Page 252 - 2021_06-Haematologica-web

Letters to the Editor
regulated depending on the cell type or tumor microenvi- ronment. This would partly explain why other lym- phomas, albeit with high CD30 expression, are not as responsive as Hodgkin lymphoma and systemic anaplas- tic large cell lymphoma, as evident from recent studies, thereby showing no clear relation between CD30 expres- sion and clinical response.9-11 Conversely, even if CD30 expression was very low, tumor response was observed. Furthermore, tumor heterogeneity or unrevealed mecha- nisms of resistance may also contribute to the irrelevance of CD30 expression and efficacy of brentuximab vedotin. A recent study demonstrated that A20 negatively regu- lates the NF-kB pathway, and upregulation of NF-kB activity mediates resistance to brentuximab vedotin in Hodgkin lymphoma cell lines.15 In this study, targeted sequencing of paired tumor tissues revealed CARD11 and TRAF3 mutations related to constitutive NF-kB activa- tion, and the mutations were identified as possible resist- ance mechanisms to brentuximab vedotin.
In conclusion, brentuximab vedotin alone demonstrat- ed significant and durable clinical activity with a manage- able toxicity profile in relapsed or refractory EBV-positive and CD30-positive non-Hodgkin lymphomas. However, the results of this study, including correlative outcomes, should be interpreted cautiously because of the small number of patients, the single-arm design as well as the heterogeneous group of diseases. Thus, brentuximab vedotin warrants further investigational study, either as monotherapy or in combination, on a larger scale in this patient population.
Miso Kim,1,2 Jeong-Ok Lee,3 Jiwon Koh,4 Tae Min Kim,1,2 Ji Yun Lee,3 Yoon Kyung Jeon,2,4 Bhumsuk Keam,1,2 Dong-Wan Kim,1,2 Jong Seok Lee3 and Dae Seog Heo1,2
1Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; 2Seoul National University Cancer Research Institute, Seoul, Republic of Korea; 3Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea and 4Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea.
Correspondence: TAE MIN KIM - gabriel9@snu.ac.kr doi:10.3324/haematol.2021.278301
Received: January 8, 2021.
Accepted: March 11, 2021.
Pre-published: April 1, 2021.
Disclosures: TMK received a research grant from AstraZeneca-KHIDI not related to this work. DWK received travel and accommodation support for advisory board meeting attendance from Amgen and Daiichi-Sankyo not related to this work. All other authors declare that they have no competing interests.
Contributions: TMK designed the study; MK and TMK wrote
the manuscript; YKJ did the pathological review. All authors provided study materials or patients, contributed to the collection and assembly of data, data analysis, and interpretation, and reviewed and approved the final draft of the manuscript.
Acknowledgments: we thank the patients who participated in this trial and their families. We also thank Soyeon Kim, Ph.D., Sujung Huh, and Daye Paek for their contribution to the soluble CD30 experiments and Seonah Ha, Ph.D., who assisted in medical writing. Statistical analyses were supported by the Medical Research Collaborating Center (MRCC), Seoul National University, Seoul, Korea.
Funding: this study was funded by Takeda Pharmaceuticals Co, Ltd. and supported by a grant from the Korean Health Technology R&D Project "Strategic Center of Cell and Bio Therapy for Heart, Diabetes & Cancer” through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare (MHW) (grant number: HI-17C-2085).
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