Page 191 - Haematologica Vol. 109 - July 2024

ARTICLE - Disease burden of idiopathic MCD
M. Sarmiento Bustamante et al.
having both. Conversely, our strict inclusion criteria might have inadvertently excluded true iMCD patients who also developed malignancies.
This study has several limitations. First, 13 patients with the NOS subtype met the criteria for idiopathic plasmacytic lymphadenopathy (thrombocytosis and hypergammaglob- ulinemia) and may represent a distinct subtype from other iMCD-NOS patients.27 Due to the low number of patients and the similar, more moderate presentation, these patients were combined with other non-TAFRO patients in the NOS category.13 Second, our study included a larger proportion of TAFRO patients than NOS patients, so may not be repre- sentative of the whole iMCD population. To address this, we stratified our analyses between TAFRO and NOS subtypes. It is possible that the higher number of TAFRO patients in this study is a result of patients with more severe disease being more likely to seek resources online and thus enroll into the ACCELERATE registry. However, the study design for our registry is biased towards patients who survive and who are able to enroll themselves into a registry compared to patients who die shortly after diagnosis and would need a family member to enroll them.
Ultimately, our data demonstrate that an iMCD diagnosis imparts a long-term burden of disease on patients which results in high rates of hospitalization, the development of life-threatening iMCD-related morbidities and comorbidities requiring intensive interventions, and reduced QOL from active symptoms. These data demonstrate the importance of ongoing research into iMCD, the need to recognize and diagnose iMCD sooner, and the relevance of focused efforts to identify diagnostic and/or disease biomarkers to aid in disease management.
Disclosures
DCF has received research funding for the ACCELERATE registry, consulting fees from EUSA Pharma and study drug with no associated research funding for the clinical trial of sirolimus from Pfizer (NCT03933904); he has two provisional patents pending related to the diagnosis and treatment of iMCD. GS has received speakers’ bureau fees from Takeda, Janssen Pharmaceuticals, Foundation Medicine, and EUSA Pharma. AB has served on a EUSA Pharma Castleman disease advisory board. DA has served on the Castleman disease medical advisory board for EUSA Pharma and from 03/2023 to present serves as the advisory board’s co-chair. JDB has received consulting fees from EUSA Pharma. FvR has re- ceived consulting fees from EUSA Pharma, GlaxoSmithKline, Karyopharm, and Takeda and has received research funding
References
1. Beck JT, Hsu SM, Wijdenes J, et al. Brief report: alleviation of systemic manifestations of Castleman’s disease by monoclonal anti-interleukin-6 antibody. N Engl J Med. 1994;330(9):602-605.
from Janssen Pharmaceuticals and Bristol Myers Squibb. MJL serves on advisory boards for EUSA Pharma and Secura Bio, Inc., serves as an honorarium speaker for Southeastern Lymphoma Symposium, and receives consulting fees from the University of Pennsylvania. All other authors report no conflicts of interest.
Contributions
MSB was responsible for the formal analysis, writing the original draft as well as reviewing and editing the paper and visualization. SKP conceived the study and was respon- sible for the formal analysis, writing the original draft as well as reviewing and editing the paper and visualization. YR was responsible for the formal analysis, and wrote, reviewed and edited the paper. AB, JDB, GS, DA, MJL, HL, FvR, and MSL provided supervision and were involved in writing, reviewing and editing the paper. NM conducted investigations and was involved in writing, reviewing and editing the paper. DCF conceived and supervised the study, acquired funding and was involved in writing, reviewing and editing the paper.
Acknowledgments
The authors thank all the patients and their families for their participation in the ACCELERATE registry. We also thank the Castleman Disease Collaborative Network (CDCN) and the ACCELERATE Registry team for their support. We thank the volunteers for the CDCN who have supported this research, including Mary Zuccato and Mileva Repasky. We also thank Shawnee Bernstein, Nathan Hersh, Gerard Hoeltzel, and Jeremy Zuckerberg for their contributions to this study. Fi- nally, we thank Faizaan Ahkter, Erin Napier, Eric Haljasmaa, Katherine Floess, Mark-Avery Tamakloe, Victoria Powers, Alexander Gorzewski, Johnson Khor, Reece Williams, Jasira Ziglar, Amy Liu, Saishravan Shyamsundar, Criswell Lavery, and Bridget Austin.
Funding
The ACCELERATE natural history registry has received funding from Janssen Pharmaceuticals (2016-2018), EUSA Pharma, LLC (USA), which has merged with Recordati Rare Diseases Inc. (2018-2022), and the U.S. Food & Drug Administration (R01FD007632) (2022-Present). DCF also receives fund- ing from the National Heart, Lung, and Blood Institute (R01HL141408) (2018-present).
Data-sharing statement
All source data reported in this study are available by con- tacting the ACCELERATE team at accelerate@uphs.upenn.edu.
2. Yoshizaki K, Matsuda T, Nishimoto N, et al. Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman’s disease. Blood. 1989;74(4):1360-1367.
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