With the close of 2024, we wanted to take stock of the eighth year for Blood Advances, which had another banner year. We continue to receive an impressive number of submissions, both cascaded from Blood and submitted directly to Blood Advances. In 2024, Blood Advances’ impact factor was 7.4, with the total citations for the journal increasing by an impressive 19% from the previous year. The journal now ranks among the top 12% of all hematology journals.
None of this would be possible without our incredible editorial team of associate editors: Carl Allen, Michael DeBaun, Geoffrey Hill, Claudia Lengerke, Georg Lenz, Shannon Maude, Ryan Morin, Olatoyosi Odenike, Margaret Ragni, Noopur Raje, Wendy Stock, Constantine Tam, and Alisa Wolberg, along with Rayne Rouce, our digital commissioning editor.
The clinical guidelines continue to be among our most cited articles. Developed by the guideline oversight subcommittee composed of experts supported by the American Society of Hematology (ASH), these guidelines are clearly important to our readership!
As 2024 draws to a close, we wanted to highlight the articles that have an immunotherapy/cell and gene therapy focus, appreciating this rapidly developing field with increasing T-cell therapy products available for patients with blood cancers. Moreover, with the recent US Food and Drug Administration (FDA) approvals of gene therapy products for sickle cell disease and hemophilia, the cell and gene therapy field is clearly also of increasing importance for the classical hematology field.
We have therefore selected the following articles that were published in 2023 and 2024 to highlight:
The rules of T-cell engagement: current state of CAR T cells and bispecific antibodies in B-cell lymphomas
In this Drug Advances article, Haydu and Abramson present an excellent summary of available data on chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies in large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. Hence, this comprehensive overview will serve many lymphoma physicians who need to review the pivotal trials and the current state-of-the-art management of this patient population.1
CAR T-cell toxicities: from bedside to bench, how novel toxicities inform laboratory investigations
Although there are numerous reviews on well-established CAR T-cell toxicities, this review article by Perna et al provides a comprehensive overview of novel/emergent CAR T-cell toxicities in hematologic and solid tumors for which there is scant literature. In addition, this review illustrates rare, unusual, and often unexpected toxicities in early clinical trials or in real-world setting that were not observed in preclinical studies. Exploratory findings, such as the role of the tumor microenvironment and intestinal microbiota in immune dysregulation and CAR T-cell toxicities, are also reviewed.2
Early predictive factors of failure in autologous CAR T-cell manufacturing and/or efficacy in hematologic malignancies
In this review article, Baguet et al discuss predictive factors that influence the manufacturing failures and successes of CAR T cells and the clinical response of CAR T-cell therapy, which may be helpful for early therapeutic decision-making for patients with hematologic malignancies.3
Infections following bispecific antibodies in myeloma: a systematic review and meta-analysis
The next article we selected was a systematic review and meta-analysis by Reynolds et al of published bispecific antibody trials for myeloma. The goal of the systematic review was to quantify the rates of infections and describe the infections reported in different clinical trials. Moreover, the review highlights the immunology of patients receiving bispecific antibodies and the clinical prophylaxis and management of these patients.4
Nivolumab for relapsed/refractory classical Hodgkin lymphoma: 5-year survival from the pivotal phase 2 CheckMate 205 study
In this report by Ansell et al, the authors report the 5-year follow-up of the CheckMate 205 study that enrolled patients with relapsed/refractory (R/R) classical Hodgkin lymphoma for whom autologous hematopoietic cell transplantation had failed. The patients received nivolumab in the phase 2 CheckMate 205 trial, and even at 5 years, the data continue to support the efficacy and safety of nivolumab with a favorable overall survival in this setting.5
Transient responses and significant toxicities of anti-CD30 CAR T cells for CD30+ lymphomas: results of a phase 1 trial
In this original article, Brudno et al report on the safety and efficacy of CD30 CAR T cells in patients primarily with classical Hodgkin lymphoma (1 patient with anaplastic large-cell lymphoma). The study reported lower response rates than expected and higher toxicities, with clinically significant rash and prolonged cytopenias leading to infection, which ultimately resulted in the discontinuation of this trial.6
Durable immunity to EBV after rituximab and third-party LMP-specific T cells: a Children’s Oncology Group study
This report by Wistinghausen et al shows durable latent membrane protein (LMP)–specific cytotoxic T-lymphocyte responses in newly diagnosed pediatric patients with posttransplant lymphoproliferative disease after an incomplete response to rituximab. This is, to our knowledge, the first “novel cell therapy study” conducted in a cooperative group, thereby confirming the feasibility of treating patients in this setting.7
Reinfusion of CD19 CAR T cells for relapse prevention and treatment in children with acute lymphoblastic leukemia
In this original article by Myers et al, the authors report the Children’s Hospital of Philadelphia’s experience of reinfusing murine or humanized 4-1BB CD19 CAR T cells into children with acute lymphoblastic leukemia who had already received 1 dose of CAR T cells. Specifically, they evaluated the persistence of CAR T cells in vivo when reinfusing these products to prevent or treat CD19+ relapsed disease and also evaluated clinical responses, including toxicities and antitumor effects.8
Safety and feasibility of third-party cytotoxic T lymphocytes for high-risk patients with COVID-19
This original article by Grosso et al demonstrates that severe acute respiratory syndrome coronavirus 2–specific cytotoxic T lymphocytes are well tolerated at all 4 doses tested in high-risk ambulatory adults, with >99% viral elimination in all patients by 2 weeks.9
Clinical features of neurotoxicity after CD19 CAR T-cell therapy in mantle cell lymphoma
Although CD19 CAR T cells are highly effective for treating R/R mantle cell lymphoma, immune effector cell–associated neurotoxicity syndrome (ICANS) remains an appreciable concern. In this study by Nie et al, the authors evaluated the clinical, laboratory, and radiological correlatives associated with ICANS in this setting.10
CD70-specific CAR NK cells expressing IL-15 for the treatment of CD19-negative B-cell malignancy
This study by Guo et al evaluated the preclinical efficacy of the CD70-specific CAR natural killer (NK)–cell product coexpressing interleukin-15 (IL-15). The authors show that this product has potent antilymphoma activity in multiple in vitro and in vivo models, indicating that CD70 may be an attractive target for the treatment of CD19– B-cell malignancies.11
The race is on: bispecifics vs CAR T cells in B-cell lymphoma
In this Commentary by Gurumurthi et al, the authors acknowledge that the treatment paradigm for R/R indolent and aggressive B-cell lymphomas has dramatically changed over the past 5 to 10 years. With the development and commercialization of bispecific T-cell–engaging antibodies (BiAbs) and autologous CAR T cells, there is much discussion in the field regarding the role of BiAbs vs CAR T-cell therapy in R/R lymphoma. This Commentary provides a comprehensive overview of the data and discusses some of the key questions that physicians face when having to choose between these 2 treatment modalities.12
Answering the “Doctor, can CAR-T therapy cause cancer?” question in clinic
In this Commentary, Banerjee et al address the “elephant in the room” after the FDA announcement regarding a small number of cases of T-cell second primary malignancies in the setting of CD19 and B-cell maturation CAR T-cell therapies. This Commentary is timely because, in January 2024, the FDA determined that the serious risk of T-cell malignancies is applicable to all currently approved B-cell maturation antigen– and CD19-directed autologous CAR T-cell products and concluded that changes to the boxed warning are warranted to highlight this risk.13
In summary, we continue to be excited by the upward trajectory of Blood Advances and the prominence of the journal in the field of hematology. We thank you for the privilege to lead the journal and are extremely grateful to all of our authors and reviewers. In addition, we extend our gratitude to the team at ASH headquarters whose dedication has been invaluable in shaping the journal into what it is today. Finally, Blood Advances is your journal, and it is only with your support that we can continue to grow the content. We sincerely thank you and welcome your suggestions regarding topic areas that may be of interest to you and the field.
Conflict-of-interest disclosure: For Wistinghausen et al7, C.M.B. is a cofounder and scientific advisory board member of Mana Therapeutics and Catamaran Bio; board member of Cabaletta Bio; has stock in NexImmune and Repertoire Immune Medicines; serves as a data safety monitoring board member for Sobi; and has served on advisory boards for Pfizer, Bristol Myers Squibb, and Roche. A.S.W. declares no competing financial interests.
