particularly multiple myeloma and other plasma cell diseases.

Disclosure statement

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

Author contributions

Jinqiao Li, Wenyi Hou: data collection and retrieval. Jinqiao Li, Wenyi Hou: figure and table preparation. Jinqiao Li: write the original manuscript. Xiaoxia Li, Yueyue Fu, Hongbin Meng and Dan Xu: supervision and conceptualization. Xiaoxia Li, Wenyi Hou: modify the manuscript. All authors reviewed the manuscript. All authors read and approved the final manuscript.

Data availability statement

Datasets used and analyzed in this article are available on request from the corresponding author.

Ethical approval

All analyzes were based on literature studies and did not require ethical approval or patient consent.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2024.2433304 .

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