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CHRONIC LYMPHOCYTIC LEUKEMIA

Depth of response and progression-free survival in chronic lymphocytic leukemia patients treated with ibrutinib

Leukemia volume 36, pages 2129–2131 (2022)Cite this article

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Recent advances in therapeutics for the treatment of chronic lymphocytic leukemia (CLL) patients have revolutionized the field and have led to a variety of frontline options including Bruton tyrosine kinase inhibitors (BTKis) with or without obinutuzumab and BCL-2 targeting therapeutics (venetoclax) with obinutuzumab [1]. Correlation of depth of response with progression-free survival (PFS) has been well studied in patients undergoing treatment with both traditional chemoimmunotherapy and venetoclax-based regimens, with attainment of complete response (CR) or undetectable minimal residual disease associated with improved PFS [2, 3]. However, depth of response has not been correlated with PFS during treatment with the BTKi ibrutinib with or without monoclonal antibody therapy, and it is difficult to do so as it can take years for maximal response to be reached in patients receiving treatment with ibrutinib. We sought to assess whether response at one year could predict long-term PFS in CLL patients on treatment with ibrutinib, with the goal of identifying patients who could trial discontinuation of ibrutinib in the future.

We performed a retrospective analysis of CLL patients enrolled in 4 sequential clinical trials at the Ohio State University of ibrutinib as monotherapy or in combination with ofatumumab. Patients were treated with single-agent ibrutinib on OSU10032/Pharmacyclics (PCYC) 1102 (NCT01105247) [4], OSU 11133 (NCT01589302) [5], and OSU12024/RESONATE (NCT01578707) [6]. They were treated with combination ibrutinib and ofatumumab on OSU10053/PCYC 1109 (NCT01217749) [7].

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Fig. 1: Progression Free Survival.

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Funding

The study is funded in part through R01CA177292, R35CA197734, the D Warren Brown Foundation, and Pelotonia. JAW and KAR are Scholars of the Leukemia and Lymphoma Society.

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Author notes

  1. John C. Byrd

    Present address: Department of Internal Medicine, The University of Cincinnati, Cincinnati, OH, USA

Authors and Affiliations

  1. Division of Hematology, The Ohio State University, Columbus, OH, USA

    Audrey M. Sigmund, Ying Huang, Amy S. Ruppert, Kami Maddocks, Kerry A. Rogers, Samantha Jaglowski, Seema A. Bhat, Adam S. Kittai, Michael R. Grever, John C. Byrd & Jennifer A. Woyach

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  1. Audrey M. Sigmund
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Contributions

AMS and JAW designed the study; AMS and JAW collected the data; YH performed statistical analyses; YH confirmed the accuracy of the data and compiled it for analysis; and all authors were involved in manuscript preparation and approved the final version prior to submission.

Corresponding author

Correspondence to Jennifer A. Woyach.

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Competing interests

KM has consulted with Acerta, AstraZeneca, Pharmacyclics, Beigene, Loxo, Lilly, Genentech, Morphosys, Celgene, BMS, Kite. KAR received research funding from Genentech, AbbVie, and Janssen, consulted for Acerta Pharma, AstraZeneca, Innate Pharma, AbbVie, Genentech, Pharmacyclics, and Beigene, and received travel funding from AstraZeneca. SJ has consulted for Kite, Novartis, Juno, Takeda, CRISPR Therapeutics and has received research funding from Kite, Novartis, Juno, Caribou. ASK has consulted for Abbvie, Beigene, Bristol-Myers Squibb, and Janssen. MRG has received consult funding from Pharmacyclics, Astra Zeneca, Ascerta and Axio. JCB has consulted with Acerta, AstraZeneca, Pharmacyclics, Astellas, Syndax, and Jazz Pharmaceuticals and has stock ownership in Vincerx Pharmaceutics. JAW has consulted with Abbvie, AstraZeneca, Beigene, Janssen, Pharmacyclics, Loxo, and Newave, receives research funding from Morphosys, Karyopharm, Pharmacyclics, Janssen, and Schrodinger.

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Sigmund, A.M., Huang, Y., Ruppert, A.S. et al. Depth of response and progression-free survival in chronic lymphocytic leukemia patients treated with ibrutinib. Leukemia 36, 2129–2131 (2022). https://doi.org/10.1038/s41375-022-01640-y

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