Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

CHRONIC LYMPHOCYTIC LEUKEMIA

Clinicobiological characteristics and treatment efficacy of novel agents in chronic lymphocytic leukemia with IGLV3-21R110

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Clinicobiological profile of IGLV3-21R110 CLL.

References

  1. Hengeveld PJ, Levin MD, Kolijn PM, Langerak AW. Reading the B-cell receptor immunome in chronic lymphocytic leukemia: revelations and applications. Exp Hematol. 2021;93:14–24.

    Article  CAS  Google Scholar 

  2. Agathangelidis A, Chatzidimitriou A, Gemenetzi K, Giudicelli V, Karypidou M, Plevova K, et al. Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL. Blood. 2021;137:1365–76.

    Article  CAS  Google Scholar 

  3. Sutton LA, Young E, Baliakas P, Hadzidimitriou A, Moysiadis T, Plevova K, et al. Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors. Haematologica. 2016;101:959–67.

    Article  CAS  Google Scholar 

  4. Jaramillo Sonia, Agathangelidis Andreas, Schneider Christof, Bahlo Jasmin, Robrecht Sandra, Tausch Eugen, et al. Prognostic impact of prevalent chronic lymphocytic leukemia stereotyped subsets: analysis within prospective clinical trials of the German CLL Study Group (GCLLSG). Haematologica. 2019;105:2598–607.

    Article  Google Scholar 

  5. Maity PC, Bilal M, Koning MT, Young M, Van Bergen CAM, Renna V, et al. IGLV3-21∗01 is an inherited risk factor for CLL through the acquisition of a single-point mutation enabling autonomous BCR signaling. Proc Natl Acad Sci USA. 2020;117:4320–7.

    Article  CAS  Google Scholar 

  6. Nadeu F, Royo R, Clot G, Duran-Ferrer M, Navarro A, Martín S, et al. IGLV3-21R110 identifies an aggressive biological subtype of chronic lymphocytic leukemia with intermediate epigenetics. Blood. 2021;137:2935–46.

    Article  CAS  Google Scholar 

  7. Minici C, Gounari M, Übelhart R, Scarfò L, Dühren-von Minden M, Schneider D, et al. Distinct homotypic B-cell receptor interactions shape the outcome of chronic lymphocytic leukaemia. Nat Commun. 2017;8:1–12.

    Article  Google Scholar 

  8. Kolijn PM, Saberi Hosnijeh F, Späth F, Hengeveld PJ, Agathangelidis A, Saleh M, et al. High-risk subtypes of chronic lymphocytic leukemia are detectable as early as 16 years prior to diagnosis. Blood. 2021;139:1557–63.

    Article  Google Scholar 

  9. Kolijn PM, Muggen AF, Ljungström V, Agathangelidis A, Wolvers-Tettero ILM, Beverloo HB, et al. Consistent B cell receptor immunoglobulin features between siblings in familial chronic lymphocytic leukemia. Front Oncol. 2021;11:1–11.

    Article  Google Scholar 

  10. Kersting S, Dubois J, Nasserinejad K, Dobber JA, Mellink C, van der Kevie-Kersemaekers A-MF, et al. Venetoclax consolidation after fixed-duration venetoclax plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (HOVON 139/GiVe): primary endpoint analysis of a multicentre, open-label, randomised, parallel-group, phase 2 trial. Lancet Haematol. 2022;9:e190–9.

    Article  Google Scholar 

  11. Levin MD, Kater A, Mattsson M, Kersting S, Ranti J, Thi Tuyet Tran H, et al. Protocol description of the HOVON 141/VISION trial: A prospective, multicentre, randomised phase II trial of ibrutinib plus venetoclax in patients with creatinine clearance ≥30 mL/min who have relapsed or refractory chronic lymphocytic leukaemia (RR-CLL). BMJ Open. 2020;10:1–5.

    Article  Google Scholar 

  12. Niemann CU, Dubois J, Kersting S, Enggaard L, Veldhuis GJ, Mous R, et al. Venetoclax and ibrutinib for patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) - 15-month safety, response and mrd evaluation: third interim analysis from the phase II vision HO141 trial. Blood. 2019;134:4292–4292.

    Article  Google Scholar 

  13. Leeksma AC, Baliakas P, Moysiadis T, Puiggros A, Plevova K, van der Kevie-Kersemaekers AM, et al. Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: A multi-center study. Haematologica. 2020;105:87–97.

    Article  Google Scholar 

  14. Darzentas N, Hadzidimitriou A, Murray F, Hatzi K, Josefsson P, Laoutaris N, et al. A different ontogenesis for chronic lymphocytic leukemia cases carrying stereotyped antigen receptors: Molecular and computational evidence. Leukemia. 2010;24:125–32.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank all patients, their families, and investigators involved in the HOVON-139/GIVE and HOVON-141/VIsion trials. In addition, the authors would like to acknowledge Mr. Jorn Assmann and Miss. Lina van der Straten for their participation in constructive discussions that have significantly improved the manuscript.

Funding

The HOVON-139/GIVE trial was funded by F Hoffmann-La Roche (ML29995), who had the opportunity to review and comment on this paper. The HOVON-141/VIsion trial was supported by AbbVie and Janssen/Pharmacyclics, who had the opportunity to review and comment on this paper. In addition, the HOVON-141/VIsion trial was funded by the Novo Nordisk Foundation grant NNF160C0019302.

Author information

Authors and Affiliations

Authors

Contributions

PJH, MDL, and AWL conceived of the study. PJH and YEE performed the light chain sequencing. JMND, SK, CUN, APK, and MDL were involved in designing, operating and biobanking the HOVON-139/GIVE and/or HOVON-141/VIsion trials and facilitated the availability of the samples. CHMM, AMvdKK, ORFM, and MMM performed and analyzed the genomic array and targeted NGS analysis. LME performed the heavy-chain sequencing. KH assisted in primer design. PMK contributed to the data analysis. PJH, MDL, AWL, PMK, and PEW interpreted and reviewed the data. PJH, MDL, and AWL wrote the manuscript. All authors critically read and approved the final version of the manuscript.

Corresponding author

Correspondence to Mark-David Levin.

Ethics declarations

Competing interests

SK has received personal fees from Janssen, AbbVie, Novartis, Gilead, and Celgene; and research funding from AbbVie, Janssen, AstraZeneca, and Roche/Genentech. CUN received research funding and/or consultancy fees from Abbvie, AstraZeneca, Roche, Janssen, CSL Behring, Takeda, and Octapharma. APK has received personal fees from AbbVie, LAVA, Genmab, Janssen, AstraZeneca, Roche/Genentech, and Bristol Myers Squibb; and research funding from AbbVie, Janssen, AstraZeneca, Roche/Genentech, and Bristol Myers Squibb. AWL has received research support via an unrestricted grant from Roche-Genentech and a speaker-fee from Janssen. M-DL has received personal fees from AbbVie, Janssen, and Roche; and research funding from AbbVie, Janssen, AstraZeneca, and Roche/Genentech. All other authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hengeveld, P.J., Ertem, Y.E., Dubois, J.M.N. et al. Clinicobiological characteristics and treatment efficacy of novel agents in chronic lymphocytic leukemia with IGLV3-21R110. Leukemia 36, 1935–1938 (2022). https://doi.org/10.1038/s41375-022-01600-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41375-022-01600-6

This article is cited by

Search

Quick links