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Nature communications
Mar 30, 2024;15 (1): 2776.

Combination of acalabrutinib with lenalidomide and rituximab in relapsed/refractory aggressive B-cell non-Hodgkin lymphoma: a single-arm phase II trial.

Changhee Park, Ho Sup Lee, Ka-Won Kang, Won-Sik Lee, Young Rok Do, Jae-Yong Kwak, Ho-Jin Shin, Sung-Yong Kim, Jun Ho Yi, Sung-Nam Lim, Jeong-Ok Lee, Deok-Hwan Yang, Hun Jang, Byoungsan Choi, Jiwoo Lim, Choong Hyun Sun, Ja Min Byun, Sung-Soo Yoon, Youngil Koh
Author Information
  1. Changhee Park: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. ORCID
  2. Ho Sup Lee: Department of Internal Medicine, Kosin University College of Medicine, Gospel Hospital, Pusan, Republic of Korea.
  3. Ka-Won Kang: Department of Internal Medicine, Korea University College of Medicine, Anam Hospital, Seoul, Republic of Korea. ORCID
  4. Won-Sik Lee: Department of Internal Medicine, Busan Paik Hospital, Pusan, Republic of Korea.
  5. Young Rok Do: Department of Internal Medicine, Keimyung University Dongsan Medical Center, Daegu, Republic of Korea.
  6. Jae-Yong Kwak: Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Republic of Korea. ORCID
  7. Ho-Jin Shin: Department of Internal Medicine, School of Medicine, Pusan National University, Pusan, Republic of Korea.
  8. Sung-Yong Kim: Department of Internal Medicine, Department of Hematology/Oncology, KonKuk University Hospital, KonKuk University, Seoul, Republic of Korea.
  9. Jun Ho Yi: Department of Internal Medicine, Division of Hematology-Oncology, Department of Medicine, Chung-Ang University, Seoul, Republic of Korea.
  10. Sung-Nam Lim: Department of Internal Medicine, Department of Hematology-Oncology, Inje University Haeundae Paik Hospital, Pusan, Republic of Korea.
  11. Jeong-Ok Lee: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
  12. Deok-Hwan Yang: Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea. ORCID
  13. Hun Jang: Department of Biomarker Discovery, PROTEINA Co., Ltd, Seoul, Republic of Korea.
  14. Byoungsan Choi: Department of Biomarker Discovery, PROTEINA Co., Ltd, Seoul, Republic of Korea.
  15. Jiwoo Lim: GenomeOpinion Inc., Seoul, Republic of Korea.
  16. Choong Hyun Sun: GenomeOpinion Inc., Seoul, Republic of Korea.
  17. Ja Min Byun: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. ORCID
  18. Sung-Soo Yoon: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. ORCID
  19. Youngil Koh: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea. go01@snu.ac.kr. ORCID
PMID: 38555311 DOI: 10.1038/s41467-024-47198-4

Abstract

Potential synergism between Bruton's tyrosine kinase (BTK) inhibitor and lenalidomide in treating aggressive B-cell lymphoma has been suggested. Here, the authors report a single-arm phase II clinical trial of combination of acalabrutinib, lenalidomide and rituximab (R2A) in patients with aggressive relapsed/refractory aggressive (R/R) B-cell non-Hodgkin lymphoma (NHL). The primary endpoint of this study is objective response rate (ORR), and the secondary endpoints are complete remission (CR) rate, duration of response (DoR), progression-free survival (PFS) and overall survival (OS). A total of 66 patients are enrolled mostly with diffuse large B-cell lymphoma. The ORR is 54.5% and CR rate is 31.8% meeting the primary end point. The median DoR is 12.9 months, and 1-year PFS and OS rate is 33.1% and 67.5% respectively. Adverse events (AE) are manageable with the most frequent AE being neutropenia (31.8%). Patients with MYD88 mutations, subtypes known for NF-κB activation, and high BTK expression by immunohistochemistry respond well. Overall, these results show a significant efficacy of the R2A regimen in patients with aggressive R/R B-cell NHL, with exploratory biomarkers suggesting potential associations with response. (ClinicalTrials.gov 51 identifier: NCT04094142).

Associated Data

ClinicalTrials.gov | NCT04094142

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Grants

  1. ESR-18-13701/AstraZeneca Korea

MeSH Term

Humans
Antineoplastic Combined Chemotherapy Protocols
Benzamides
Disease-Free Survival
Lenalidomide
Lymphoma, Large B-Cell, Diffuse
Pyrazines
Rituximab
Treatment Outcome

Chemicals

acalabrutinib
Benzamides
Lenalidomide
Pyrazines
Rituximab
Clinical Trial, Phase II Journal Article
Article has an altmetric score of 3

Word Cloud

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